Совершенствование усовершенствованной системы ухода за несколькими миеломами: понимание и реальные задачи, вытекающие из исследования ЭММИ.

Introduction

Multiple myeloma (MM) is a common hemopathy whose prognosis has significantly improved in the last decade. This is mainly due to the emergence of many new treatments which are more effective and better tolerated. However, despite this progress, MM patients eventually relapse and require multiple lines of treatment (LOT). Factors such as the patient’s comorbidities, previous treatments, and available options influence treatment choice. Therefore, managing patients receiving advanced LOT (four or more) remains a significant clinical challenge. 1 Numerous clinical trials in relapsed or refractory MM (RRMM) have demonstrated the clinical benefit of new agents like bispecific T-cell engagers and chimeric antigen receptor T-cells. 2–5 However, in the real- world, most patients with RRMM are not eligible for such trials, particularly those at more advanced lines. 6 Within an ever-evolving landscape of MM treatments, understanding the characteristics and real-life outcomes of these advanced-line patients is essential. However, there have been few real-world studies describing this population so far. To address this, we used the real-world French study EMMY (Epidemiology of Multiple MYeloma) 7,8 to determine the characteristics and outcomes of patients with MM receiving advanced LOT.

Materials and Methods

EMMY is a descriptive, multicenter, non-interventional, longitudinal cohort study conducted across 73 centers affiliated with the “Intergroupe Francophone du Myélome” (IFM). 7 It is registered in the French Health Data Hub (n° F20220518161845) and conducted in compliance with the principles of the Declaration of Helsinki. From 2017 to 2020, the study included patients who began a new treatment (irrespective of the treatment line) for symptomatic MM within a defined annual three-month period.

Patient data were extracted from medical records and collected at each center via an electronic case report form, then centralized within the study database. A scientific committee has conducted annual data quality control. Information on age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Staging System (ISS) score, presence of high-risk cytogenetic abnormalities (t(4;14) or a del(17p) mutation assessed using fluorescence in situ hybridization [FISH] analysis), data on prior treatments and refractoriness to these were gathered for each patient enrolled in the study. Annually, selected data on myeloma treatment, response, and medical history were retrospectively updated through 2021 at the time of the analysis.

This EMMY dataset was used to generate a cohort of patients receiving advanced LOT, in which all patients starting a fourth-line of treatment (L4) or beyond, during the different data collection periods, as well as those initially enrolled on a previous line of therapy who later received L4 or beyond during follow-up, were included.

Key endpoints were time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) defined from the time of the treatment initiation to the subsequent treatment line or death, disease progression or death, and death from any cause, respectively.

In a real-world setting, patient progression to a treatment line and response rate were assessed using a composite variable combining two complementary approaches: one based on physician judgment and documented treatment response, and another relying on monthly clinical and biochemical assessments aligned with the IMWG criteria. Progression was confirmed if either approach, or both, indicated disease progression. The best response rate was determined based on the best response identified from both approaches.

The Kaplan-Meier method was used to generate survival curves and estimate survival probabilities with their 95% confidence intervals (95% CI).

Results

Patient characteristics

From 2017 to 2020, 3616 patients were included in the EMMY study, as shown in Figure 1 . Among these patients, a L4 or beyond was initiated 2127 times. The patient distribution was as follows: 786 patients received L4, 585 a fifth-line (L5), 380 a sixth-line (L6), 231 a seventh-line (L7), and 145 an eighth-line treatment (L8). Baseline characteristics of the patients and their disease are detailed in Table 1 . At the initiation of L4, the median age was 72.7 years (range 27.8–94.8), and 426 patients (68.4%) had an ECOG PS score of 0 or 1. For Cohort L4, An 11-h , 35.7% of patients had high-risk cytogenetics, and 44.1% were classified as ISS stage III. The median time from diagnosis of MM to L4 was 53.9 months (range 4.3-322.6). An increasing proportion of patients with triple-class refractory (TCR) myeloma was observed across the lines: 24.4% in L4, 32.4% in L5, 55.8% in L6, 71.4% in L7, and 71.7% in L8. Similarly, refractoriness to lenalidomide and anti-CD38 monoclonal antibodies (mAbs) increased with the number of treatment lines.

Treatments

Among the enrolled patients, a diverse array of treatments was utilized, such as corticosteroids, proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), alkylating agents, mAbs, B-cell maturation antigen (BCMA)-targeted therapies, and various other combinations ( Figure S1 and Table S1 ). In L4, 363 patients received treatment combinations including a PI (46.2%), 346 including an IMiD (44%), 284 including an anti-CD38 mAb (36.1%), and 196 including an alkylating agent (24.9%). The most routinely used IMiD, anti-CD38 mAb, and PI were pomalidomide (31.3%), daratumumab (30.3%), and carfilzomib (22.9%), respectively. The most frequently used treatments evolved across the LOT, with a decrease in conventional MM therapies (PIs, IMiDs, anti-CD38 mAbs) and an increase in alkylating agents and innovative treatments such as BCMA-targeted therapies and B-cell lymphoma 2 inhibitors. For example, the use of pomalidomide decreased across the lines (31.3% in L4, 19.5% in L5, 10.3% in L6, 10.8% in L7, and 5.5% in L8), whereas the use of belantamab mafodotin increased (2.7% in L4, 6% in L5, 6.6% in L6, 10.4% in L7, and 17.9% in L8). For L4 patients, the most frequently received regimens were carfilzomib-dexamethasone (10.2%), pomalidomide-dexamethasone (9.4%), daratumumab-bortezomib-dexamethasone (9%), daratumumab-dexamethasone (6.9%), isatuximab-pomalidomide-dexamethasone (5.5%), daratumumab-pomalidomide-dexamethasone (5%), and pomalidomide-cyclophosphamide-dexamethasone (4.8%). An evolution in these regimens was also observed over the years of initiation of the line of interest ( Figure S2 ).

Outcomes

In L4, the median follow-up was 5.4 months (range 0-54.4). Within this cohort of 786 patients, the overall response rate (ORR) was 50.9% with 37.3% of patients achieving a very good partial response or better and 13.7% achieving a partial response. Fifty-three patients (7.4%) maintained stable disease, while 298 (41.7%) experienced primary progressive disease. The ORR declined progressively across LOT, reflecting a diminishing treatment efficacy with subsequent regimens: 44.3% in L5, 39.2% in L6, 39.2% in L7 and 33.9% in L8.

Among L4 patients, 556 (70.7%) discontinued treatments, primarily due to disease progression in 377 patients (48%) and side effects in 91 (11.6%). Among L4 patients, 388 (49.4%) received subsequent therapies and the median TTNT was 7.8 months (95% CI: 6.7-7.8) ( Figure 2 ). This time decreased across the LOT: 7 months (95% CI: 6-8.2) in L5, 5.1 months (95% CI: 4.3-6.1) in L6, 5.5 months (95% CI: 4.7-6) in L7, and 4.6 months (95% CI: 3.5-6) in L8.

The median PFS decreased with each subsequent line: 6.8 months (95% CI: 6-7.7) in L4, 5.8 months (95% CI: 4.8-6.6) in L5, 4 months (95% CI: 3.4-4.9) in L6, 4.7 months (95% CI: 3.9-5.3) in L7, and 4 months (95% CI: 2.8-5.3) in L8 ( Figure S3A ). The median OS was 19.4 months (95% CI: 17.4-22.5) in L4, decreasing to 15.1 months (95% CI: 13.4-16.9) in L5, 13.8 months (95% CI: 11.6-16.7) in L6, 14.5 months (95% CI: 11.3-18.7) in L7, and further reducing to 12.6 months (95% CI: 8.7-16.6) in L8 ( Figure S3B ).

Refractory status had a direct impact on patient survival in advanced-line therapies. In the overall cohort, the median PFS was 3.9 months (95% CI: 3.5-4.3) for patients who were TCR, compared to 6.9 months (95% CI: 6.3-7.7) for those who were not ( Figure 3A ). Similarly, median OS was 10 months (95% CI: 9.8-12.1) and 19.9 months (95% CI: 18.3-22.4), respectively ( Figure 3B ).

Discussion

Thanks to the growing availability of new treatments and the improved survival rates in MM, an increasing number of patients are receiving advanced LOT. The large-scale, multisite EMMY study presents a unique opportunity to gather real-world data, capturing the evolving therapeutic landscape and outcomes of over 2,000 patients undergoing L4 or beyond.

A strength of our study lies in the real-world data obtained from a large and homogeneous cohort, the patient characteristics of which were similar to other real-world analyses. 9,10 The representativeness of our population primarily stems from the EMMY study methodology, which ensures comprehensive patient inclusion, particularly for those in advanced-line treatment. However, our population is older and frailer than those in clinical trials. 2–5,11 For instance, in the phase 2 STORM study, 11 evaluating selinexor for TCR MM, the median age was 65.2 years, and 88% of patients had an ECOG PS score of 0 or 1. These differences underscore the discrepancy between clinical trials and real-world populations, and the high proportion of ineligible patients in advanced treatment lines. We identified a significant proportion of patients with high-risk features (high-risk cytogenetics, ISS stage III, TCR), highlighting the complexity of managing those who face numerous relapses.

We characterized the diversity and heterogeneity of real-world advanced-line treatment patterns. Indeed, no single treatment or combination of treatments was used preferentially. Similarly, the international LocoMMotion study, 10 a real-world, prospective study in triple-class exposed patients, reported 91 unique treatment regimens. Likewise, based on data from the French National Health Data System, Touzeau et al . 12 described the treatment patterns used for 12,987 patients with RRMM between 2014 and 2018. The heterogeneity of treatments was also observed starting from L3. The diversity, heterogeneity and scalability of treatment landscapes in advanced lines emphasize the complexity of managing this population, the absence of standard-of-care therapy and the necessity of personalized, case-by-case approaches. Moreover, we observed an evolution in treatments over successive lines and years of initiation, reflecting the continuous progress in the myeloma therapeutic arsenal and its rapid impact on managing our patients in advanced-line therapy.

Like other real-world studies, 10,13–15 we showed that advanced-line patients presented rapid disease progression, with median TTNT and PFS ranging from 7.8 months and 6.8 months in L4 to 4.8 months and 4 months in L8, respectively. Their outcomes remain poor, with median OS ranging from 19.4 months in L4 to 12.6 months in L8. Noticeably, the median PFS and TTNT in our study are very similar, underscoring the quality of the EMMY data and the accurate estimation of the incidence of disease progression in real-life settings. It is intriguing to compare our results with those of another French study 15 in which Leleu et al . reported a median TTNT of 5.7 months and a median OS of 16.1 months in L4. These different results can be explained by their earlier inclusion period (from 2013 to 2017) and emphasize the permanent need for more effective treatments at later lines. Additionally, like in other reports, 16,17 it should be noted that there are few treatment discontinuations due to side effects, despite advanced-line therapy. One possible explanation is that patients who tolerate therapy well are more likely to proceed to later LOT. Finally, similar to previous studies, 13,18 our analysis of patient outcomes underscored the relevance of refractory status, especially for TCR patients who have a poorer prognosis, with a median OS of 10 months.

It is important to note some limitations of our study. The retrospective design explains the absence of some data, such as quality of life assessments, which remain crucial for this population. Additionally, while we reported the overall treatment discontinuation rate due to adverse effects, we could not analyze toxicity by regimen due to the heterogeneity of treatments in this population. Furthermore, the study enrollment period (from 2017 to 2020) did not include novel therapies approved since 2020, such as BCMA-targeted therapies approved in France (teclistamab, elranatamab, and idecabtagene vicleucel). On subsequent evaluations, we will be able to measure the direct impact of these therapies on the real-world management of our patients.

Overall, the EMMY study provides us a deeper understanding of the characteristics, treatment landscape, and real-world outcomes of advanced-line patients. It demonstrates the heterogeneity and rapid evolution of the treatments used, as well as the poor prognosis of this population, emphasizing a real unmet medical need. The EMMY cohort could serve as a valuable benchmark for comparison with novel therapies approved from clinical trials and for assessing their impact in real-life settings.

Authors’ Contribution

Conceptualization: Titouan Cazaubiel, Cyrille Hulin, Olivier Decaux, Karim Belhadj-Merzoug, Margaret Macro, Aurore Perrot, Laure Vincent,; Methodology: Ronan Garlantézec, Titouan Cazaubiel, Cyrille Hulin, Olivier Decaux; Writing - original draft preparation: Titouan Cazaubiel, Cyrille Hulin, Olivier Decaux; Writing - review and editing: Titouan Cazaubiel, Cyrille Hulin, Olivier Decaux, Mohamad Mohty, Aurore Perrot, Laure Vincent, Margaret Macro, Bruno Royer, Denis Caillot, Arthur Bobin, Karim Belhadj-Merzoug, Lionel Karlin, Caroline Jacquet, Laurent Frenzel, Thomas Chalopin, Cécile Sonntag, Jean Fontan, Sophie Rigaudeau, Cyrille Touzeau, Hélène Demarquette, Abdelaziz Chaib, Clémence Santana, Stéphane Darre, Benoit Bareau, Ronan Garlantézec.

Competing Interests

Olivier Decaux declares receiving honoraria from Bristol Myers Squib (BMS), Gilead, GlaxoSmithKline (GSK), Janssen, Roche, Sanofi, and Takeda. Denis Caillot received honoraria from BMS. Arthur Bobin received honoraria from Johnson & johnson, sanofi, amgen, pfizer, stemline menarini. Karim Belhadj-Merzoug received honoraria, research funding, and traveling expenses from Amgen, BMS, Janssen, Pfizer, Sanofi, and Takeda. Margaret Macro received honoraria and research funding from Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Laure Vincent served on advisory board, or bibliographic presentations or writing of educational documents for Janssen, BMS, Takeda Sanofi. She received funding for congress expenses from Janssen, BMS, Sanofi, Pfizer, Takeda. Aurore Perrot served in a consulting or advisory role for Bristol Myers Squibb, Janssen, and Pfizer; and received research funding from Bristol Myers Squibb, Sanofi, and Takeda. Mohamad Mohty received honoraria, consultancy fees, and research funding from: Amgen, BMS, Gilead, GSK, Janssen, Jazz Pharmaceuticals, Novartis, Pfizer, Sanofi, Stemline Therapeutics, and Takeda. Lionel Karlin received honoraria from, served on advisory boards for, or received travel funding from AbbVie, Amgen, Janssen, Celgene/Bristol Myers Squibb, Pfizer, Sanofi, and Takeda. Laurent Frenzel received consulting fees and research funding from BioMarin, CSL Behring, Pfizer, Sobi, and Roche. Thomas Chalopin received honoraria and served in consulting role for BMS, Janssen, Sanofi, GSK, Stemline, Pfizer, Takeda. Cécile Sonntag received honoraria from, served on advisory boards for, or received travel funding from Amgen, Janssen, Celgene/Bristol Myers Squibb, Pfizer, Sanofi, and Takeda. Cyrille Touzeau served on advisory boards for and received honoraria from BMS, Amgen, Celgene, Janssen, Sanofi. Cyrille Hulin received honoraria from Janssen, Bristol Myers Squibb, Amgen, AbbVie, and Pfizer. The other authors have no competing interests to declare.

Ethical Conduct Approval – Helsinki – IACUC

The EMMY study is classified as research not involving human subject as defined in article L. 1121-1 of the French Public Health Code. This retrospective and prospective personal data study is being conducted in accordance with the Declaration of Helsinki and has been submitted to the French Health Data (N° F20220518161845) https://www.health-data-hub.fr/projets/emmy-epidemiologie-de-laprise-en-charge-therapeutique-du-myelome-multiple-en-france . No ethical approval for this study was required. All patients were informed about the processing of their data prior to enrolment in the study.

Informed Consent Statement

All authors and institutions have confirmed this manuscript for publication.

Supplementary Material

Improving Advanced-Line Multiple Myeloma Care: Insights and Real-World Challenges from the EMMY Study

Table S1. Treatments received by patients at each line

Figure S1 Class of drug received by patients at each line

Figure S2 Type of regimen and class of drug use in L4 depending on the year of line initiation

Figure S3 Progression free survival (A) and overall survival (B) in patients with advanced line therapy by treatment line

Acknowledgments

The authors acknowledge the teams of the 73 centers participating in EmmY, as well as the IFM project team, the Kappa Santé project team, the EmmY scientific committee, and the operational and steering committees of the EmmY consortium.

1 Treatment of relapsed and refractory multiple myeloma: Recommendations from the International Myeloma Working Group The Lancet Oncology Moreau P. Kumar S. K. Miguel J. S. Davies F. Zamagni E. Bahlis N. Ludwig H. Mikhael J. Terpos E. Schjesvold F. Martin T. Yong K. Durie B. G. M. Facon T. Jurczyszyn A. Sidana S. Raje N. Donk N. van de Lonial S. Richardson P. G.. 2021 22 3 e105 e118 10.1016/S1470-2045(20)30756-7 https://doi.org/10.1016/S1470-2045(20)30756-7 33662288

2 Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma New England Journal of Medicine Munshi N. C. Anderson L. D. Shah N. Madduri D. Berdeja J. Lonial S. Raje N. Lin Y. Siegel D. Oriol A. Moreau P. Yakoub-Agha I. Delforge M. Cavo M. Einsele H. Goldschmidt H. Weisel K. Rambaldi A. Reece D. San-Miguel J.. 2021 384 8 705 716 10.1056/NEJMoa2024850 https://doi.org/10.1056/NEJMoa2024850 33626253

3 Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): A phase 1b/2 open-label study The Lancet Berdeja J. G. Madduri D. Usmani S. Z. Jakubowiak A. Agha M. Cohen A. D. Stewart A. K. Hari P. Htut M. Lesokhin A. Deol A. Munshi N. C. O'Donnell E. Avigan D. Singh I. Zudaire E. Yeh T.-M. Allred A. J. Olyslager Y. Jagannath S.. 2021 398 10297 314 324 10.1016/S0140-6736(21)00933-8 https://doi.org/10.1016/S0140-6736(21)00933-8 34175021

4 Teclistamab in Relapsed or Refractory Multiple Myeloma New England Journal of Medicine Moreau P. Garfall A. L. Donk N. W. C. J. van de Nahi H. San-Miguel J. F. Oriol A. Nooka A. K. Martin T. Rosinol L. Chari A. Karlin L. Benboubker L. Mateos M.-V. Bahlis N. Popat R. Besemer B. Martínez-López J. Sidana S. Delforge M. Usmani S. Z. 2022 387 6 495 505 10.1056/NEJMoa2203478 https://doi.org/10.1056/NEJMoa2203478 35661166 PMC10587778

5 Elranatamab in relapsed or refractory multiple myeloma: Phase 2 MagnetisMM-3 trial results Nature Medicine Lesokhin A. M. Tomasson M. H. Arnulf B. Bahlis N. J. Miles Prince H. Niesvizky R. Rodrίguez-Otero P. Martinez-Lopez J. Koehne G. Touzeau C. Jethava Y. Quach H. Depaus J. Yokoyama H. Gabayan A. E. Stevens D. A. Nooka A. K. Manier S. Raje N. Mohty M.. 2023 29 9 2259 2267 10.1038/s41591-023-02528-9 https://doi.org/10.1038/s41591-023-02528-9 PMC10504075 37582952

6 Analysis of Common Eligibility Criteria of Randomized Controlled Trials in Newly Diagnosed Multiple Myeloma Patients and Extrapolating Outcomes Clinical Lymphoma Myeloma and Leukemia Shah J. J. Abonour R. Gasparetto C. Hardin J. W. Toomey K. Narang M. Srinivasan S. Kitali A. Zafar F. Flick E. D. Rifkin R. M. 2017 17 9 575 583.e2 10.1016/j.clml.2017.06.013 https://doi.org/10.1016/j.clml.2017.06.013 28886839

7 The EMMY longitudinal, cohort study: Real-world data to describe multiple myeloma management and outcomes as more therapeutic options emerge Clinical Hematology International Decaux O. Garlantézec R. Belhadj-Merzoug K. Macro M. Frenzel L. Perrot A. Moreau P. Royer B. Caillot D. Leleu X. Mohty M. Karlin L. Feugier P. Rigaudeau S. Fontan J. Sonntag C. Vincent L. Chalopin T. Loiseau H. A. Hulin C.. 2024 6 3 22 27 10.46989/001c.121371 https://doi.org/10.46989/001c.121371 39050939 PMC11268993

8 Real-Life Management of Patients Aged 80 Years Old and Over With Multiple Myeloma: Results of the EMMY Cohort Clinical Lymphoma Myeloma and Leukemia Chalopin T. Macro M. Decaux O. Royer B. Gounot R. Bobin A. Karlin L. Mohty M. Frenzel L. Perrot A. Manier S. Vincent L. Dib M. Slama B. Richez V. Allangba O. Zunic P. Newinger-Porte M. Mariette C. Hulin C.. 2024 10.1016/j.clml.2024.09.006 https://doi.org/10.1016/j.clml.2024.09.006 39462749

9 Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD The Oncologist Usmani S. Ahmadi T. Ng Y. Lam A. Desai A. Potluri R. Mehra M. 2016 21 11 1355 1361 10.1634/theoncologist.2016-0104 https://doi.org/10.1634/theoncologist.2016-0104 27486203 PMC5189616

10 LocoMMotion: A study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis) Leukemia Mateos M.-V. Weisel K. De Stefano V. Goldschmidt H. Delforge M. Mohty M. Dytfeld D. Angelucci E. Vincent L. Perrot A. Benjamin R. van de Donk N. W. C. J. Ocio E. M. Roccia T. Schecter J. M. Koskinen S. Haddad I. Strulev V. Mitchell L. Moreau P.. 2024 38 12 2554 2560 10.1038/s41375-024-02404-6 https://doi.org/10.1038/s41375-024-02404-6 39322709 PMC11588650

11 Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma New England Journal of Medicine Chari A. Vogl D. T. Gavriatopoulou M. Nooka A. K. Yee A. J. Huff C. A. Moreau P. Dingli D. Cole C. Lonial S. Dimopoulos M. Stewart A. K. Richter J. Vij R. Tuchman S. Raab M. S. Weisel K. C. Delforge M. Cornell R. F. Jagannath S.. 2019 381 8 727 738 10.1056/NEJMoa1903455 https://doi.org/10.1056/NEJMoa1903455 31433920

12 Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France—A cohort study using the French National Healthcare database (SNDS) Annals of Hematology Touzeau C. Quignot N. Meng J. Jiang H. Khachatryan A. Singh M. Taieb V. Chauny J.-V. Désaméricq G. 2021 100 7 1825 1836 10.1007/s00277-021-04522-y https://doi.org/10.1007/s00277-021-04522-y 33884454 PMC8195931

13 Outcomes of Patients with Multiple Myeloma Refractory to CD38-Targeted Monoclonal Antibody Therapy Leukemia Gandhi U. H. Cornell R. F. Lakshman A. Gahvari Z. J. McGehee E. Jagosky M. H. Gupta R. Varnado W. Fiala M. A. Chhabra S. Malek E. Mansour J. Paul B. Barnstead A. Kodali S. Neppalli A. Liedtke M. Narayana S. Godby K. N. Costa L. J.. 2019 33 9 2266 2275 10.1038/s41375-019-0435-7 https://doi.org/10.1038/s41375-019-0435-7 30858549 PMC6820050

14 Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study Clinical Lymphoma, Myeloma and Leukemia Mohty M. Terpos E. Mateos M.-V. Cavo M. Lejniece S. Beksac M. Bekadja M. A. Legiec W. Dimopoulos M. Stankovic S. Durán M. S. Stefano V. D. Corso A. Kochkareva Y. Laane E. Berthou C. Salwender H. Masliak Z. Pečeliūnas V. Ludwig H.. 2018 18 10 e401 e419 10.1016/j.clml.2018.06.018 https://doi.org/10.1016/j.clml.2018.06.018 30030033

15 Survival outcomes for patients with multiple myeloma in France: A retrospective cohort study using the Système National des Données de Santé national healthcare database European Journal of Haematology Leleu X. Gorsh B. Bessou A. Paka P. De Nascimento J. Colin X. Landi S. Wang P. F. 2023 111 1 125 134 10.1111/ejh.13976 https://doi.org/10.1111/ejh.13976 37199133

16 Multiple myeloma: Patient outcomes in real-world practice British Journal of Haematology Yong K. Delforge M. Driessen C. Fink L. Flinois A. Gonzalez-McQuire S. Safaei R. Karlin L. Mateos M.-V. Raab M. S. Schoen P. Cavo M. 2016 175 2 252 264 10.1111/bjh.14213 https://doi.org/10.1111/bjh.14213 27411022 PMC5096152

17 Real-World Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Record Review in France Advances in Hematology Lin H. M. Davis K. L. Kaye J. A. Luptakova K. Nagar S. P. Mohty M. 2019 2019 1 4625787 10.1155/2019/4625787 https://doi.org/10.1155/2019/4625787 30838045 PMC6374830

18 Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: A multicenter IMWG study Leukemia Kumar S. K. Dimopoulos M. A. Kastritis E. Terpos E. Nahi H. Goldschmidt H. Hillengass J. Leleu X. Beksac M. Alsina M. Oriol A. Cavo M. Ocio E. M. Mateos M. V. O'Donnell E. K. Vij R. Lokhorst H. M. van de Donk N. W. C. J. Min C. Durie B. G. M.. 2017 31 11 2443 2448 10.1038/leu.2017.138 https://doi.org/10.1038/leu.2017.138 28620163

Data Availability Statement

All are available upon reasonable request.