Burden of Disease, Treatment Patterns, and Healthcare Resource Utilization in Multiple Myeloma in the Middle East and North Africa Region: A Targeted Literature Review.

Key Summary Points

This literature review aims to understand the epidemiology and burden of disease, treatment patterns and availability, patient and clinical outcomes, and healthcare resource utilization (HCRU) in multiple myeloma (MM) in the Middle East and North Africa (MENA) region. Incidence of MM in the MENA region is increasing, with a median age at diagnosis younger than the global average. Many gaps exist in the published literature on treatment sequencing in the region, and in associated patient outcomes and HCRU. Articles inconsistently reported certain patient characteristics, such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB criteria); cytogenetic abnormalities; and adverse events associated with MM treatments.

Introduction

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by an abnormal increase in monoclonal immunoglobulins and bone marrow infiltration, leading to hematopoietic suppression and end-organ damage [ 1 ]. Symptomatic disease is defined by the SLiM (clonal bone marrow plasma cell percentage ≥ 60%, involved: uninvolved serum free light chain ratio ≥ 100, > 1 focal lesion on MRI) and CRAB criteria (hypercalcemia, renal insufficiency, anemia, and bone lesions), reflecting the systemic impact of monoclonal plasma cell proliferation [ 1 , 2 ]. With the availability of novel therapeutic options, MM is generally considered to be a treatable disease, but for the majority of patients, it is not yet curable [ 3 , 4 ]. The incidence of MM varies greatly across countries and regions [ 3 ]. Globally, MM accounts for 1–1.8% of all cancers and approximately 10% of hematological malignancies, and it is the cause of 1.2% of all cancer deaths [ 3 , 5 , 6 ]. In 2022, approximately 187,952 new cases of MM and 121,388 MM-related deaths were recorded worldwide [ 3 ]. Of these, 8457 new cases and 6753 deaths were reported in the North Africa and Central and Western Asia regions [ 3 ]. The incidence of MM is increasing in the Middle East and North Africa (MENA) region, where some countries have limited resources and the socioeconomic burden of the disease raises significant concerns [ 7 ].

The management of MM has advanced significantly over the past two decades with the approval of key drug classes, such as immunomodulatory imide drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies, which are now the standard of care in global treatment guidelines [ 5 ]. While initial treatment with these drugs has improved outcomes in patients with MM [ 8 – 10 ], the disease often becomes refractory, necessitating new therapies [ 8 , 11 , 12 ]. Recent approvals of novel agents—including antibody–drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor (CAR) T-cell therapy—have broadened treatment options for patients with relapsed and/or refractory MM (RRMM) [ 11 ]. However, multidrug combinations, while effective, increase the clinical and economic burden and have a considerable impact on patient quality of life (QOL)—particularly as RRMM typically requires prolonged treatment [ 13 ].

The MENA region often faces unique healthcare challenges, including substantial variability in resources and infrastructure. Improved understanding of healthcare resource utilization (HCRU) for MM may aid in optimizing resource allocation to improve the efficient use of limited resources [ 14 – 18 ]. Limited data exist on the availability and uptake of novel therapies, as well as the safety and effectiveness of these treatments in real-world practice in MENA. Obtaining further information on how these treatments are accessed and used is crucial to identifying and helping address specific challenges in the management of MM in the region.

This literature review aims to understand the epidemiology and burden of disease, treatment patterns and availability, patient and clinical outcomes, and HCRU in multiple myeloma in the MENA countries of Egypt, Saudi Arabia, Turkey, and the United Arab Emirates (UAE).

Methods

A comprehensive search strategy was developed, encompassing established practices for defining the literature search scope and agreement of search terms. The population, intervention, comparators, and outcomes framework was used to construct the research topics and criteria, and the bibliographical search strategy (Table S1 ). Broad search strings incorporating “Middle East or North Africa or MENA or Gulf region,” individual countries (“Egypt,” “Saudi Arabia,” “Turkey,” and “UAE”) and “multiple myeloma [MeSH]” were applied to capture articles and published major congress abstracts of relevance from PubMed and Embase published between 1 January 2015 and 31 May 2025 (Supplementary Table S2).

Article titles were screened initially for relevance, followed by abstracts. Full-text review and data extraction were conducted for included articles. Inclusion and exclusion criteria are presented in Supplementary Table S3. Disease epidemiology, patient characteristics, treatment patterns, clinical and patient-reported outcomes, and HCRU were summarized and analyzed by geography, line of therapy (LOT) and intervention—where data were available.

Results

A total of 1400 articles were identified in the PubMed and Embase databases (Fig. 1 ). Of these, 1202 were excluded by title/abstract screening, 168 full-text articles and conference abstracts were assessed for eligibility, and 94 (64 full-text publications and 30 conference abstracts) met the eligibility criteria for data extraction (Supplementary Table S4). Fig. 1 PRISMA diagram of articles included in this analysis

Most articles reported findings from retrospective observational studies (66/94; 70.2%). The articles most commonly reported findings from Turkey (52/94; 55.3%), followed by Saudi Arabia (17/94; 18.1%); eight studies reported on MENA as a region (8.5%), and five reported on the Gulf region (5.3%).

An additional four articles were added post hoc from a gray literature search: two Saudi Arabian treatment guidelines published after the literature search date, a treatment guideline from the Turkish Society of Hematology not indexed in PubMed or Embase and one report from the Saudi Cancer Registry.

Epidemiology of MM in the MENA Region

Incidence of MM

Six articles described the epidemiology of MM: four utilizing regional data from the International Agency for Research on Cancer’s (IARC) GLOBOCAN database (two reported on the incidence of MM in MENA, one in North Africa, and one on individual countries), one in Turkey, and one in Saudi Arabia (Fig. 2 a) [ 7 , 19 – 23 ]. Fig. 2 Incidence of MM in the MENA region. a Age-standardized incidence rate reported by geography and sex, where reported [ 7 , 19 – 23 ]; b age distribution of MM cases in Saudi Arabia reported in 2022 [ 24 ]. a MENA encompasses the countries of Afghanistan, Algeria, Bahrain, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Palestine, Qatar, Saudi Arabia, Sudan, Syrian Arab Republic, Tunisia, Turkey, the UAE, and Yemen. ASIR age-standardized incidence rate, MENA Middle East and North Africa, MM multiple myeloma, UAE United Arab Emirates

In the MENA region, the age-standardized incidence rate (ASIR) was 1.49 per 100,000 population in 2019, with a 14.95% change from 1990 to 2019 [ 7 ]. Most incident cases were in patients aged 50–70 years (53.87%), followed by > 70 years (33.00%); 13.14% of cases occurred in patients aged 15–49 years [ 7 ].

Data retrieved from the IARC GLOBOCAN database indicated an estimated 2827 incident cases in 2022 in North Africa, accounting for 1.5% of MM diagnoses globally, with an ASIR of 1.3 per 100,000 (1.6 in men, 1.0 in women) [ 20 ].

One study analyzed patients with MM who were treated within Turkey’s social insurance system (Sosyal Güvenlik Kurumu), and reported an average of 1300 incident cases of MM treated per year between 2011 and 2017, totaling 10,146 cases over this period [ 23 ]. The reported incidence of MM in this study was higher in men than in women, with 5655 and 4491 incident cases over this time period, respectively, and a median age at diagnosis between 63.8 and 66.1 years [ 23 ]. An analysis of the IARC GLOBOCAN database in 2020 reported an ASIR of 2.63 per 100,000 persons; notably, the incidence of MM in men significantly increased between 2001 and 2019 in Turkey, with an average annual percentage change (AAPC) of 5.63 (95% CI 1.12–10.35; p = 0.020); the increase in women was not statistically significant (AAPC: 3.28; 95% CI −0.88 to 7.61; p = 0.11) [ 21 ].

The ASIR of MM in Saudi Arabia was reported to be 1.02 per 100,000 persons in a study utilizing the GLOBOCAN database in 2020 [ 21 ]. This was lower than that reported by the Saudi Cancer Registry in 2022, which reported ASIRs of 2.3 and 1.4 per 100,000 men and women, respectively, among Saudi nationals in 2022 [ 24 ]. In 2022, there were 127 and 85 incident cases of MM in men and women, respectively, accounting for 1.5% and 0.8% of all cancer diagnoses in Saudi Arabia. Most cases occurred in people aged ≥ 50 years (0–49 years: 28 and 16 cases in men and women, respectively; 50 + years: 99 and 69 cases in men and women, respectively; Fig. 2 b) [ 24 ].

Huang and colleagues utilized the IARC database to retrieve data on MM in 2020 for individual countries [ 21 ]. From this analysis, the ASIRs for Egypt and UAE were 0.89 and 1.71 per 100,000 persons, respectively [ 21 ].

Presenting Symptoms

At presentation or study entry, CRAB criteria were commonly reported across the literature, with bone manifestation as one of the most commonly reported symptoms, occurring in 53.8–96.9% of patients. However, reporting differed across studies; some studies only reported average calcium, creatinine, or hemoglobin levels or glomerular filtration rates without reporting the proportion of patients who fit the definition of each of the CRAB symptoms. The definitions of the other criteria varied across the studies, and these differences in definitions and thresholds limited comparisons.

Patient Characteristics

Of the 69 real-world studies reporting patient age, the median age of study participants ranged from 43 to 70 years (Supplementary Table S4). For patients with newly diagnosed MM (NDMM; N = 13,083 from 23 studies), the median age of study participants ranged from 45 to 70 years; for patients with RRMM ( N = 1443 from 18 studies), the median age of study participants ranged from 49.6 to 69.5 years (Supplementary Table S4).

The sex distribution of MM was reported in 62 articles. Of the 17,477 patients included across these studies, 9778 (55.9%) were men; this trend was reflected in each of the individual countries, with 55.4–75.0% of patients reported to be men (Fig. 3 a). Fig. 3 Demographics and baseline disease characteristics of patients with MM in MENA. a Sex distribution of patients with MM; b ISS stage at diagnosis/study entry, where known/reported [ 23 , 25 – 28 , 30 – 35 , 37 , 39 – 42 , 50 , 51 , 53 – 57 , 59 – 65 , 67 – 70 , 72 – 75 , 77 – 81 , 117 – 128 ]. ISS International Staging System, MM multiple myeloma, NDMM newly diagnosed multiple myeloma, RRMM relapsed and/or refractory multiple myeloma, UAE United Arab Emirates

The International Staging System (ISS) stage at study entry or diagnosis was reported in 42 articles. Of the 5118 patients included across these studies, patients most commonly had ISS stage III disease (41.4%; range 7.4–86.8%), followed by stage II (32.6%; range 8.8–61.8%) and stage I (26.1%; range 0–81.5%) (Fig. 3 b). Of patients with NDMM, slightly more patients had stage III disease at study entry (37.2%) than stage I (29.8%) or II (33.0%); of patients with RRMM, most patients had stage II or III disease (39.1% and 41.6%, respectively). For individual countries, stage III disease was most common in patients in Saudi Arabia and Turkey (46.4% and 38.6%, respectively), while stage I disease was most common in Egypt (42.8%); one study reported ISS stage in patients in the UAE ( N = 32), where stage II disease was the most common disease stage at study entry (46.4%).

Cytogenetic abnormalities were reported in 25 studies; however, the abnormalities were inconsistently assessed and reported across the studies retrieved. The most commonly reported cytogenetic abnormalities were del(17p), del(13q), and t(4;14), reported in nine, eight, and eight studies, respectively.

Treatment Patterns

A total of 19 articles reported on real-world treatment usage in 12,200 patients with MM, where study entry was not determined by current or prior treatments [ 23 , 25 – 42 ]. The study period for most of these articles was after 2010, although one study analyzed patients treated between 1997 and 2015 in Saudi Arabia [ 25 ] and another between 1995 and 2020 in Turkey [ 39 ].

Overall, bortezomib was the most commonly used drug, with nearly half (49.7%) of all patients receiving a regimen that contained bortezomib. Regimens with lenalidomide (22.8%) and chemotherapy (13.2%) were the second and third most common (Fig. 4 a). Treatment patterns were largely similar across the individual countries of interest (Fig. 4 b–f), with most patients being treated with a regimen that contained bortezomib (49.3–100%). In Egypt, Turkey, and the UAE, lenalidomide was the second most common drug, with 16.7%, 22.7% and 66.7% of patients treated with a lenalidomide-containing regimen, respectively. In Saudi Arabia, chemotherapy was the second most common treatment (22.7%). Fig. 4 Real-world treatment patterns between 1995 and 2023 a reported in MENA, in a all patients in identified studies with data available; b patients with MM in the Gulf region; c patients with MM in Egypt; d patients with MM in Saudi Arabia; e patients with MM in Turkey; f patients with MM in the UAE; g patients with NDMM; and h patients with RRMM [ 23 , 25 – 42 ]. a Includes three studies with study periods encompassing 1997–2015, 1995–2020, and 2001–2018; the remaining studies report treatment usage from 2010 to 2023. b refers to chemotherapy regimens without protease inhibitors, immunomodulatory drugs, nor anti-CD38 antibodies, with or without steroids. MENA Middle East and North Africa, MM multiple myeloma, NDMM newly diagnosed multiple myeloma, RRMM relapsed/refractory multiple myeloma, UAE United Arab Emirates

Among patients with NDMM ( n = 11,152) (Fig. 4 g), nearly half (49.2%) of all patients were treated with a regimen containing bortezomib; the second most common drug was lenalidomide (23.5%) followed by chemotherapy (12.8%). In a retrospective registry study reporting real-world treatment patterns in patients with MM treated in tertiary-level care centers in the Gulf region who experienced relapse at least once between July 2020 and July 2022 (REPAIR study: N = 148, from Saudi Arabia, the UAE, Kuwait, and Qatar), first line (1L) induction treatments were generally similar between patients who did and did not receive autologous stem cell transplantation (ASCT), with most patients treated with a regimen containing bortezomib (47% and 42%, respectively) and/or lenalidomide (33% and 36%) (Supplementary Fig. S1 ) [ 27 ]. Thalidomide was the exception to this trend, being mainly used in patients who did not receive ASCT (4.4%) [ 27 ].

Of patients with RRMM ( N = 668) (Fig. 4 h), treatment regimens containing bortezomib were the most commonly used (51.6%), closely followed by daratumumab (44.5%), which was rarely used in patients with NDMM. In the REPAIR study, bortezomib was more frequently used in earlier LOTs: 47.3%, 12.5% and 4.3% of patients in 1L, second line (2L), and third line (3L), respectively (Supplementary Fig. S1 ) [ 27 ]. Patients receiving their second to fourth LOT were most commonly treated with daratumumab (24.2%), followed by carfilzomib (15.6%) and pomalidomide (15.0%) [ 27 ].

In a cross-sectional study in patients with NDMM within Turkey’s social insurance system ( N = 10,146, mostly treated in the public healthcare system) diagnosed between 2011 and 2017, lenalidomide use showed an increasing longitudinal trend: 235 of the 1168 (20.1%) patients diagnosed in 2011 were treated with lenalidomide compared with 787 of 1378 (57.1%) in 2017 [ 23 ]. Notably, in this study, lenalidomide was the most frequently used treatment in 2016 and 2017 [ 23 ]. A separate study of real-world treatment patterns in Turkey identified 107 patients with RRMM initiating 2L and 3L treatment, reporting that lenalidomide-containing regimens were used in 41.9% and 63.4% of patients, respectively. Overall, 53.1% of patients were retreated with lenalidomide in a later LOT and 30.8% were refractory to lenalidomide [ 36 ].

Of the studies that reported on real-world usage of treatment regimens in patients with MM ( N = 2061) reporting data from 1995 to 2023, bortezomib + cyclophosphamide + dexamethasone (VCd) was the most commonly used regimen (37.5%) followed by vincristine + doxorubicin + dexamethasone (VAD; 11.6%) (Supplementary Fig. S2). VCd was the most commonly used regimen (48.1%) in patients with NDMM ( N = 1255), while daratumumab + bortezomib + dexamethasone (DVd; 33.1%) was the most common regimen used in patients with RRMM ( N = 462). Quadruplet regimens were used in 0.92% of patients with MM (bortezomib + lenalidomide + dexamethasone + cyclophosphamide: 0.58%; daratumumab + lenalidomide + bortezomib + dexamethasone: 0.34%), and were only reported in the REPAIR study in patients with NDMM [ 27 ]. Of individual countries, VCd was the most commonly used regimen in Egypt, Saudi Arabia, and Turkey (35.3–59.3%). In the UAE, bortezomib + lenalidomide + dexamethasone (VRd) was the most common regimen (66.7%). According to the REPAIR study, VRd was the most frequently used regimen (27.1%) in the Gulf region in patients with MM [ 27 ]. For patients receiving their first, second, third, and fourth LOT, the most frequently used regimens were VRd (50.8%), DVd (17.2%), carfilzomib + pomalidomide + dexamethasone (18.5%), and pomalidomide + bortezomib + dexamethasone (20%), respectively [ 27 ].

Treatment Guidelines

Four treatment guidelines were identified within our literature search: two focusing on the management of NDMM and RRMM in the Gulf region [ 43 , 44 ], and two focusing on apheresis/ASCT in Turkey [ 45 , 46 ]. Recommendations on the management of RRMM developed by a group of MM experts in the Gulf region were also identified [ 22 ]. Treatment guidelines for the management of NDMM and RRMM in Saudi Arabia were published shortly after our literature search cutoff [ 47 , 48 ]; treatment guidelines from the Turkish Hematology Society were published in 2024 but not indexed in PubMed or Embase [ 49 ]. These were included as gray literature and recommendations from the guidelines are summarized in Table 1 . Table 1 Summary of MENA-specific treatment guidelines Gulf region a 2025 [ 43 , 44 ] Gulf region a expert recommendations 2025 [ 22 ] Saudi Arabia Myeloma Working Group 2025 [ 47 , 48 ] Turkish Society of Hematology 2024 [ 49 ] NDMM Transplant eligible • Induction with DVRd • Maintenance with lenalidomide, or daratumumab + lenalidomide in select patients (e.g., those who responded well to DVRd and are likely to tolerate continuous daratumumab + lenalidomide) – Standard risk • Quadruplet induction containing an anti-CD38 mAb (e.g., DVRd or Isa-VRd) followed by upfront ASCT or delaying ASCT until first relapse High risk • Anti-CD38 mAb + VRd followed by upfront ASCT Patients with organ failure/renal disease b • DVCd, with dose adjustment according to renal clearance. Once renal function improves, switching cyclophosphamide to lenalidomide is preferable Standard risk (induction) • Induction with a quadruplet regimen (DVRd, DVTd, or DVCd), DRd, VRd, VTd or VCd followed by ASCT if a ≥ VGPR is achieved, then maintenance therapy for at least 2 years High risk (induction) • Induction with a quadruplet regimen (DKRd, DVRd, DVTd, or DVC), D-KRCd, DRd, VRd, or KRd followed by ASCT if a ≥ VGPR is achieved, then maintenance therapy for at least 2 years After 4–6 cycles of induction therapy • Proceed to ASCT, followed by maintenance for > 2 years • If a ≥ VGPR/MRD-negativity is not achieved, consider a second consecutive ASCT Transplant ineligible • DRd until disease progression • For fit patients aged 65–70 years, 6–8 cycles of DRd followed by daratumumab + lenalidomide until disease progression. Patients may be able to progress to ASCT and should be considered in specific circumstances – Standard risk • Fit: DVRd or Isa-VRd followed by lenalidomide maintenance • Frail: DRd until progression or VRd followed by lenalidomide maintenance • Very frail: Vd/Rd or daratumumab + lenalidomide High risk • Fit: DVRd or IsaVRd for 9 cycles • Frail: DRd or VRd for 9 cycles Initial treatment • Non-frail: DRd, VRd/VRd-lite, VCd, Rd, VMP/DVMP, Isa-VRd • Frail: Rd, Vd, D-Ixa, MP, thalidomide, cyclophosphamide + dexamethasone After 2 cycles • If ≥ PR, continue on the same treatment • If < PR, consider changing treatment; if ≥ VGPR after 6–12 cycles, maintenance for > 2 years or until progression RRMM Early relapse Lenalidomide sensitive • DRd c Lenalidomide refractory • DKd; if an anti-CD38 mAb is not available/cannot be used, a carfilzomib approach is recommended, with KCd or KPd being the regimens of choice Guided by prior treatment and refractory status d Lenalidomide refractory • Anti-CD38 mAb-based, e.g., DPd or IsaKd Prior anti-CD38 mAb • Carfilzomib-based combinations, e.g., PomKd Bortezomib refractory but lenalidomide sensitive • DRd, KCd, PomKd Double refractory • DKd, IsaKd, IsaPd, PomKd, KCd First relapse : consider salvage ASCT in eligible patients who have not had a prior ASCT Lenalidomide sensitive • If not refractory to anti-CD38 mAb: DRd or IsaRd • If refractory to/relapse while on anti-CD38 mAb: KRd Lenalidomide refractory • If not refractory to anti-CD38 mAb: DKd, IsaKd, or PVd • If refractory to/relapse while on anti-CD38 mAb: PVd or PI + Cd Guided by prior treatment and refractory status e Late relapse • BsAb or CAR T-cell therapy for triple class–exposed patients • Selinexor should only be considered when there is no access to BsAbs or CAR T Triple refractory • CAR T-cell therapy Where conventional treatments are exhausted • Elranatamab Where transplant is not available • BsAb Transplant ineligible • Daratumumab monotherapy • DVRd Second or later relapse f : consider clinical trials or salvage ASCT in eligible patients who have not had a prior ASCT • Treatment regimens should be determined based on the patient’s previous therapies: if an anti-CD38 mAb has not been used and the patient is eligible, it should be included in the treatment plan • Refer patients for consideration of CAR T-cell therapy if high risk and poor response to quadruplet-based initial therapy Lenalidomide/bortezomib refractory • DKd, IsaPd, EloPd, IsaKd, DPd, Seli-Pd, Ven-Kd Lenalidomide refractory, PI sensitive • DKd, EloPd, IsaKd, IsaPd, DPd, DVd, Seli-Vd, Seli-Pd, Ven-Vd, Ven-Kd Triple refractory • Clinical trials • Seli-d, belamaf, melflufen-d, Ven, BsAb, CAR T ASCT autologous stem cell transplant, belamaf belantamab mafodotin, BsAb bispecific antibody, CAR chimeric antigen receptor, Cd cyclophosphamide + dexamethasone, DKd daratumumab + carfilzomib + dexamethasone, DPd daratumumab + pomalidomide + dexamethasone, DRd daratumumab + lenalidomide + dexamethasone, DVCd daratumumab + bortezomib + cyclophosphamide + dexamethasone, DVRd daratumumab + bortezomib + lenalidomide + dexamethasone, EloPd elotuzumab + pomalidomide + dexamethasone, IsaKd isatuximab + carfilzomib + dexamethasone, IsaPd isatuximab + pomalidomide + dexamethasone, IsaRd isatuximab + lenalidomide + dexamethasone, IsaVRd isatuximab + bortezomib + lenalidomide + dexamethasone, KCd carfilzomib + cyclophosphamide + dexamethasone, KPd carfilzomib + pomalidomide + dexamethasone, KRd carfilzomib + lenalidomide + dexamethasone, mAb monocloncal antibody, MM multiple myeloma, PomKd pomalidomide + carfilzomib + dexamethasone PI proteasome inhibitor, PVd pomalidomide + bortezomib + dexamethasone, Seli-d selinexor + dexamethasone, Seli - Pd selinexor + pomalidomide + dexamethasone, Seli-Vd selinexor + bortezomib + dexamethasone, Vd bortezomib + dexamethasone, Ven venetoclax, Ven-Kd venetoclax + carfilzomib + dexamethasone, Ven-Vd venetoclax + bortezomib + dexamethasone, Ven-Kd venetoclax + carfilzomib + dexamethasone a Gulf region refers to Kuwait, Oman, Qatar, and United Arab Emirates b Renal disease related to MM, defined as serum creatinine > 2 mg/dL or creatinine clearance < 40 mL/min c If the patient is young and fit, has an existing source of stem cells, and was in remission for > 4 years, a second ASCT can be considered d A second ASCT may be considered in transplant-eligible patients if they achieved > 36 months of remission after their initial ASCT e For patients treated with 1L VRd and lenalidomide sensitive: KRd, DRd, PVd, DPd, DKd, IsaPd, IsaKd, IxaRd, Seli-Vd, KCd, KPd, PCd, EloRd; lenalidomide refractory: PVd, DPd, DKd, IsaKd, IsaPd, Seli-Vd, KCd, KPd, PCd; bortezomib sensitive: KRd, DPd, DRd, EloRd, PVd, DKd, DVd, IsaKd, IsaPd, Seli-Vd, Ven-Vd, KCd, KPd, PCd; lenalidomide/bortezomib refractory: DKd, DPd, IsaKd, IsaPd, KCd, KPd, PCd. For patients treated with 1L DRd and lenalidomide sensitive: DKd, DPd, IsaKd, IsaPd, KCd, KPd, PCd; lenalidomide refractory: PVd, Kd, Seli-Vd, Seli-Pd, Ven-Vd, Ven-Kd, KCd, KPd, PCd. For patients treated with 1L DVTd or DVMP and bortezomib sensitive: EloRd, KRd, IxaRd, VRd, Seli-Vd, Seli-Pd, Kd, Ven-Vd, Ven-Kd, PVd; bortezomib refractory: EloRd, KCd, KPd, PCd, Seli-Pd, Ven-Kd f For patients without plasma cell leukemia or extramedullary disease

Clinical and Patient-Reported Outcomes

Clinical outcomes were reported in 60 articles, reporting a combination of response rates, progression-free survival (PFS), and overall survival (OS) (Table 2 ). Table 2 Patient and clinical outcomes Study Patient population Intervention/subpopulation N mPFS, months PFS rate, % mOS, months OS rate, % ORR, % CR, % VGPR, % PR, % NDMM Kim et al. [ 74 ] NDMM SCT 32 – – – – – 71.9 sCR: 15.6 6.3 6.3 Non-SCT 14 – – – – – 14.3 sCR: 7.1 14.3 14.3 Alhejazi et al. [ 27 ] NDMM First LOT 148 79.0 43.2 sCR: 4.7 17.6 13.5 Abdrabou et al. [ 64 ] NDMM VCd followed by ASCT 87 49 – – 5-year: 84 – Pre-ASCT: 31 Post-ASCT: 35.6 sCR: 6.9 (pre-ASCT) 16.1 (post-ASCT) Pre-ASCT: 41.4 Post-ASCT: 32.2 Pre-ASCT: 1.1 Post-ASCT: 0 Erdogan Yucel et al. [ 68 ] NDMM Age ≤ 65 years 115 44 – 78 – – – – – Age > 65 years 26 30 – 67 – – – – – Kazgı et al. [ 34 ] NDMM Patients with cytogenetic abnormalities 68 – – – – 60.3 – – – Kaloyannidis et al. [ 50 ] NDMM 116 – – NR 4-year: 67 8-year: 51 83 ≥ CR: 37 24 22 Abdrabou et al. [ 25 ] NDMM Pre-ASCT – – – – – – 38.1 sCR: 11.9 11.3 38.1 Post-ASCT – – – – – – 57.4 sCR: 20.7 11.8 6.5 Çiftçiler et al. [ 118 ] NDMM ASCT after induction therapy 153 – 5-year DFS: 46 – 5-year: 75 – – – – Mersin et al. [ 50 ] NDMM VCd with Velcade ® 42 – – – – 81 23.8 31 26.2 VCd with generic bortezomib 53 – – – – 79.2 18.9 20.8 39.6 Baysal et al. [ 29 ] NDMM Overall 159 – – 50 – – – – – 0 HRCA 126 – – 57 – – – – – 1 HRCA 24 – – 32 – – – – – 2 HRCAs 7 – – 6 – – – – – Çiftçiler et al. [ 65 ] NDMM Vd 36 67.1 5-year: 56 56 5-year: 75 – – ≥ VGPR Pre-ASCT: 19.4 Post-ASCT: 86.1 – VCd 67 97.7 5-year: 59 59 5-year: 83 – – ≥ VGPR Pre-ASCT: 29.9 Post-ASCT: 88.1 – Denewer et al. [ 66 ] NDMM with FISH available – 25 t(4;14): 36 Non-t(4;14): 88.5 del(17p): 23.3 Non del(17p): 52.9 t(11;14): 49.1 non-t(11;14): 41.1 del(13q): 20.7 Non del(13q) 51.0 – t(4;14): 36 Non-t(4;14): 85.0 del(17p): 35.5 Non del(17p): 81.0 t(11;14): 93 non-t(11;14): 48.1 del(13q): 35.0 Non del(13q) 77.8 – – – – – Ciftciler et al. [ 30 ] NDMM ASCT (patients with CR/VGPR pre-ASCT) 47 – – – – – – ≥ VGPR: 95.7 – ASCT (patients with ≤ PR pre-ASCT) 157 ≥ VGPR: 85.4 Abdelgawad et al. [ 63 ] NDMM – 89 mDFS: 12 5-year DFS: 45.7 – 5-year: 72.7 – – – – Abduljalil et al. [ 129 ] NDMM – 63 – 95-month rate: 41.1 – 95-month rate: 69.1 – – – – El-Ghammaz et al. [ 67 ] Standard risk NDMM with no del(17p) and/or t(4;14) VAD induction followed by high-dose melphalan and ASCT 27 26 At DCO: 77.8 NR At DCO: 92.6 – Post-ASCT: 77.8 – – Vd induction followed by high-dose melphalan and ASCT 27 31 At DCO: 85.2 NR At DCO: 96.3 – Post-ASCT: 85.2 – – High risk NDMM with del(17p) and/or t(4;14) VAD induction followed by high-dose melphalan and ASCT 13 20 At DCO: 23.1 22 At DCO: 53.8 – Post-ASCT: 23.1 – – Vd induction followed by high-dose melphalan and ASCT 13 NR At DCO: 69.2 NR At DCO: 69.2 – Post-ASCT: 69.2 – – RRMM Alhejazi et al. [ 27 ] RRMM Second LOT 139 – – – – 62.2 33.1 sCR: 2.9 13.0 10.1 Third LOT 55 – – – – 45.7 16.0 sCR: 1.8 12.9 15.0 Fourth LOT 16 – – – – 12.7 6.2 sCR: 0 6.2 0 Öztürk et al. [ 127 ] RRMM Allo-SCT 30 – – – 1-year: 45 2-year: 36.3 3-year: 31.7 – – – – Açar et al. [ 52 ] RRMM (≥ 2 prior LOT) BPd 11 – 2-year: 71.3 23 2-year: 81.8 54 9.1 45.4 18.2 Bakırtaş et al. [ 53 ] RRMM (≥ 2 prior LOTs) IRd 54 13 – – – 38.5 7.7 9.6 21.2 Beksac et al. [ 56 ] RRMM Revlimid ® 74 2L: 22.7 3L: 20.1 – Mean: 122.3 – 54.1 22.5 55 22.5 Generic lenalidomide 110 2L: 30.3 3L: 38.1 – Mean: 123.3 – 60 28.8 50 21.2 Pektas et al. [ 36 ] RRMM 2L/3L therapy 107 – 2L: 10.4 3L: 12.8 – – – – – Tekinalp et al. [ 40 ] RRMM Daratumumab 134 8 – 11.6 55.9 – ≥ VGPR: 35.8 – Bolaman et al. [ 57 ] RRMM Revlimid ® 55 – – – – 67.7 14.5 45.4 7.2 Generic lenalidomide 43 60.4 20.9 18.6 20.9 Althomali et al. [ 28 ] RRMM Daratumumab 32 12 1-year: 50.2 – 1-year: 63 59.4 – ≥ VGPR: 40.7 18.8 Beksac et al. [ 54 ] RRMM (≥ 3 prior LOTs) Daratumumab monotherapy 42 5.5 18-month: 31.0 NR 18-month: 59.5 45.2 2.4 9.5 33.3 Cengiz et al. [ 72 ] RRMM Salvage ASCT 22 – 1-year: 43.2 – 2-year: 55.8 – 18.2 54.5 22.7 Selinexor 10 – 1-year: 37.3 – 2-year: 54.9 – 0 20 40 Beksac et al. [ 71 ] RRMM Elotuzumab plus pomalidomide or lenalidomide or bortezomib and dexamethasone 50 5.5 Of pts with > 3 LOTs Len: 2.9 Pom: 6.5 – Of pts with > 3 LOTs Len: 11.7 Pom: 17 – Len: 54.9 Pom: 61.4 – – – Bolaman et al. [ 58 ] RRMM Revlimid ® 55 – – – – 60 14.5 45.4 7.2 Generic lenalidomide 43 – – – – 39.5 20.9 18.6 20.9 Soyer et al. [ 38 ] RRMM Rd 120 21 – 32 – 72.5 19.2 Beksac et al. [ 55 ] RRMM Daratumumab 39 5.5 1-year: 56.9 35.9 5.1 2.6 11 Ozsan et al. [ 59 ] RRMM (heavily pretreated) Pomalidomide 117 5.6 – 8.4 – 35 – VGPR + CR: 11 24 Saydam et al. [ 60 ] RRMM Rd 120 21 – 32 – 72.5 19.2 – – Sevindik et al. [ 61 ] RRMM (heavily pretreated) Carfilzomib 152 6 – 10.4 – 40.8 – VGPR + CR: 13.2 27.6 Yalnız et al. [ 41 ] RRMM 19 59 days – 120 days – – – – – Ozkan et al. [ 73 ] RRMM Thalidomide 34 – 1-year: 64.7 5-year: 5.9 60.5 1-year: 85.3 5-year: 14.7 – – – – Lenalidomide 34 – 1-year: 76.4 44 1-year: 100 – – – – MM Yılmaz et al. [ 42 ] MM Melphalan 200 mg/m 2 with ASCT 130 33.1 – 125.3 – – – – – Melphalan 140 mg/m 2 with ASCT 26 42.4 – 62.9 – – – – – Bostankolu et al. [ 117 ] MM Melphalan with ASCT 256 – – – – – 64.9 5.2 15.9 Melphalan 200 mg/m 2 163 – – – – – 72.1 5.6 14.9 Melphalan 140 mg/m 2 93 – – – – – 52.2 4.5 17.8 Elsergany et al. [ 119 ] MM ASCT – – – – – – ≥ VGPR: 84 15.4 Ipek et al. [ 120 ] MM VCd induction 72 – – 49.4 – – 12.5 48.6 26.4 Kassem et al. [ 33 ] MM VCd 15 DFS: 20 – 37.5 – – – – – VRd 2 DFS: 15 – 25.8 – – – – – VTd 2 DFS: 61.5 – 69.4 – – – – – Endoxan-dexamethasone 4 DFS: 0 – 4.1 – – – – – Sulu et al. [ 39 ] MM Patients who received uHD 70 – – 30 1-year: 39 – – – – Patients who did not receive uHD 70 – – 84 – – – – Serin et al. [ 130 ] MM – 244 42.3 5-year: 42 10-year: 21 – 5-year: 76 10-year: 53 – – – – Malkan et al. [ 125 ] MM Single ASCT 211 Mean: 2344 days – Mean: 4011 days – – – ≥ VGPR: 49.8 20.9 Double ASCT 17 Mean: 685 days – Mean: 3526 days – – – ≥ VGPR: 29.4 23.5 Şahin et al. [ 70 ] MM – 310 14 – 41 – – – – – Çiftçiler et al. [ 31 ] MM ASCT 180 – 5-year DFS: 54 – 5-year: 80 – – ≥ VGPR Pre-ASCT: 16.3 Post-ASCT: 92.9 – Kassem et al. [ 121 ] MM VCd – – 20.3 – – – – – VRd – – – 26.4 – – – – – VTd – – 44.5 Endoxan-dexamethasone – – 5.1 Kirik et al. [ 69 ] MM Overall 200 43.8 – – 5-year: 71 – – – – VCd induction followed by ASCT 156 55.3 – – 5-year: 79 – – – – Umıt et al. [ 75 ] MM Age ≥ 65 years 80 – – 17 – – – – – Beksac et al. [ 62 ] MM Lenalidomide 102 – – – – 90.2 26 52 22 Revlimid ® 49 – – – – 73.5 – – – Generic lenalidomide 53 – – – – 67.9 – – – Gmati et al. [ 131 ] MM ASCT 60 – 1-year: 84.5 5-year: 43.1 – 1-year: 94.3 5-year: 70.5 – 31 sCR: 47 20 0 Alam et al. [ 26 ] MM – 32 – – – – – – ≥ VGPR: 72 – Onec et al. [ 126 ] MM – 66 – – 39.0 – – – – – 2L second line, 3L third line, allo-SCT allogeneic stem cell transplant, ASCT autologous stem cell transplant, BPd bendamustine + pomalidomide + dexamethasone, CR complete response, DCO data cutoff, DFS disease-free survival, FISH fluorescence in situ hybridization, HRCA high-risk cytogenetic abnormality, IRd ixazomib + lenalidomide + dexamethasone, Len lenalidomide, LOT line of therapy, mDFS mean disease-free survival, MM multiple myeloma, mOS median overall survival, mPFS median progression-free survival, NDMM newly diagnosed multiple myeloma, NR not reached, ORR overall response rate, OS overall survival, PFS progression-free survival, Pom , pomalidomide, PR partial response, Rd lenalidomide + dexamethasone, RRMM relapsed refractory multiple myeloma, sCR stringent complete response, SCT stem cell transplant, uHD urgent hemodialysis, VAD vincristine + adriamycin + dexamethasone, VCd bortezomib + cyclophosphamide + dexamethasone, Vd bortezomib + dexamethasone, VGPR very good partial response, VRd bortezomib + lenalidomide + dexamethasone, VTd bortezomib + thalidomide + dexamethasone

Response Rates

The overall response rate (ORR) in patients with NDMM was reported in three articles ( N = 279) as 60.3% (complete response [CR] not reported) [ 34 ] and 80.0% (including CR in 21.1%) [ 50 ] in two studies from Turkey and as 83% (≥ CR in 37%) in a study from Saudi Arabia [ 51 ].

ORR was reported in 13 studies of patients with RRMM ( N = 1201), ranging from 35% to 72.5%, with CR rates of 2.4–28.8% [ 28 , 38 , 40 , 52 – 61 ]. The REPAIR study reported decreasing ORRs and ≥ CR rates with increasing LOTs, with ORRs of 79.0%, 62.2%, 45.7% and 12.4% and ≥ CR rates of 47.9%, 39.1%, 17.8% and 6.2% at 1L, 2L, 3L, and fourth line, respectively [ 27 ].

Four studies reported on response rates in patients with RRMM who were treated with daratumumab, with ORRs of 35.9–59.4%, including CR rates of 2.4–28.8% [ 28 , 40 , 54 , 55 ]. This included one study that focused on 42 heavily pretreated patients (three or more prior LOTs, including a PI and an IMiD) from 25 centers across Turkey, in which an objective response was reported in 45.2% of patients, including a CR in 2.4% [ 54 ].

Six studies reported response rates in patients with RRMM treated with lenalidomide, which ranged from 38.5% to 72.5% with CR rates of 7.7–28.8% [ 38 , 53 , 56 – 58 , 60 ]. Notably, ORRs with lenalidomide decreased with its initiation in later lines of therapy: 62.9%, 16.1% and 6.5% at 2L, 3L and fourth line and beyond, respectively [ 56 ].

Four articles reported comparisons of response rates between brand-name lenalidomide (Revlimid ® ) and generic versions in patients, with most reporting only slight differences in ORRs between the two versions [ 56 – 58 , 62 ]. One single-center study in Turkey compared the use of brand-name bortezomib (Velcade ® ) and a generic version, in combination with cyclophosphamide and dexamethasone, in patients with NDMM; response rates were similar between the two versions [ 50 ].

PFS

Median PFS was reported in 24 articles, ranging from 2 to 97.7 months (Table 2 ). Eight of these were conducted in patients with NDMM ( N = 1191), in which median PFS ranged from 14 to 97.7 months [ 63 – 70 ]. This included six studies reporting data on patients who received ASCT ( N = 592), in which the median PFS ranged from 20 to 97.7 months [ 64 – 69 ]. One single-center study in Turkey compared clinical outcomes in patients with NDMM aged ≤ 65 vs > 65 years, and reported significantly longer median PFS in patients aged ≤ 65 years than in those aged > 65 years (44 vs 30 months; p = 0.02) [ 68 ].

Another single-center study in Turkey compared the efficacy of induction with bortezomib + dexamethasone (Vd) versus VCd in patients with NDMM and reported a median PFS of 67.1 and 97.7 months, respectively, with 5-year PFS rates of 56% and 59%, respectively [ 65 ].

Median PFS was reported in 12 studies of patients with RRMM, which ranged from 2 to 38.1 months [ 28 , 38 , 40 , 41 , 53 – 56 , 59 – 61 , 71 ]; four studies reported 1-year PFS rates of 35.7–76.4% [ 28 , 54 , 72 , 73 ]. Median PFS tended to be shorter in patients with a greater number of prior LOTs. In a multicenter retrospective study of patients in Turkey with more than two prior LOTs, those who received elotuzumab and lenalidomide or pomalidomide had a median PFS of 7.5 and 6.5 months, respectively [ 71 ]. This compared with 2.9 and 6.5 months in patients with more than three prior LOTs; however, these differences were not statistically significant [ 71 ]. Patients in a tertiary care hematology clinic in Turkey initiating lenalidomide at 2L had a median PFS of 29.2 months compared with 26.4 months at 3L [ 56 ].

One single-center study in Egypt ( N = 25) compared clinical outcomes in patients with MM with and without high-risk cytogenetic abnormalities (HRCA) and found that patients with t(4;14) had a statistically significantly shorter median time to progression than those without t(4;14) (36.0 versus 88.5 months; p = 0.001). Similarly, patients with del(17p) had a significantly shorter median PFS than those without (23.3 versus 52.94 months; p = 0.014) [ 66 ]. No significant differences were observed between patients with and without t(11;14) (49.1 versus 41.1 months; p = 0.39) and del(13q) (20.7 versus 51.0 months; p = 0.282) [ 66 ]. A second single-center Egyptian study compared VAD with Vd induction, followed by ASCT and thalidomide maintenance, in patients with and without t(4;14) and/or del(17p). In patients without these cytogenetic abnormalities, median PFS was significantly longer with Vd than VAD induction (31 versus 26 months; p = 0.018); similarly, median PFS was significantly longer with Vd than VAD induction in patients with t(4;14) and/or del(17p) (not reached [NR] versus 20 months; p = 0.016) [ 67 ]. With a median follow-up of 17.5 months, for patients treated with VAD and Vd, respectively, the PFS rate was 77.8% and 85.2% in those without t(4;14) or del(17p), and 23.1% and 69.2% in those with t(4;14) and/or del(17p) [ 67 ].

Time to Progression

The REPAIR study reported decreasing median time to progression (TTP) with increasing LOTs: 23.9, 10.1, and 5.9 months following the initiation of first, second, and third LOTs, respectively [ 27 ]. Among patients with lenalidomide-refractory disease, median TTPs were 16.7, 8.9, and 8.0 months, respectively. In lenalidomide-sensitive disease, median TTPs were 27.3, 38.8, and 10.0 months following the first, second, and third LOTs, respectively [ 27 ]. In a Turkish study of patients with RRMM initiating 2L and 3L therapy (approximately half and two-thirds of whom were treated with a lenalidomide-containing regimen), 57.9% and 25.6% experienced disease progression, respectively, although the follow-up duration was not specified [ 36 ].

OS

Median OS was reported in 27 articles, ranging from 4 to 125.3 months (Table 2 ); eight of these reported on patients with NDMM and had a median OS ranging from 22 to 122.2 months [ 29 , 51 , 65 – 68 , 70 , 74 ]; 12 articles reported on patients with RRMM, in which median OS ranged from 4 to 60.5 months, with one study reporting a mean OS of 122.3–123.5 months [ 36 , 38 , 40 , 41 , 52 , 54 , 56 , 59 – 61 , 71 , 73 , 75 ]. Factors associated with longer median OS reported in two studies included younger age, female sex, and receiving ASCT [ 23 , 68 ].

In a single-center Turkish study comparing Vd and VCd as induction therapy in patients with NDMM, median OS values were 113.1 and 122.2 months ( p = 0.47), respectively, with 5-year OS rates of 75% and 83%, respectively [ 65 ]. Notably, mortality rate was significantly greater with Vd than VCd (19.4% versus 4.5%; p = 0.01) [ 65 ]. In a separate single-center Turkish study comparing thalidomide ( N = 34) and lenalidomide ( N = 34) as a second, third, or fourth LOT, median OS values were 65.5 and 44 months with thalidomide and lenalidomide, and 1-year mortality rates were 17.6% and 0%, respectively [ 73 ]. In patients with more than three prior LOTs, median OS was not significantly different between those treated with elotuzumab + lenalidomide and those treated with elotuzumab + pomalidomide (11.7 and 17 months, respectively) [ 71 ].

A single-center study in Egypt reported that in patients without HRCA, median OS was not reached in those treated with either VAD or Vd induction, and OS rates of 92.6% and 96.3%, respectively, were reported after a median follow-up of 17.5 months [ 67 ]. In patients with del(17p) and/or t(4;14) mutations, median OS was 22 months with VAD and not reached with Vd, with OS rates at data cut-off of 53.8% and 69.2%, respectively [ 67 ]. In a separate Egyptian study, patients with t(4;14) had a significantly shorter median OS than those without t(4;14) (36.6 versus 85.0 months; p = 0.005), and patients with del(17p) also had a significantly shorter median OS than those without (35.5 versus 81.0 months; p = 0.008) [ 66 ]. No significant differences were seen between patients with and without t(11;14) (93.0 versus 48.1; p = 0.038) and del(13q) (35.0 versus 77.8; p = 0.208) [ 66 ]. The presence of more HRCAs was associated with decreasing OS: median OS in patients with zero, one or two HRCAs were 57, 32 and 6 months, respectively [ 29 ].

QOL

QOL was reported in four articles [ 37 , 76 – 78 ]. In 92 Turkish patients with MM who participated in an online survey, the mean (SD) numeric rating scale (a measure for pain where 0 indicates “no pain” and 10 indicates “the worst pain imaginable” over the past week) was 3.9 (2.6). The mean (SD) Short Form-12 (SF-12) health-related QOL (HRQOL) mental and total physical component scores, respectively, were 45.5 (24.8) and 39.1 (25.4); higher scores indicate greater QOL [ 76 ]. The study also utilized the Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being Scale-12 (FACIT-Sp-12, version 4), with a mean (SD) score of 28.1 (9.8) out of a maximum of 48; higher scores represent greater spiritual well-being. In the Meaning, Peace, and Faith subscales, mean (SD) scores were 10.3 (3.5), 8.8 (3.4) and 8.9 (4.6), respectively [ 76 ]. Notably, there was a negative correlation between pain scores in the previous week and FACIT-Sp-12 total and subscale scores and in SF-12 physical and mental component scores [ 76 ]. The SF-12 physical and mental component scores, respectively, were associated with total FACIT-Sp-12 scores ( r = 0.304 and r = 0.416), with Meaning ( r = 0.345, r = 0.465) and Peace ( r = 0.481 and r = 0.579) subscales, and with pain scores in the previous week ( r = −0.499 and r = −0.349) [ 76 ].

Half of the 62 patients with MM and chemotherapy-induced peripheral neuropathy from a single center in Saudi Arabia reported “quite a bit” or “very much” bone aches or pain (50.0%), and pain in the back, hip, arm/shoulder, and chest were reported in 42.6%, 37.7%, 32.8%, and 14.8%, respectively [ 37 ]. Notably, 49.1% of patients responded “quite a bit” or “very much” when asked if their pain increased with activity [ 37 ].

In a single-center study of 42 patients with fractures due to spinal infiltration in Turkey, statistically significant differences were found between pre- and postoperative visual analog scale (VAS) and Oswestry Disability Index scores, respectively, in patients who underwent kyphoplasty ( p = 0.0001 and p = 0.002), vertebroplasty ( p = 0.0001 and p = 0.0001) and both vertebroplasty and kyphoplasty ( p = 0.0002) [ 77 ].

In a separate single-center Turkish study of 49 patients with MM and bone lesions, all patients reported moderate to severe pain; the mean (range) duration was 4 (1–9) months [ 78 ]. Of the 57 lesions in these patients, 48 were associated with actual or impending pathologic fractures leading to limited motion. Surgical procedures were performed on all 57 lesions, and all patients experienced improvements in pain, extremity motion, and mobility after surgery [ 78 ]. Mean (SD) VAS scores decreased from 8.75 (1.2) before surgery to 3.21 (1.56) at discharge after a mean of 6.7 (3.4) days ( p = 0.0001) [ 78 ]. Similarly, mean (SD) Musculoskeletal Tumor Society functional scores improved from 9.1% (6.4%) before surgery to 76% (14.9%) at the last follow-up ( p = 0.0001) [ 78 ].

Safety and Tolerability of Treatments Received

Adverse events (AEs) were reported in 27 articles. Hematologic AEs—such as anemia, thrombocytopenia, and neutropenia—were commonly reported; common nonhematologic AEs included peripheral neuropathy, diarrhea, and infection (including pneumonia) (Table 3 ). Table 3 Adverse events reported in patients treated for MM Study Patient population Intervention/subpopulation N Overall AEs Hematologic AEs Nonhematologic AEs Proteasome inhibitor Kul et al. [ 81 ] NDMM, normal cytogenetics VCd 68 – – Bortezomib-induced peripheral neuropathy: 50% NDMM, abnormal cytogenetics VCd 45 – – Bortezomib-induced peripheral neuropathy: 17.8% Mersin et al. [ 50 ] NDMM VCd (Velcade ® ) 42 47.6% Anemia: 9.5% Neutropenia: 4.8% Thrombocytopenia: 7.1% Neuropathy: 21.4% URTI: 9.5% Diarrhea: 9.5% VCd (generic bortezomib) 53 41.5% Anemia: 15.1% Neutropenia: 4.8% Thrombocytopenia: 7.5% Neuropathy: 11.3% URTI: 7.5% Diarrhea: 5.7% Ciftciler et al. [ 65 ] NDMM Vd 36 – Neutropenia: 5.6% Neutropenic fever/infection: 2.7% – VCd 67 – Neutropenia: 32.8% ( p = 0.002) Neutropenic fever/infection: 2.9% – Sevindik et al. [ 61 ] RRMM Carfilzomib 152 – Any: 61.8% Cardiovascular AEs: 26.3% Renal AEs: 9.2% Ateşaʇaʇlu et al. [ 79 ] MM Bortezomib (SC) 74 – – Dose reduction due to neurotoxicity: 19% Bortezomib (IV) 55 – – Dose reduction due to neurotoxicity: 31% IMiD Açar et al. [ 52 ] RRMM BPd 11 – Neutropenia: 36.4% Anemia: 18.2% Beksac et al. [ 56 ] RRMM Revlimid ® 74 – – Fatigue: 51.4% Diarrhea: 36.5% Muscle weakness: 33.8% Rash: 35.1% Peripheral neuropathy: 18.9% VTE: 2.7% Pneumonitis: 32.4% Treatment discontinuation due to AE: 31.1% Generic lenalidomide 110 – – Fatigue: 52.8% Diarrhea: 37.2% Muscle weakness: 32.7% Rash: 39.1% Peripheral neuropathy: 20.9% VTE: 6.4% Pneumonitis: 30.0% Treatment discontinuation due to AE: 29.1% Bolaman et al. [ 57 ] RRMM Revlimid ® 55 – Neutropenia: 61.8% Thrombocytopenia: 38.2% Anemia: 67.3% Febrile neutropenia: 40.0% – Generic lenalidomide 120 – Neutropenia: 48.8% Thrombocytopenia: 34.9% Anemia: 76.7% Febrile neutropenia: 51.2% – Beksac et al. [ 62 ] MM Revlimid ® 49 – Grade ≥ 3: 37.7% Fatigue: 58.3% Muscle weakness: 47.4% Diarrhea: 39.6% Rash: 37.7% Peripheral neuropathy: 27% Pneumonia: 22.6% Generic lenalidomide 53 – Grade ≥ 3: 36.7% Fatigue: 51.3% Muscle weakness: 33.3% Diarrhea: 24.9% Rash: 30.6% Peripheral neuropathy: 19.4% Pneumonia: 42.9% Bolaman et al. [ 58 ] RRMM Revlimid ® 55 – Nausea: 23.6% Vomiting: 18.2% Fatigue: 56.4% Pyrexia: 20.0% URTI: 30.9% Pneumonia: 21.8% Back pain: 23.6% Muscle cramp: 23.6% Muscle weakness: 40.0% Skin dry: 7.3% Skin erythema: 1.8% – Generic lenalidomide 43 – Nausea: 48.8% Vomiting: 39.5% Fatigue: 41.9% Pyrexia: 46.5% URTI: 65.1% Pneumonia: 55.8% Back pain: 55.8% Muscle cramp: 51.2% Muscle weakness: 58.1% Skin dry: 27.9% Skin erythema: 16.3% – Soyer et al. [ 38 ] RRMM Rd – Anemia: 12.5% Thrombocytopenia: 9.2% Neutropenia: 28.3% Pancytopenia: 2.5% Pneumonia: 15.8% Fatigue: 14.2% Neuropathy: 2.5% Cutaneous reaction: 1.7% Diarrhea: 2.5% Renal failure: 1.7% Ozsan et al. [ 59 ] RRMM Pomalidomide 117 – Any: 77% Fatigue: 27.3% Pneumonia: 20.5% Sepsis: 12% Renal: 6% Saydam et al. [ 60 ] RRMM Rd 120 – Anemia: 12.5% Thrombocytopenia: 9.2% Incidence rate of second primary malignancies: 0.93 per 100 PY Pneumonia: 15.8% Fatigue: 14.2% Herpes infection: 0.8% Firatli Tuglular et al. [ 133 ] RRMM Rd 111 Grade 3/4: 36.9% Grade 3/4 Neutropenia: 8.1% Pneumonia: 5.4% Anemia: 3.6% Thrombocytopenia: 1.8% Any grade VTE: 1 (0.9%) Ozkan et al. [ 73 ] RRMM Thalidomide 34 – Cytopenia: 26.5% Thrombosis: 2.9% Neuropathy: 38.2% Pneumonia: 5.8% Constipation: 47.1% Rash: 8.8% Lenalidomide 34 – Cytopenia: 23.5% Thrombosis: 0 Neuropathy: 0 Pneumonia: 11.8% Constipation: 0 Rash: 0 Anti-CD38 mAb Bakırtaş et al. [ 53 ] RRMM (≥ 2 prior LOTs) IRd 54 40.4% had ≥ 1 AE; 19.1% had Grade ≥ 3 AE Thrombocytopenia: 29.8% Anemia: 31.9% Neutropenia: 27.7% Infective: 19.1% Constipation: 4.3% Diarrhea: 10.6% Skin rash: 10.6% Hypertension: 8.5% Hepatotoxicity: 6.4% Tekinalp et al. [ 40 ] RRMM Daratumumab 134 – Any grade/grade 3–4 , n Neutropenia: 48/28 Thrombocytopenia: 36 /19 Anemia: 55/17 Any grade/grade3–4, n Neuropathy: 8/1 Diarrhea: 11/1 Vomiting: 14/0 Pneumonia: 32/9 IRR: 18/1 Althomali et al. [ 28 ] RRMM Daratumumab 32 – Most common grade 3/4 AEs: Anemia: 46.9% Thrombocytopenia: 43.8% Neutropenia: 37.5% IRR: 46.9% (G3: 9.4%) Beksac et al. [ 54 ] RRMM (≥ 3 prior LOTs) Daratumumab monotherapy 42 76 AEs reported Grade ≥ 3: 43.4% Events Thrombocytopenia: 13 Anemia: 12 Neutropenia: 8 Events Neuropathy: 3 Fatigue: 11 URTI: 3 Lower respiratory tract infection: 8 Other infection: 8 IRR: 10 Beksac et al. [ 55 ] RRMM Daratumumab 39 – Thrombocytopenia: 28.2% Fatigue: 25.6% Anemia: 25.6% Melphalan Amikishiyev et al. [ 132 ] MM ASCT with high-dose melphalan conditioning and antimicrobial prophylaxis – Median duration of neutropenia: 8 days Fever requiring antimicrobial treatment: 90.6% Fever of unknown origin: 53% Primary bacteremia: 12.6% Pneumonia: 12.6% Severe skin infection: 5.3% Candidial and/or herpetic stomatitis: 10.6% Invasive fungal infection: 8% No infection-related death during study period Aypar et al. [ 80 ] MM High-dose melphalan 114 – – Most frequently reported grade 3/4: Infection: 64.9% Diarrhea: 25.4% Mucositis: 9.6% Pulmonary toxicity: 9.6% Grade 1/2: Mucositis: 33.3% Diarrhea: 53.5% ICU: 2.6% TRM: 1.75% Bortezomib + high-dose melphalan 53 – – Most frequently reported grade ¾: Infection: 54.7% Diarrhea: 37.7% Mucositis: 13.2% Pulmonary toxicity: 18.9% Grade ½: Mucositis: 60.4% Diarrhea: 56.6% ICU: 7.5% TRM: 3.7% Other/not specified Gursoy et al. [ 32 ] NDMM – 455 – – 6-month VTE: 7% Farghaly et al. [ 85 ] MM – – – Anemia: 54% Bone pain: 51% Microbial infections: 39% Cengiz et al. [ 72 ] MM Salvage ASCT 22 Prolonged isolated thrombocytopenia: 13.6% Infection: 9.1% Selinexor 10 – Thrombocytopenia: 20% Fatigue: 30% Nausea: 50% Neuropathy: 10% Kassem et al. [ 121 ] MM – 81 – – Hepatic AEs ALT increase: 1.6% AST increase: 13.6% Bilirubin increase: 15.0% Umit et al. [ 75 ] RRMM, aged ≥ 60 years – 80 – – Fall risk: 27.5% Autonomous neuropathy: 36.3% Yalnız et al. [ 41 ] RRMM – 19 – Grade 3–4 TRAE: Anemia: 9% Neutropenia: 55% Thrombocytopenia: 23% Grade 3-4 TRAE: Infection: 9% Nausea: 4% AE adverse event, ALT alanine aminotransferase, ASCT autologous stem cell transplant, AST aspartate aminotransferase, BPd bendamustine + pomalidomide + dexamethasone, ICU intensive care unit, IMiD immunomodulatory imide, IRd isatuximab + lenalidomide + dexamethasone, IRR infusion-related reaction, IV intravenous, LOT line of therapy, mAb monoclonal antibody, MM multiple myeloma, NDMM newly diagnosed multiple myeloma, Rd lenalidomide + dexamethasone, RRMM relapsed and/or refractory multiple myeloma, SC subcutaneous, TRAE treatment-related adverse event, TRM treatment-related mortality, URTI upper respiratory tract infection, VCd bortezomib + cyclophosphamide + dexamethasone, Vd bortezomib + dexamethasone, VTE venous thromboembolism

Anemia, thrombocytopenia, and neutropenia were frequently reported in studies focusing on daratumumab, with one study of 32 patients with RRMM in Saudi Arabia reporting grade 3/4 events in 46.9%, 43.8%, and 37.5% of patients, respectively [ 28 ]; in a second study in 134 patients with RRMM in Turkey, these respective results were 30.9%, 52.8% and 66.2% [ 40 ]. Infusion-related reactions were also commonly reported with daratumumab, occurring in 46.9% of patients in one study and in 13.4% of patients in a second study [ 28 , 40 ]. Notably, the specific AEs counting towards infusion-related reactions were not detailed in either study.

One Turkish study of 152 patients with RRMM treated with carfilzomib reported hematologic AEs in 61.8% of patients and cardiovascular AEs in 26.3%, including heart failure, pulmonary hypertension and systemic hypertension [ 61 ]. Cardiac AEs were also reported in 10.6% of patients with RRMM in Turkey treated with ixazomib + lenalidomide + dexamethasone (IxaRd; N = 54) [ 53 ].

In studies focusing on bortezomib-containing regimens, peripheral neuropathy was reported in 11.3–50% of patients [ 50 , 79 – 81 ], with one study reporting dose reductions due to neurotoxicity in 31% of patients treated with intravenous bortezomib [ 79 ]. One study compared Velcade ® and generic bortezomib and found similar overall AE rates (47.6% versus 41.5%, p = 0.55) [ 50 ]. While numerically more patients experienced neuropathy with the original drug than the generic version (21.4% versus 11.3%; p = 0.18), fewer patients experienced anemia with the original drug (9.5% versus 15.1%; p = 0.41); the differences were not statistically significant [ 50 ].

Three of the four studies comparing Revlimid ® and generic lenalidomide reported no significant differences in the rates of any-grade AEs between the two drugs [ 56 , 58 , 62 ]; however, one study reported a significantly lower rate of pneumonia with Revlimid ® (22.6% versus 42.9%; p = 0.035) [ 62 ], and another reported significantly higher rates of grade ≥ 3 hematologic toxicity with Revlimid ® (25.7% versus 13.6%; p = 0.021), although this difference disappeared when adjusted for LOT [ 56 ]. A separate study reported significantly higher rates of several AEs (nausea, vomiting, fatigue, edema, URTI, pneumonia, back pain, pyrexia, muscle cramps, muscle weakness, skin dry, and skin erythema), with generic lenalidomide than with Revlimid ® but a significantly higher incidence of grade 3/4 pyrexia with Revlimid ® than with generic lenalidomide (3.6% versus 0%; p = 0.04) [ 57 ].

One study compared the use of brand-name versus generic melphalan for conditioning prior to ASCT and found similar rates of diarrhea, oral mucositis and fever and similar engraftment kinetics between the treatments [ 82 ].

HCRU

Five studies reported on HCRU in the Gulf region, Egypt, Saudi Arabia, and the UAE (Table 4 ) [ 83 – 87 ]. In a study examining the financial burden of MM in the Gulf region (Saudi Arabia, Kuwait, the UAE, Qatar, and Oman), the weighted average annual direct cost per patient was US $125,000–372,000; patients with RRMM incurred greater individual costs than those with NDMM [ 85 ]. In a separate study of patients with NDMM treated in the UAE, annual drug, nondrug medical, and total costs for the first year of treatment were US $7,825,390.33–8,475,601.36, $3,674,228.45–8,954,474.06, and $12,149,829.82–16,779,864.40, respectively; in the fifth year, these costs were US $1,198,759.70–2,079,734.79, $451,416.47–1,924,099.39, and $1,650,176.17–4,003,834.17 [ 86 ]. Notably, this study found that changing from intravenous daratumumab to subcutaneous administration resulted in substantial savings in costs associated with premedication, managing AEs, administration, medical staff, and other indirect costs [ 86 ]. Table 4 Median/mean healthcare costs per patient (US $, as of 17 November 2025) Study Geography Intervention All-cause costs Cancer-related treatment costs Cost-effectiveness Farghaly et al. [ 85 ] MENA – 125–372,000 – – Elsisi et al. [ 83 ] Egypt DVd versus Kd – – DVd resulted in an increase of 0.34 QALY and 0.43 LY over Kd Elsisi et al. [ 84 ] Egypt – – – Cost savings with initiation of lenalidomide in NDMM Year 1: 18,457 Year 2: 37,783 Year 3: 45,420 Cost savings with initiation of lenalidomide in RRMM Year 1: 23,436 Year 2: 71,392 Year 3: 126,302 Maroun et al. [ 87 ] Saudi Arabia KRd – Per cycle: 7300 Per ORR: 345,591 – DRd – Per cycle: 11,947 Per ORR: 896,542 – EloRd – Per cycle: 10,474 Per ORR: 403,359 – IxaRd – Per cycle: 9792 Per ORR: 403,840 – Hamad et al. [ 86 ] UAE – Year 1: 12,149,830–16,779,864 Year 5: 1,650,176–4,003,834 Year 1: 7,825,390–8,475,601 Year 5: 1,198,760–2,079,735 – DRd daratumumab + lenalidomide + dexamethasone, DVd daratumumab + bortezomib + dexamethasone, EloRd elotuzumab + lenalidomide + dexamethasone, IxaRd ixazomib + lenalidomide + dexamethasone, Kd carfilzomib + dexamethasone, KRd carfilzomib + lenalidomide + dexamethasone, LY life-year, MENA Middle East and North Africa, NDMM newly diagnosed multiple myeloma, ORR overall response rate, QALY quality-adjusted life year, RRMM relapsed/refractory multiple myeloma, UAE United Arab Emirates

A study in Saudi Arabia compared costs associated with daratumumab + lenalidomide + dexamethasone (DRd), carfilzomib + lenalidomide + dexamethasone (KRd), elotuzumab + lenalidomide + dexamethasone (EloRd), and ixazomib + lenalidomide + dexamethasone; KRd had the lowest average cost per treatment cycle (US $7299.73), while DRd had the greatest average cost per treatment cycle (US $11,947.20). The cost per ORR was also lowest with KRd (US $345,591.20) and highest with DRd (US $896,541.87) [ 87 ].

A study in Egypt modeling a hypothetical health plan estimated that introducing lenalidomide in patients with NDMM and RRMM, respectively, would introduce a cost savings of US $18,457.03 and $23,436.44 in year 1; US $37,783.32 and $71,391.85 in year 2; and US $45,419.91 and $126,301.68 in year 3 [ 84 ]. A separate study in Egypt estimated that, over a 20-year time horizon, when compared with Kd, DVd resulted in an increase of 0.43 life-years and 0.34 quality-adjusted life years [ 83 ].

Discussion

Epidemiology and Disease Burden

Compared with global rates, the ASIR of MM in MENA is marginally lower: 1.49 per 100,000 individuals compared with a global rate of 1.92 per 100,000 individuals [ 7 ]. However, it is unclear whether this reported ASIR accurately reflects the incidence of MM in MENA, or if it is underestimated owing to potential gaps in diagnosis and reporting in the region. In the MENA region, the incidence of MM was higher in men and older individuals (aged > 50 years) than in women or younger individuals—in alignment with global trends [ 3 ]. Only two independent studies reported on incidence in Turkey and Saudi Arabia, highlighting a significant data gap in the region [ 7 , 19 – 23 ]. Few studies reported on the incidence and prevalence of MM in the MENA region, with data largely sourced from the IARC’s GLOBOCAN database. This lack of comprehensive data may hinder effective public health planning and resource allocation for MM in the MENA region.

Similar to global trends, the incidence of MM in MENA has been increasing over time. Notably, the rate of increase appears higher in the MENA region than globally, with an increase of 14.95% in ASIR between 1990 and 2019 in MENA compared with a global rate of 10.99% [ 7 ], and an increase in incident cases from 1990 to 2016 of 192% and 126%, respectively [ 19 ]. In particular, men in Turkey were reported to have the greatest, statistically significant increases in incidence globally between 2001 and 2019 (AAPC 5.63, 95% CI 1.12–10.35; p = 0.020), increasing across all ages; women in Turkey did not experience a significant increase [ 21 ]. In Turkey, ASIRs for total cancers and for cancers of various sites increased between 2006 and 2020, and is projected to continue increasing substantially in the future across the MENA region [ 88 , 89 ]. It remains to be seen whether this represents true changes in cancer incidence or if this is a reflection of progressive improvements in access to healthcare services and enhanced diagnostic capacity leading to increased detection. Although other countries reported higher AAPCs, such as Iceland (AAPC 7.94) and Kuwait (AAPC 7.06), the differences were not considered statistically significant [ 21 ]. Notably, the median age of patients with MM identified in the current literature review ranged from 43 to 70 years, which is lower than the global median of 70 years [ 7 ]. This wide range of median ages likely reflects the variation in populations and study designs in studies conducted across the region.

In the MENA region, a significant proportion of patients had advanced disease at diagnosis or study entry; 41.4% had stage III disease. Limited awareness of MM symptoms from healthcare provider and patient perspectives can also lead to delayed diagnosis; for example, pain symptoms of MM can be dismissed as musculoskeletal in nature, particularly in community hospitals [ 22 ]. Additionally, patients may be reluctant to seek medical attention even when experiencing symptoms, resulting in MM being diagnosed at more advanced stages [ 22 ]. Furthermore, availability and access to imaging such as positron emission tomography/computed tomography and magnetic resonance imaging is limited in some parts of the region, representing further barriers to the diagnostic pathway [ 22 ]. This is in contrast with studies conducted in Spain and the USA, in which 27.0% and 19.0% of patients had stage III disease at enrollment [ 90 , 91 ], but aligns with a study of patients in Asia and Latin America in which 40.8% of patients had stage III disease at enrollment [ 92 ]. Notably, within MENA there is significant variation across the individual countries: while stage III disease was most common at diagnosis or study entry in Saudi Arabia and Turkey, stage I and II disease were most common in Egypt and the UAE, respectively. Furthermore, < 50% of the articles identified in this literature search reported ISS stage. This may reflect localized differences in early access to diagnostic and prognostic tools such as flow cytometry and cytogenetic testing.

Similar to other diverse geographic and socioeconomic regions, such as Latin America, the reporting of cytogenetic testing in the studies retrieved was inconsistent [ 93 ]. Only 25 of the studies identified in our literature search reported on cytogenetic risk factors; furthermore, a significant proportion of patients within these studies did not have cytogenetic information available. The presence of certain cytogenetic abnormalities, such as del(17p), is associated with poor clinical outcomes [ 29 , 66 ], and detection of these abnormalities can help guide clinical decision-making [ 48 ]. Together, this lack of cytogenetic testing and ISS assessment suggests that patients with high-risk disease in the MENA region may be missing out on intensive treatment, leading to inferior outcomes.

Treatment Availability

Although treatment options for MM have evolved over the past decade, access to novel treatments varies between countries in the MENA region, impacted by government reimbursement policies and access to private healthcare. Across the MENA region, and in the individual countries of interest, bortezomib was the most frequently used treatment. Treatment patterns differed between LOTs. Daratumumab was more commonly used in patients with RRMM, while the use of lenalidomide was similar between patients with NDMM and RRMM in the MENA region. This could at least in part be explained by regulatory approvals—in Turkey, daratumumab was only approved for use in patients with NDMM in 2024, resulting in few patients treated with these drugs in the articles included in this review [ 94 ]. Few studies reported on treatment patterns in individual countries, and those that did included small sample sizes, with one exception: a Turkish analysis of patients in the Sosyal Güvenlik Kurumu receiving treatment for NDMM between 2011 and 2017, which accounted for the majority of the patients ( N = 10,146) identified in this review [ 23 ]. In this analysis of patients, there was an increasing trend of lenalidomide use over the study period (2011–2017), which mirrors global trends [ 23 , 95 , 96 ] and suggests that a growing number of patients may become refractory to lenalidomide at relapse. Because patients retreated with lenalidomide, particularly those with lenalidomide-refractory disease, tend to have worse clinical outcomes [ 27 , 36 ], there is an unmet clinical need for new treatment modalities in this growing patient population.

In recent years, CAR T-cell therapies and bispecific T-cell engagers have demonstrated efficacy in the treatment of RRMM, and have been approved for use in the USA and other countries [ 97 – 100 ]; in the MENA region, these therapies are approved in Saudi Arabia, Turkey, and the UAE [ 101 ]. However, despite regulatory approvals, access to these novel therapies remains inadequate, primarily owing to a lack of reimbursement and the subsequent financial burden imposed on patients [ 102 ]. Furthermore, these treatments with novel mechanisms of action have unique, potentially life-threatening AEs that require specialized monitoring and management, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, adding strain to resource-limited settings [ 103 ]. In addition, where the infrastructure exists to support these novel therapies, access to these specialized centers is limited to certain urban centers, presenting a barrier to patients living away from these areas [ 22 ].

Nearly all the studies identified in this review were retrospective and observational, suggesting a paucity of clinical trials conducted in the MENA region that presents a hindrance to patients receiving novel treatments. While a number of global clinical trials from the identified articles included study sites in the region, there is a lack of reporting on the MENA patient population. This may have hampered the identification of any potential regional/ethnicity-specific effects of trial medications.

Few localized or regional guidelines exist for the management of MM in MENA, although comprehensive guidelines have recently been published for Saudi Arabia [ 47 , 48 ], Turkey [ 49 ], and the Gulf region [ 43 , 44 ]; guidelines focusing on ASCT, including in the context of MM, have also been published in Turkey [ 45 , 46 ]. Similar to the US Mayo Stratification for Myeloma And Risk-adapted Therapy guidelines [ 104 ] and the recently updated European Hematology Association guidelines [ 105 ], the recent Saudi Myeloma Working Group and Turkish Society of Hematology guidelines recommend an anti-CD38 monoclonal antibody in combination with VRd as 1L treatment for patients with standard-risk NDMM, followed by ASCT in transplant-eligible patients, and bortezomib or lenalidomide maintenance therapy for patients with high-risk disease [ 48 , 49 ]. According to the real-world studies identified in this literature search, while two-thirds of patients received bortezomib, only 15.2% and 4.3% of patients in Saudi Arabia were treated with daratumumab and lenalidomide, respectively. However, it should be noted that the data on treatment patterns in Saudi Arabia are derived from only three studies totaling 211 patients, and may not represent treatment patterns overall [ 25 , 28 , 37 ]. Overall, < 1% of patients were treated with quadruplet therapy, indicating that current treatment patterns are lagging behind guideline recommendations. Given the inherent delay between changes in clinical practice and the publication of real-world data, it remains to be seen whether practice has changed to follow the updated guidelines.

Clinical and Patient Outcomes

The introduction of IMiDs and PIs has significantly improved clinical and patient outcomes in MM over the last two decades. In line with global literature, survival and response rates were variable in the studies identified in this review [ 10 , 106 ]. A recently published meta-analysis of efficacy outcomes in Asia, Africa, LATAM, and Eastern Europe found a consistent and significant association of ASCT use with improved PFS, reporting median PFS ranging from 19 to 46 months in patients who received ASCT [ 107 ]. In our literature review, median PFS ranged from 20 to 97.7 months in this population. Notably, while some publications specified survival outcomes in patients who received ASCT, most did not clearly differentiate outcomes between patients who did or did not receive ASCT and no studies reported direct comparisons. Similar to a literature review of MM in LATAM, ORR and CR rates in our review were generally high, particularly in patients with NDMM (60.3–83% in this review and 50.9–94.4% in LATAM) [ 93 ]. However, outcomes worsened with increasing LOTs, regardless of the treatment used, particularly in patients with lenalidomide-refractory disease. This finding highlights the need for more effective therapies in earlier LOTs to improve patient outcomes.

Few publications reported survival outcomes and response rates together. Notably, a Turkish publication comparing the efficacy of Vd versus VCd in patients with NDMM reported comparable response rates (≥ VGPR: 86.1% versus 88.1%) and median OS (113.1 versus 122.2 months; p = 0.47), but a significantly higher mortality rate with Vd than VCd (19.4% versus 4.5%; p = 0.01) [ 65 ]. While the follow-up duration for each treatment group was not specified, the differences observed across the outcomes raise questions regarding whether comparisons based on single efficacy endpoints adequately reflect true differences in clinical outcomes.

Globally, patients with MM tend to report poor HRQOL as a result of worsening disease symptoms and AEs associated with treatment [ 37 ]. Similarly, studies in MENA identified low QOL scores in patients with MM. In particular, patients frequently reported being in pain [ 37 , 76 ]; all patients with bone lesions reported experiencing moderate to severe pain, and most patients reported limitations in motion that affected functionality [ 78 ]. Surgical procedures provided significant improvements in pain and function, representing an essential part of disease management in patients with MM and bone lesions [ 77 , 78 ]. Notably, the articles identified in our literature search did not report MM-specific QOL scores, such as those from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Myeloma Module or Functional Assessment of Cancer Therapy–Multiple Myeloma, highlighting an area that requires further investigation. A systematic literature review of publications reporting on HRQOL in MM found an association of deeper responses and minimal residual disease negativity with improved HRQOL, while disease progression and increasing LOTs were associated with worse HRQOL [ 108 ]. This reiterates the need for more effective treatments in earlier LOTs to maintain QOL.

While we identified 60 articles reporting efficacy outcomes, only 31 of them reported safety outcomes. Because these were retrospective, observational studies, most of them did not comprehensively capture AEs owing to the reliance on information captured in databases and clinical practice. Overall, few serious AEs were reported, although most patients experienced at least one AE while on treatment. Cytopenia, especially anemia, is common in patients with MM [ 1 ] and can be exacerbated by MM treatments. Anemia, thrombocytopenia, and neutropenia are the most commonly reported hematological AEs. These cytopenias can lead to an increase in the incidence of infections; therefore, prophylactic measures such as prophylactic antibiotics or recombinant granulocyte colony-stimulating factor have been considered for patients with MM [ 109 , 110 ]. Patients experiencing anemia may also require the use of erythropoietin analogs or transfusions [ 109 ].

Of the nonhematological AEs, peripheral neuropathy was frequently reported. Peripheral neuropathy negatively impacts QOL; notably, approximately half of all patients with chemotherapy-induced peripheral neuropathy reported increased pain with activity [ 37 ]. While chemotherapy-induced peripheral neuropathy is generally considered reversible, many patients experience long-lasting neuropathy, highlighting the need for close monitoring and immediate dose adjustment in patients experiencing severe symptoms [ 37 , 111 ]. Additionally, cardiac AEs have been reported in 10.6% of patients treated with IxaRd and in 26.3% of patients treated with carfilzomib [ 53 , 61 ]. Overall, prospective studies are needed to accurately capture the breadth and frequency of AEs impacting patients with MM in the MENA region.

HCRU

RRMM presents a significant humanistic and economic burden [ 112 – 115 ]. Furthermore, hematologic AEs and infections—both associated with MM treatment—increase morbidity, mortality, and HCRU. Overall, RRMM care is costly, with high expenses from novel therapies—such as CAR T-cell therapy—and indirect costs such as productivity loss due to missed workdays for both patients and their caregivers [ 102 , 113 , 115 ]. Our research shows a significant data gap in understanding HCRU in the MENA region, with only five studies identified from the last 10 years [ 83 – 87 ]. A recent analysis of HCRU and treatment patterns of patients with MM across five European countries identified that patients who were triple-class exposed (i.e., previously treated with at least one PI, one anti-CD38 monoclonal antibody, and one IMiD) experienced higher HCRU than those who were not triple-class exposed, reflected by more inpatient hospitalizations and visits to healthcare professionals in the previous 12 months [ 116 ]. From the treatment patterns identified in this review, and the recommendations for early use of quadruplet regimens such as daratumumab + VRd in the recently published Saudi Myeloma Group and Turkish Society of Hematology treatment guidelines [ 48 , 49 ], it is likely that the number of patients with MM who are triple-class exposed in the MENA region will increase and add further economic strain to payors in the region.

Generic versions of bortezomib and lenalidomide have been approved for MM treatment in MENA. From the studies identified in this review, no clear differences in efficacy or safety were found between the branded and generic versions of these treatments, supporting their use as a more cost-effective alternative to branded products [ 50 , 56 , 57 , 62 ]. As health expenditures for MM continue to rise with the increasing development and costs of new treatments, as well as the increasing incidence of MM in the region, the need for cost-effective treatment options also increases. Consequently, the use of generic medications can be an area of cost savings that allows more patients to gain access to treatments [ 7 , 19 , 50 , 56 , 57 , 62 ]. Further studies with standardized designs and outcome assessments are warranted across MENA to elucidate the impact of MM on HCRU and inform appropriate strategies to lessen this impact on patients and healthcare systems.

Limitations

Our literature review had a number of limitations. The majority of the data retrieved were from retrospective studies and therefore susceptible to potential bias. While the countries included in the review were selected to represent the geographic and socioeconomic diversity of the MENA region, many countries in the region were not included. Further, the majority of studies reported data from single institutions and/or have limited patient numbers. Thus, these findings may not be fully representative of each country or the region as a whole. Inconsistencies existed in the reporting of data, particularly safety outcomes, owing to the reliance on real-world, retrospectively analyzed health records. Reporting on the cytogenetic profiles of patients with MM was inconsistent and limited, likely owing to variation in access to cytogenetic testing in the region. The lack of prospective, randomized controlled studies in the MENA region also restricted the degree to which conclusions can be drawn from this analysis.

Conclusions

Our review of the published literature identified a paucity of comprehensive data on the epidemiology and management of MM in the MENA region, complicating the implementation of fully informed clinical and health policy decisions. Currently, treatment patterns in the region do not reflect the recommendations in the latest international and regional treatment guidelines, highlighting a need to understand the factors behind this disparity. The burden of disease and treatment is particularly high in patients with RRMM, who face increasingly poor clinical outcomes with increasing LOTs. Improved understanding of the treatment patterns and HCRU in MENA may provide pathways to advancing access to newer therapies that can alleviate the disease and treatment burden of MM in the region.

Supplementary Information

Below is the link to the electronic supplementary material. Supplementary file 1 (PDF 536 KB)

Former workplace prior to recent retirement: Güner Hayri Özsan.

Medical Writing/Editorial Assistance

Medical writing support was provided by Joyce Lee, PhD, CMPP, and Tim Stentiford, CMPP, of Nucleus Global, an Inizio company, funded by GSK. Publication co-ordination support was provided by Jacqui Tan, CMPP, of Nucleus Global, an Inizio company, funded by GSK.

Authors Contributions

All authors (Meral Beksac, Mohamed Samra, Omar Abduljalil, Hasan AAL Yaseen, Sevgi Besisik, Guldane Cengi̇z Seval, Ashraf Elghandour, Gamal Fathy, Güner Hayri Özsan, Mahmoud Marashi, Ömür Gökmen Sevindik, Ruba Yaseen Ibrahim Taha, Bhumika Aggarwal, Jorge Mouro, and Abhay Phansalkar) made substantial contributions to the conception and design, acquisition of data or analysis and interpretation of data. All authors took part in drafting, revising or critically reviewing the manuscript; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. All authors meet the International Committee of Medical Journal Editors criteria for authorship for this article, take responsibility for the integrity of the work and have given their approval for this version to be published.

Funding

This study was funded by GSK (study ID: 300626). The journal’s Rapid Service Fee was funded by GSK.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflicts of Interest

Meral Beksac: honoraria from BMS, Janssen; consulting or advisory role from GSK, Takeda, Amgen, Janssen, and Menarini. Hasan AAL Yaseen: received honoraria from GSK, Amgen, Novartis, and Abbvie. Guldane Cengi̇z Seval: honoraria from BMS, Janssen, Amgen, Menarini, Pfizer, Takeda, and Sanofi; consulting or advisory role from GSK, Janssen, Menarini, Pfizer, BMS, Takeda, and Sanofi. Ashraf Elghandour: received payment/honoraria from J&J, AstraZeneca, Novartis, and Sanofi. Mahmoud Marashi: received payment for advisory board and lectures for Johnson & Johnson, Sanofi, Pfizer, Amgen, Abbvie, Eva Pharma, and Takeda. Bhumika Aggarwal, Jorge Mouro, Abhay Phansalkar: employees of GSK and hold financial equities in GSK. Mohamed Samra, Omar Abduljalil, Sevgi Besisik, Gamal Fathy, Güner Hayri Özsan, Ömür Gökmen Sevindik, and Ruba Yaseen Ibrahim Taha: none.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

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