Реальные модели лечения и результаты лечения пациентов с множественной миеломой, инициирующих эгранатамаб: результаты ALTITUDE-1 и ALTITUDE-2 Ретроспективные когортные исследования.

Introduction

Multiple myeloma (MM) is a hematological malignancy that originates in plasma cells within the bone marrow [ 1 ]. The incidence of multiple myeloma was 6.7 per 100,000 people in the United States (US) in 2022, while the 5-year relative survival from 2015 to 2021 was 62% [ 2 ]. The core treatment classes typically used for treatment of MM include proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), which have substantially increased the survival of patients with MM since their introduction [ 3–5 ]. However, most patients with MM will eventually develop relapsed or refractory disease [ 6 ]. For these patients, several additional options have recently become available, including chimeric antigen receptor T-cell (CAR T) therapies and bispecific antibodies (BsAbs) [ 7–10 ].

Elranatamab is a B-cell maturation antigen (BCMA)-directed BsAb indicated in the US for the treatment of patients with relapsed/refractory MM who have previously received at least four prior lines of therapy, including a PI, IMiD, and an anti-CD38 mAb. Elranatamab was approved based on the results from the MagnetisMM-3 trial ( NCT04649359 ), a phase II trial aimed at assessing the safety and efficacy of elranatamab monotherapy [ 11 ]. Patients in the MagnetisMM-3 trial received subcutaneous elranatamab 76 milligrams (mg) once weekly (QW) in 28-day cycles, following two step-up priming doses of 12 mg and 32 mg on days 1 and 4 of cycle 1. After six cycles, patients with a sustained response (partial response or better for at least 2 months) transitioned to dosing every 2 weeks (Q2W), and then to every 4 weeks (Q4W) after completing six cycles on the Q2W schedule. The recently published results of the MagnetisMM-3 trial, based on 33.9 months of follow-up data, reported an objective response rate (ORR) of 61.0%, with 37.4% of patients achieving complete response or better. The median progression-free survival (PFS) was 17.2 months (95% confidence interval [CI] 9.8–not-estimable [NE]) and the median overall survival (OS) was 24.6 months (95% CI, 13.4–NE). Further, among responders, the median duration of response (DOR) was not reached, and the probability of maintaining response at 24 months was 66.9% (95% CI, 54.4–76.7) [ 12 ]. Among those with a complete response or better, the median DOR was also not reached, and the probability of maintaining response at 30 months was 79.1% (95% CI, 62.1–89.0) [ 13 ]. Key safety events included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections [ 13 ].

Published real-world (RW) data on elranatamab remain limited since its approval. Portuguese et al. (2025) studied N = 130 patients treated with commercially available elranatamab as part of a multi-study in the US reporting an ORR of 65% and safety profile similar to that of MagnetisMM-3, albeit with elevated rates of ICANS [ 14 ]. Additional multicenter studies have also been recently presented based on elranatamab use in the UK [ 15 ] and across multiple countries [ 16 ]. Here, we describe the results from two non-interventional studies in the US: The Administration of Elranatamab In the Real-World: Treatment Patterns, Healthcare Resource Utilization, Costs, Effectiveness, and Safety (ALTITUDE-1 [EUPAS1000000229] and ALTITUDE-2 [EUPAS1000000293]). This analysis focuses on the RW patient profile, dosing and administration patterns, and effectiveness associated with elranatamab in the US following its approval.

Methods

Data sources

To allow for representation across a diverse patient population, data were collected from two distinct databases: Komodo Health’s Healthcare Map TM (ALTITUDE-1), a commercial and Medicare-based dataset, and Medicare’s Fee-For-Service (FFS) dataset (ALTITUDE-2). The analyses and results were performed and reported separately for each dataset. Komodo Health’s Healthcare Map TM is an integrated open- and closed-claims database that encompasses longitudinal records detailing medical procedures, diagnoses, treatments, associated costs within the healthcare system, and patient characteristics and outcomes such as race/ethnicity, ZIP code, and all-cause mortality records. Medicare FFS is a claims-based dataset that represents patients in the US who are over the age of 65 or have certain conditions, such as kidney failure or certain disabilities. This database encompasses inpatient and outpatient diagnoses, procedures, devices, and medication information in the form of alphanumeric codes, dates of service, charged amounts, paid claims, and a limited number of provider characteristics, including provider number and geographic information (state, county, and ZIP code). These databases have been used in prior studies, including specifically in MM [ 17 , 18 ]. ALTITUDE-1 and ALTITUDE-2 were secondary research on previously collected de-identified data with no way to trace back or identify individuals. Given these considerations, each study received an institutional review board (IRB) exemption (WCG IRB, Cary, NC; Advarra IRB, Columbia, MD), and no informed consent was required.

Study population

Analyses of ALTITUDE-1 and ALTITUDE-2 included adult (≥18 years old) patients with a diagnosis of MM whose first prescription or medical claim with national drug code (NDC), healthcare common procedure coding system (HCPCS), 10th revision of the International Classification of Diseases (ICD-10) code, or generic name for elranatamab (index date) occurred after 14 August 2023 (US approval date). Eligible patients were required to have at least 180 days of pre-index continuous closed-claims medical coverage and no prior use of any other BCMA-directed BsAb used for the treatment of MM. ALTITUDE-2 also required 30 days of continuous closed-claims coverage after the index date and excluded patients if they were enrolled in Medicare Advantage during the study period or were older than 115 on the index date. The study period for these interim analyses ended on 28 October 2025 for ALTITUDE-1 and 30 September 2025 for ALTITUDE-2. Patients were indexed on the date of elranatamab initiation and followed until the earliest of death, the end of the study period, or the end of continuous enrollment (unless otherwise noted).

Study variables

Patient characteristics evaluated at baseline included age, sex, and race/ethnicity. Comorbidities were assessed during the 180 days prior to and including the index date. Pre-index clinical and MM treatment history were assessed from the date of MM diagnosis until 1 day prior to the index date. All study variables were defined using diagnostic codes, including ICD-10 diagnosis/procedure codes, CPT/HCPCS procedure codes, NDC for medications, and generic names for medications.

Treatment patterns included the use of supportive medications (acetaminophen, corticosteroids, and diphenhydramine) which are used to manage the risk of CRS, based on the United States Package Insert (USPI). The ALTITUDE-2 study also included tocilizumab as part of the definition of supportive medications. Assessments for the total number of elranatamab claims reported overall and by reported vial size (both a 44 mg and 76 mg vial size are available for elranatamab, with the former intended for use during the step-up dosing period). The frequency of elranatamab claims was estimated based on the total number of inpatient (IP), non-IP, and pharmacy claims during the follow-up period. Vial size was identified through NDC codes: 76 mg/1.9 mL (00069-4494-01 and 00069-4494-02), 44 mg/1.1 mL (00069-2522-01 and 00069-2522-02), and the quantity reported for claims not captured through NDC codes. Vial size was not available for claims in the inpatient setting or claims in a non-inpatient non-pharmacy setting that did not report a quantity.

Three a priori time periods were created within the data to best align with the US label [ 19 ] and results were reported separately for each of these periods: 1) the step-up dosing period (Day [D] 1–8), where patients would be expected to receive a 12 mg dose, a 32 mg dose (both most likely from the 44 mg vial), and their first full dose of 76 mg; 2) maintenance period 1 (D9-D168), where patients would be expected to be using elranatamab 76 mg weekly (QW) regardless of their response; and 3) maintenance period 2 (D169+), where patients could switch to a biweekly (Q2W) dosing schedule if they achieved a partial response or better for 2 consecutive months [ 19 ]. For each patient, the time between administrations was estimated as the sum of the days between claims (inclusive) for elranatamab divided by the total number of administrations within each period among patients with at least two claims for elranatamab.

The number of days between doses during each maintenance period (D9-D168 and D169-D365) was separately applied to estimate the total number of vials a patient would be expected to use if they stayed on treatment for the entire year. The annualized number of vials was calculated by summing estimated vial usage across the three treatment periods. For the step-up dosing period, vial use was assumed to follow the per-label dosing, as inpatient administration may be underreported in the data (i.e., we assumed each patient received three vials). For the first and second maintenance periods (D9-D168 and D169-D365), the mean number of days between doses was used to estimate the number of vials administered during each period. The estimated vials from all three periods were then combined to determine the annualized total. These annualized vial usage estimates were then descriptively compared to the annual vial usage reported from the MagnetisMM-3 trial data and that would be expected per the USPI [ 19 ].

Effectiveness outcomes included time-to-next-treatment or death (TTNT/D) (serving as a proxy for progression-free survival) and overall survival (OS). TTNT/D was assessed as the time in months from index date until a switch to a new treatment or death and OS was assessed as the time in months from index date to death.

Statistical analysis

This study was descriptive in nature, and no formal statistical comparisons were performed either within or across studies/datasets. Dichotomous and categorical variables were summarized by the number and percentage of patients in each category. Continuous variables were described using mean (standard deviation [SD]), median (interquartile range [IQR]), minimum, and maximum. If applicable, the frequency and percentage of patients with missing data for each variable were described. Per Centers for Medicare & Medicaid Services (CMS) suppression policies, which govern the Medicare FFS data used in ALTITUDE-2, cell counts >0 but <11 were reported as “<11.”

TTNT/D and OS were assessed using unadjusted Kaplan–Meier methods. The median time to event in months was reported along with the 95% confidence interval (CI) which was calculated using a log–log transformation. In the case of both outcomes, patients without an event were censored at the earliest of the end of continuous closed-claim coverage or the end of data. Landmark analyses were also conducted to estimate the percentage of patients at both 12 and 18 months who would be alive and not have initiated a new therapy (based on the TTNT/D Kaplan–Meier curve) and who would be alive (based on the OS Kaplan–Meier curve).

Results

Patients

In the ALTITUDE-1 population from the insurance claims database, 183 patients initiated elranatamab and met all the selection criteria ( Table 1 ). The median follow-up was 7.3 months [IQR: 2.4, 10.9]. Among patients with available demographic data, the median age was 73, 50.8% were male, while 47.5% were White and 26.8% were Black ( Table 2 ). Regional representation was highest in the South (46.4%), followed by the Northeast (23.0%). In the 6 months before treatment, the mean Charlson Comorbidity Index (CCI) score was 5.1, with 52.5% having a CCI score of 5 or higher. No patients in ALTITUDE-1 had a history of plasma cell leukemia, but 2 (1.1%) had reported graft-versus-host disease (GVHD), while 27 (14.8%) patients had concurrent amyloidosis. The most common nonmalignant comorbidities were renal disease (45.9%), congestive heart failure (26.2%), and chronic pulmonary disease (24.6%). The mean time since initial MM diagnosis was 68.6 months. The majority of patients (82.0%) were triple-class exposed and nearly half (43.2%) were penta-drug exposed. Thirty-two patients (17.5%) were BCMA-exposed before elranatamab initiation (11.5% due to BCMA-directed CAR T therapies and 7.7% due to belantamab mafodotin) and 4.4% had prior treatment with talquetamab. Table 1. Study attrition for ALTITUDE-1 and ALTITUDE-2. ALTITUDE-1 ALTITUDE-2 Eligibility criteria N remaining % lost N remaining % lost Inclusion criteria Prescription claim or medical claim of elranatamab during the index identification period (index date) 855 639 Age 18 or older on index date 848 –<1% 639 −0% Diagnosis of multiple myeloma any time prior to index date 848 −0% 613 −4% 180 days of closed medical and pharmacy claims enrollment prior to index date and 30 days after the index date for ALTITUDE-2 196 −77% 430 −30% Exclusion criteria Enrollment in Medicare Advantage at any point during the study period NA NA 409 −5% Age above 115 years old on the index date NA NA 409 −0% Previous prescription claim or medical claim of teclistamab 183 −7% 391 −4% Total Patients 183 391 Table 2. Baseline demographics, clinical characteristics, and treatment characteristics of patients initiating elranatamab from ALTITUDE-1 and ALTITUDE-2. Characteristic ALTITUDE-1 N = 183 ALTITUDE-2 N = 391 Age on index date Mean (SD) 71.2 (10.4) 74.6 (8.03) Median [IQR] 73.0 [65.0, 78.0] 75.0 [70.0, 80.0] Min, Max 25.0, 89.0 47.0, 94.0 Sex, n (%) Male 93 (50.8%) 208 (53.2%) Female 81 (44.3%) 183 (46.8%) Unknown or missing 9 (4.9%) 0 (0.0%) Race/Ethnicity, n (%) White 87 (47.5%) 291 (74.4%) Black 49 (26.8%) 49 (12.5%) Asian/Pacific Islander 2 (1.1%) <11 Hispanic or Latino 29 (15.8%) 25 (6.4%) Other 7 (3.8%) <11 Unknown or missing 9 (4.9%) <11 Region, n (%) Northeast 42 (23.0%) 114 (29.2%) Midwest 27 (14.8%) 62 (15.9%) West 29 (15.8%) 75 (19.2%) South 85 (46.4%) 140 (35.8%) Care setting on index date a , n (%) Inpatient 81 (44.3%) 275 (70.3%) Outpatient 55 (30.1%) 116 (29.7%) Pharmacy 4 (2.2%) NR Unknown or missing 43 (23.5%) 0 (0.0%) Time from initial MM diagnosis to index date (months) Mean (SD) 68.6 (32.7) 66.5 (32.6) Median [IQR] 71.7 [38.3, 97.4] 69.0 (39.0, 98.0) Min, Max 0.2, 118.3 0.0, 114.0 Prior treatment history, n (%) Triple class exposed b 150 (82.0%) 291 (74.4%) Penta-drug exposed c 79 (43.2%) 129 (33.0%) HSCT 80 (43.7%) 211 (54.0%) BCMA-directed therapy 32 (17.5%) 82 (21.0%) BCMA CAR-T therapy 21 (11.5%) 64 (16.4%) Talquetamab 8 (4.4%) 28 (7.2%) Comorbidities at baseline, n (%) Any infection 169 (92.3%) 367 (93.9%) Hypertension 164 (89.6%) 338 (86.4%) Peripheral neuropathy 139 (76.0%) 294 (75.2%) Neutropenia 133 (72.7%) 233 (59.6%) Use of IV anti-infective 121 (66.1%) 237 (60.6%) Any non-hematological neoplasm 90 (49.2%) 196 (50.1%) Other hematological malignancies 71 (38.8%) 107 (27.4%) Hypercalcemia 68 (37.2%) 116 (29.7%) Extramedullary disease 22 (12.0%) 29 (7.4%) Amyloidosis 27 (14.8%) 74 (18.9%) Graft vs host disease 2 (1.1%) <11 Bone lesions 9 (4.9%) 23 (5.9%) Plasma cell leukemia 0 (0.0%) 43 (11.0%) Hepatotoxicity 1 (0.5%) <11 Charlson comorbidities d Categorical CCI score, n (%) 0 (no comorbidities) 1 (0.5%) 52 (13.3%) 1 to 2 (mild) 39 (21.3%) 202 (51.7%) 3 to 4 (moderate) 47 (25.7%) 116 (29.7%) ≥5 (severe) 96 (52.5%) 21 (5.4%) CCI comorbidities in baseline, n (%) Metastatic solid tumor 60 (32.8%) 93 (23.8%) Congestive heart failure 48 (26.2%) 119 (30.4%) Renal disease 84 (45.9%) 157 (40.2%) Chronic pulmonary disease 45 (24.6%) 106 (27.1%) Diabetes 51 (27.9%) 100 (25.6%) Peripheral vascular disease 39 (21.3%) 81 (20.7%) Cerebrovascular disease 21 (11.5%) 48 (12.3%) Myocardial infarction 17 (9.3%) 36 (9.2%) Liver disease 13 (7.1%) 36 (9.2%) Hemiplegia/paraplegia 5 (2.7%) 11 (2.8%) Rheumatic disease 4 (2.2%) 19 (4.9%) Peptic ulcer disease 5 (2.7%) <11 Dementia 16 (8.7%) 39 (10.0%) HIV 0 (0.0%) <11 Duration of follow-up (months) Median [IQR] 7.3 [2.4, 10.9] 8.0 [3.8, 13.3] Abbreviations: BCMA = B Cell Maturation Antigen, CAR T-cell = Chimeric Antigen Receptor T Cell Therapy, CCI = Charlson Comorbidity Index, CD38 = Cyclic ADP Ribose Hydrolase, ER = Emergency Room, HIV = Human Immunodeficiency Virus, HSCT = Hematopoietic Stem Cell Transplantation, IMiDs = Immunomodulatory Drugs, IQR = Interquartile Range, IV = Intravenous, IVIG = Intravenous immunoglobulin, mAbs = Monoclonal antibodies, MM = Multiple Myeloma, NR = Not Reported, PI = Proteasome Inhibitors, SD = Standard Deviation. a. Inpatient = Any observations in the inpatient table or observations in the non-inpatient table with an inpatient place of service; Outpatient = Any observation in the non-inpatient table with an outpatient place of service. b. Triple-class exposed: exposed to at least 1 proteasome inhibitors, at least 1 immunomodulatory agent, and at least 1 CD38 monoclonal antibody. c. Penta-class exposed: exposed to 2 unique proteasome inhibitors, 2 unique immunomodulatory agents, and at least 1 CD38 monoclonal antibodies. d. Assessed from 180 days prior to index date to index date. Note: Per Centers for Medicare & Medicaid Services (CMS) suppression policies – which govern the Medicare FFS data with cell counts >0 but <11 must be masked and is reported as “<11”.

In the ALTITUDE-2 population from the Medicare FFS dataset, 391 patients initiated treatment with elranatamab and met all of the selection criteria ( Table 1 ). The median follow-up time was 8.0 months [IQR: 3.8, 13.3]. The demographic and clinical characteristics were similar to ALTITUDE-1. The median age was 75 years, 53.2% of patients were male, 74.4% were White, and 12.5% were Black ( Table 2 ). The most common region was the South 35.8%), followed by the Northeast (29.2%). Most patients had a CCI score of 1 or 2 (51.7%). Histories of plasma cell leukemia and concurrent amyloidosis were noted in 43 (11.0%) and 74 (18.9%) patients, respectively. The most common nonmalignant comorbidities were renal disease (69.6%), congestive heart failure (30.4%), and diabetes (25.6%). The mean time since initial MM diagnosis was 66.5 months. Nearly three-fourths were triple-class exposed (74.4%) and a third were penta-drug exposed (33.0%). Over a fifth (21.0%) of patients were BCMA-exposed before elranatamab initiation (16.4% due to BCMA-directed CAR T therapies) ( Table 2 ).

Treatment patterns

Of the 183 patients in ALTITUDE-1, 30.1% ( n = 55) were treated in an outpatient setting on the index date. Supportive medications (defined as acetaminophen, corticosteroids, diphenhydramine) were used by 52.5% of patients during the step-up period, though it is not fully known whether these occurred before or after the administration of elranatamab ( Table 3 ). The results from ALTITUDE-2 were generally similar. On the index date, 29.7% of patients received care in the outpatient setting. Supportive medications (which included acetaminophen, corticosteroids, diphenhydramine, as well as tocilizumab) were used by 53.7% of patients during the step-up period ( Table 4 ). Table 3. Dosing and administration patterns of patients receiving elranatamab in ALTITUDE-1 (Komodo Health’s Healthcare Map™ database). Follow-up periods Index date Index date to end of follow-up Step-up period D1-8 First maintenance period D9-168 Second maintenance period D169+ N 183 181 181 147 47 Use of supportive medication a , n (%) 69 (37.7%) NR 96 (52.5%) NR NR Number of elranatamab claims 186 1,948 297 1,228 423 Vial size b , n (%) Inpatient claim (No dose) 80 (43.0%) 107 (5.5%) 88 (29.6%) 18 (1.5%) 1 (0.2%) 44 mg/1.1 mL 22 (11.8%) 153 (7.9%) 42 (14.1%) 78 (6.4%) 33 (7.8%) 76 mg/1.9 mL 52 (28.0%) 1,344 (69.0%) 110 (37.0%) 919 (74.8%) 315 (74.5%) Missing dose/unknown vial size 32 (17.2%) 344 (17.7%) 57 (19.2%) 213 (17.3%) 74 (17.5%) Time between administrations (days) c ≥2 administrations during the time period, n (%) NR 156 (86.2%) 92 (50.8%) 127 (86.4%) 43 (91.5%) Mean (SD) NR 13.07 (12.34) 5.17 (2.0) 10.4 (7.8) 20.6 (13.0) Median [IQR] NR 7.0 [7.0, 14.0] 6.0 [3.0, 7.0] 7.0 [7.0, 14.0] 14.0 [14.0, 28.0] Min, Max NR 1.0, 184.0 1.0, 7.0 1.0, 92.0 6.0, 127.0 Abbreviations: D = Day, IQR = Interquartile Range, mg = Milligrams, mL = Milliliter, NR = Not Reported, SD = Standard Deviation. a. Use of supportive medication includes acetaminophen, dexamethasone, and diphenhydramine. b. Reported as numbers of claims for specific vial size and percentage of total elranatamab claims during the time period. c. Assessed among those with at least two administrations for elranatamab during the time period of interest. Table 4. Dosing and administration patterns of patients receiving elranatamab in ALTITUDE-2 (Medicare FFS database). Follow-up periods Index date to end of follow-up Step-up period D1-8 First maintenance period D9-168 Second maintenance period D169+ N 391 391 332 135 Use of supportive medication a , n (%) 357 (91.3%) 210 (53.7%) 230 (69.3%) 77 (57.0%) Number of elranatamab claims 4680 681 2959 1040 Vial size b , n (%) Inpatient claim (No dose) 301 (6.4%) 282 (41.4%) 16 (0.5%) 0 (0.0%) 44 mg/1.1 mL 216 (4.6%) 71 (10.4%) 96 (3.2%) 49 (4.7%) 76 mg/1.9 mL 2924 (62.5%) 220 (32.3%) 2000 (67.6%) 704 (67.7%) Missing dose/unknown vial size 1239 (26.5%) 108 (15.9%) 847 (28.6%) 284 (27.3%) Time between administrations (days) c Mean (SD) 12.8 (13.6) 4.1 (1.8) 10.8 (7.9) 20.9 (22.1) Median [IQR] 7.0 [7.0, 14.0] 4.0 [3.0, 5.0] 7.0 [7.0, 14.0] 14.0 [14.0, 28.0] Abbreviations: D = Day, IQR = Interquartile Range, mg = Milligrams, mL = Milliliter, SD = Standard Deviation. a. Use of supportive medication includes acetaminophen, dexamethasone, diphenhydramine, and tocilizumab. b. Reported as numbers of claims for specific vial size and percentage of total elranatamab claims during the time period. c. Assessed among those with at least two administrations for elranatamab during the time period of interest. Note: Per Centers for Medicare & Medicaid Services (CMS) suppression policies – which govern the Medicare FFS data with cell counts >0 but <11 must be masked and is reported as “<11”.

During the step-up period (D1-8), 50.8% ( n = 92) of the patients from ALTITUDE-1 received at least two doses of elranatamab, with a mean interval of 5.2 days (median 6.0 days) between doses ( Table 3 ). The mean time between elranatamab claims in ALTITUDE-2 during the step-up period was slightly shorter at 4.1 days (median = 4.0 days) ( Table 4 ).

During the first maintenance period (D9-168), 147 patients from ALTITUDE-1 contributed 1228 elranatamab claims; 127 patients (86.4%) had two or more elranatamab administrations or pharmacy claims with a mean interval of 10.4 days between doses (median 7.0 days; IQR: 7, 14). However, a quarter of the administrations occurred at a Q2W dosing interval. The results from ALTITUDE-2 were similar. Based on 332 patients who contributed 2959 claims, the mean interval between elranatamab claims was 10.8 days (median 7.0 days; IQR: 7, 14). Further details are summarized in Tables 3 and 4 .

During the second maintenance period (D169+), a total of 47 and 135 patients contributed to 423 and 1040 claims, respectively, in ALTITUDE-1 and −2. In ALTITUDE-1, there was a mean of 20.6 days (median = 14.0 days; IQR: 14, 28) between administrations with approximately a quarter of administrations on a Q4W cadence ( Table 3 ). The results for ALTITUDE-2 were similar in that there was a mean of 20.9 days (median = 14.0 days; IQR: 14, 28) between administrations with approximately a quarter of administrations on a Q4W cadence ( Table 4 ).

Overall vial usage

Strictly adhering to the USPI, a patient who remains on elranatamab for a full year would be expected to use 39 vials ( Figure 1 ). This was calculated by assuming three vials used during the step-up dosing period, QW administrations through Cycle 6 (i.e., 7 days between administrations), and Q2W administrations for the rest of the year (i.e., 14 days between administrations). We compared this vial usage with what was observed in ALTITUDE-1 and ALTITUDE-2, replacing the days between administrations for each maintenance period with the observed mean dosing intervals as reported above (maintenance period 1: 10.4 and 10.8 days, respectively, for ALTITUDE-1 and ALTITUDE-2; maintenance period 2: 20.6 and 20.9 days). With these assumptions, vial usage ranged from 27.9 vials (ALTITUDE-1) to 27.1 vials (ALTITUDE-2) ( Figure 1 ). Observed data from MagnetisMM-3 trial ranged from 20.0 vials for all patients ( N = 187) to 29.1 vials for patients who achieved a partial response or better ( N = 97). Figure 1. Projected vial usage within the first year of elranatamab. X-axis label: Number of vials, unit: vials. X-axis range: 0 to 45 vials, with tick labels at 0, 5, 10, 15, 20, 25, 30, 35, 40, 45. Y-axis label: data source, unit: (not applicable). Y-axis categories and bar values: Per USPI with Q2W switch as early as recommended equals 39.0. Observed MagnetisMM-3 trial (N=187) equals 20.0. Observed MagnetisMM-3 trial (partial response or better; N=97) equals 29.1. ALTITUDE-1 projections equals 27.9. ALTITUDE-2 projections equals 27.1. Footnote text: For the step-up period, vial use was assumed to follow the per-label dosing, as inpatient administration may be underreported in the data (i.e., each patient received 3 vials). For the first and second maintenance periods (D9-D168 and D169-D365), the mean number of days between doses was used to estimate the number of vials administered during each period. The estimated vials from all three periods were then combined to determine the annualized total. Abbreviation note: PR equals Partial Response, USPI equals United States Prescribing Information. The detailed data points are as follows: - For the scenario Per USPI with Q2W switch as early as recommended, the number of vials is 39.0. - For the scenario Observed MagnetisMM-3 trial (all patients; N equals 187), the number of vials is 20.0. - For the scenario Observed MagnetisMM-3 trial (PR or better; N equals 97), the number of vials is 29.1. - For the scenario ALTITUDE-1 projections, the number of vials is 27.9. - For the scenario ALTITUDE-2 projections, the number of vials is 27.1. A horizontal bar graph showing projected and observed elranatamab vial usage across studies.

Effectiveness

In ALTITUDE-1, neither the median TTNT/D nor the median OS was reached (for both, 95% CI: NE, NE). Based on the Kaplan–Meier curve, landmark analyses estimated 68.0% and 66.0% of patients at 12 and 18 months, respectively, were alive and had not initiated a new therapy. Additionally, 74.4% and 70.0% of patients (respectively) would be alive. Similarly, in ALTITUDE-2, the median TTNT/D was not reached (95% CI: 18.7 months, NE). Landmark analyses estimated that 62.0% and 57.7% of patients at 12 and 18 months, respectively, were alive and had not initiated a new therapy. The median OS was also not reached (95% CI: 21.0 months, NE). Landmark analyses estimated 66.2% of patients alive at 12 months and 60.7% of patients alive at 18 months.

Discussion

Although prior literature has integrated elranatamab clinical trial data from MagnetisMM-3 with RW data for the purposes of facilitating efficacy comparisons and estimating budget impact and the cost of care [ 20–24 ], RW data specific to elranatamab are limited. To our knowledge, these are the first studies reporting on the RW treatment patterns associated with elranatamab among US patients with MM. Cirstea et al. studied 43 patients who received elranatamab at Massachusetts General Hospital as part of either inpatient step-up dosing or a newly implemented Bispecific Outpatient Safe Step-Up (BOSS) program; however, the results focused on safety events [ 25 ]. Additionally, a few multicentered studies have recently been presented [ 14–16 ] though they did not report detailed treatment pattern results along with their clinical outcomes. As such, our data provides early insights into the use of elranatamab within routine clinical practice in the US. Patients in ALTITUDE-1 and ALTITUDE-2 were slightly older (70 and 75 years, respectively) than reported in the MagnetisMM-3 trial (68 years) [ 11 ], though comparable to Portuguese et al.’s and Cirstea et al.’s US studies (71–74 years, depending upon the subgroup) [ 25 ]. It is also worth noting the relatively higher percentages of Black patients in the ALTITUDE studies (26.8% and 12.5%, respectively) compared with other elranatamab studies, clinical or RW (e.g., 7.3% in MagnetisMM-3 [ 11 ]).

Rates of prior penta-class exposure were lower in the ALTITUDE studies (46.4% and 34.6%) compared with the MagnetisMM-3 trial (70.7%) though 20–30% of patients in the ALTITUDE studies had received prior commercial BCMA-targeted therapies. In contrast, all patients from Cohort A of the MagnetisMM-3 trial were BCMA naïve. Additionally, although patients with concurrent AL amyloidosis were excluded from the MagnetisMM-3 trial, our study demonstrates that these patients comprise 10–20% of all elranatamab-treated patients in RW practice. Several case series have demonstrated the safety and efficacy of BCMA-targeted BsAb therapy in these patients [ 26–30 ].

With respect to treatment patterns, our data suggested significant adoption of outpatient elranatamab during the step-up period (approximately 30%), though there is a risk that the data may have included misclassifications wherein a hospital site was defined as outpatient for billing purposes but would otherwise be considered to be inpatient. Regardless, the adoption of outpatient step-up dosing for BsAb therapy may rise in coming years, both due to recent publications of best practices for ambulatory step-up dosing [ 25 , 31 ] as well as the increasing adoption of prophylactic tocilizumab [ 32 , 33 ] and recent NCCN guidelines [ 10 ]. Although tocilizumab use was collected in the ALTITUDE-2 study, the chronology of drug administration was not sufficiently sensitive to determine whether any of this usage was prophylactic or as a treatment for CRS if the claims for both occurred on the same day. It is also worth noting that the rates of supportive care were lower than might be expected based on the USPI. It is unclear whether this reflects a limitation of the data capture (e.g., acetaminophen is being used but that usage is not reflected in the claims data) or actual clinical practice. More research using data sources which can differentiate between CRS prophylaxis and treatment is necessary.

During the two maintenance periods that roughly comprised 6 months each, both data sources suggested less frequent elranatamab administration than would be expected per the USPI at the time of the study. While the median dosing interval in ALTITUDE-2 aligned with label expectations (i.e., 7 days between administrations from the post-SUD period through Cycle 6 and 14 days afterward), the mean interval (10.8 and 20.9 days, respectively) suggested that a significant subset of patients (approximately 25% of patients) followed an extended dosing schedule. This was also seen among patients in ALTITUDE-1, where Q2W dosing was observed well before Cycle 7. Q4W dosing was commonly observed in both databases even though this schedule was not listed in the elranatamab USPI at the time of data extraction. A recent update to the USPI allows for Q4W dosing starting at Week 49 among patients who have maintained the response following 24 weeks of treatment at the Q2W dosing schedule [ 19 ]. These results are in line with other RW database studies that suggest a less frequent dosing schedule over time with BsAbs in RW practice [ 27 ].

Although patients strictly adhering to the USPI would be expected to use 39 vials over the course of their first year of treatment, the RW experience suggests significantly fewer vials (27–28 vials) because of this less frequent dosing. Possible reasons for elranatamab dose de-escalation may have included toxicity management (e.g., infections). Given the significant comorbidity burden observed in each study, it is unclear the extent to which less frequent dosing may have been a result of different patient profiles as compared to MagnetisMM-3. Other reasons may include sustained efficacy or patient preferences; however, our databases do not allow us to investigate these causes further.

Although the median follow-up time was still relatively short (<12 months), the results for TTNT/D and OS were similar to what was observed in MagnetisMM-3 and generally better than reported in other RW studies [ 14–16 ]. Of course, cross-study comparisons can be challenging based on differences in patient populations and data sources. Landmark analyses estimated that 60.7% and 70.0% of patients (from ALTITUDE-2 and ALTITUDE-1, respectively) were alive after 18 months. Additional studies with longer follow-up will be needed to confirm these findings and explore other outcomes such as progression-free survival and duration of response.

As the first analysis of RW treatment patterns for elranatamab, this study has several strengths. The use of two different datasets to analyze our research questions reinforced the robustness of the conclusions. Additionally, the flat-dose nature of elranatamab allowed for a comparison of RW versus on-label usage using vial orders regardless of patient weight. As a limitation, however, we acknowledge that there may have been individual patients who were included in both ALTITUDE-1 and ALTITUDE-2 (e.g., some patients on Medicare in the Komodo dataset from ALTITUDE-1 would be expected to also appear in the Medicare FFS dataset from ALTITUDE-2). Administrative claims data may come with inaccuracies due to provider coding practices. As also noted above, the data was not sufficiently sensitive to explore whether supportive medications such as tocilizumab were taken prophylactically or as a treatment for CRS. Similarly, acetaminophen and corticosteroids may represent home medications that patients self-administered, particularly in the outpatient setting, and may not be represented in the data. Given that over a quarter of RW elranatamab recipients in the US were previously BCMA-exposed, we would expect to find lower efficacy in our cohort with further follow-up as compared with MagnetisMM-3. However, we do note that a recent MagnetisMM-3 subgroup analysis of US patients reported both higher levels of optimal supportive care (e.g., antimicrobial prophylaxis and intravenous immunoglobulin) as well as improved PFS compared with the overall cohort [ 33 ]. Future analyses of these trends from the ALTITUDE-1 and ALTITUDE-2 studies with extended follow-up are planned.

Conclusion

In conclusion, our analyses provide valuable insights regarding the early integration of elranatamab into RW clinical practice in the US. Unsurprisingly, patients who initiated elranatamab were heavily pre-treated; this included a significant subset of patients with prior BCMA exposure, a factor known to reduce ORR and PFS with subsequent BCMA-directed BsAb therapy. Nevertheless, our analysis of outcomes suggests that the RW effectiveness of elranatamab is comparable to what was observed in the MagnetisMM-3 trial, with both the median time to next treatment or death and the median overall survival not reached. Landmark analyses estimated that between 60% and 70% of patients were alive at 18 months. We also found early evidence of elranatamab dose de-escalation compared with the USPI, a practice that requires more detailed investigations to better characterize. Updated analyses from ALTITUDE-1 and ALTITUDE-2 with larger sample sizes and longer follow-up are ongoing and will help answer these important questions.

Acknowledgments

The authors acknowledge the contributions of Brian Conroy, PhD to the statistical analysis.

Article highlights

Elranatamab is a BCMA-directed bispecific antibody approved in the United States (US) for relapsed/refractory multiple myeloma; real-world data remains limited following its recent approval. Using two US claims-based analyses (ALTITUDE-1, which used the Komodo Health Healthcare Map™ and ALTITUDE-2, which used Medicare fee-for-service data), this study assessed elranatamab treatment patterns and effectiveness. Adults with multiple myeloma initiating elranatamab after August 2023 ( N = 183 in ALTITUDE-1; N = 391 in ALTITUDE-2) were included. Elranatamab administration appeared less frequent than expected from on-label dosing (annualized ~27–28 vials vs 39 expected vias per label), with evidence of extended dosing intervals (i.e., biweekly dosing occurred earlier than anticipated and monthly dosing was observed). Neither median time-to-next-treatment or death (TTNT/D) nor median overall survival (OS) was reached; landmark OS at 18 months was 70.0% (ALTITUDE-1) and 60.7% (ALTITUDE-2). These results suggest that elranatamab is being adopted in heavily pre-treated patients with less frequent dosing observed and effectiveness broadly consistent with clinical trial experience.

Disclosure statement

R.B. reports consulting: Abbvie, Adaptive Biotech, Arcellx, BMS, Caribou Biosciences, Genentech, Gilead/Kite, GSK, Janssen, Karyopharm, Legend Biotech, Pfizer, Poseida Therapeutics, Sanofi, SparkCures; Research: Abbvie, BMS, Gilead/Kite, Janssen, Karyopharm, Novartis, Pack Health, Prothena, Sanofi. P.P., N.G., and E.B. were employees of and/or held stock options with Aetion at the time of study execution. W.P., C.C., and H.M. were employees of Clarify Health at the time of this study, which received funding from Pfizer. P.H., R.S., B.L. A.M., C.K., I.C., M.S., and M.D. are employees and stockholders of Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing and editorial support were provided by Aetion and funded by Pfizer.

Reviewer disclosures

A reviewer on this manuscript has disclosed “I receive lecture fee from Pfizer.” Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Ethical declaration

ALTITUDE-1 and ALTITUDE-2 were secondary research on previously collected de-identified data with no way to trace back or identify individuals. Given these considerations, each study received an institutional review board (IRB) exemption (WCG IRB, Cary, NC; Advarra IRB, Columbia, MD), and no informed consent was required.

Data availability statement

Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified patient data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.

References

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

1. Albagoush SA , Shumway C , Azevedo AM. StatPearls . Treasure Island, FL, USA : StatPearls Publishing ; 2024 . Available from: http://www.ncbi.nlm.nih.gov/books/NBK534764/

2. Myeloma - cancer stat facts . SEER ; 2025 . Available from: https://seer.cancer.gov/statfacts/html/mulmy.html

3. Kumar SK , Rajkumar SV , Dispenzieri A , et al . Improved survival in multiple myeloma and the impact of novel therapies . Blood . 2008 ; 111 ( 5 ): 2516 – 2520 . doi: 10.1182/blood-2007-10-116129 17975015 PMC2254544

4. Thorsteinsdottir S , Dickman PW , Landgren O , et al . Dramatically improved survival in multiple myeloma patients in the recent decade: results from a Swedish population-based study . Haematologica . 2018 ; 103 ( 9 ): e412 – e415 . doi: 10.3324/haematol.2017.183475 29567776 PMC6119139

5. Pinto V , Bergantim R , Caires HR , et al . Multiple myeloma: available therapies and causes of drug resistance . Cancers (Basel) . 2020 ; 12 ( 2 ): 407 . doi: 10.3390/cancers12020407 32050631 PMC7072128

6. Usmani S , Ahmadi T , Ng Y , et al . 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 . Oncologist . 2016 ; 21 ( 11 ): 1355 – 1361 . doi: 10.1634/theoncologist.2016-0104 27486203 PMC5189616

7. Rodriguez-Otero P , Usmani S , Cohen AD , et al . International myeloma working group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma . Lancet Oncol . 2024 ; 25 ( 5 ): e205 – e216 . doi: 10.1016/S1470-2045(24)00043-3 38697166

8. Gay F , Marchetti E , Bertuglia G . Multiple myeloma unpacked . Hematol Oncol . 2025 ; 43 ( S2 ): e70067 . doi: 10.1002/hon.70067 40517540 PMC12167648

9. Cowan AJ , Green DJ , Kwok M , et al . Diagnosis and management of multiple myeloma: a review . JAMA . 2022 ; 327 ( 5 ): 464 . doi: 10.1001/jama.2022.0003 35103762

10. Kumar SK , Callander NS , Adekola K , et al. Multiple myeloma, version 5.2026, NCCN clinical practice guidelines In oncology . J Natl Compr Canc Netw . 2026 ; 24 ( 1 ): e260001 . doi: 10.6004/jnccn.2026.0001 41671464

11. Lesokhin AM , Tomasson MH , Arnulf B , et al . Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results . Nat Med . 2023 ; 29 ( 9 ): 2259 – 2267 . doi: 10.1038/s41591-023-02528-9 37582952 PMC10504075

12. Tomasson MH , Iida S , Niesvizky R , et al . Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: update from the MagnetisMM-3 study . Hemasphere . 2024 ; 8 ( 7 ): e136 . doi: 10.1002/hem3.136 39055646 PMC11269363

13. Prince HM , Bahlis NJ , Rodriquez-Ortero P , et al . MagnetisMM-3: long-term update and efficacy and safety of less frequent dosing of elranatamab in patients with relapsed or refractory multiple myeloma . Blood . 2024 ; 144 ( Supplement 1 ): 4738 – 4738 . doi: 10.1182/blood-2024-208192

14. Portuguese A , Davis J , Raza S , et al . Real-world outcomes with elranatamab in multiple myeloma: a multi-center analysis from the United States multiple myeloma immunotherapy consortium . Blood . 2025 ; 146 ( Supplement 1 ): 136 . doi: 10.1182/blood-2025-136 41896552 PMC13039266 •• This study examines real-world outcomes associated with elranatamab.

15. Tomkins O , Giles H , Pratt G , et al . Elranatamab for relapsed/refractory multiple myeloma – multi-centre real-world outcomes from the United Kingdom . Blood . 2025 ; 146 ( Supplement 1 ): 4045 . doi: 10.1182/blood-2025-4045 •• This study examines real-world outcomes associated with elranatamab.

16. Popat R , Morjaria O , Tan C , et al . Real world efficacy and safety of elranatamab, a BCMA bispecific antibody for patients with relapsed and refractory multiple myeloma: an international myeloma working group immunotherapy database analysis . Blood . 2025 ; 146 ( Supplement 1 ): 4588 . doi: 10.1182/blood-2025-4588 •• This study examines real-world outcomes associated with elranatamab.

17. Shelbaya A , Kelton JM , Thompson J , et al . Real-world use and acceptance of biosimilar monoclonal antibodies of rituximab in oncology practice in the USA . Future Oncol . 2021 ; 17 ( 30 ): 3941 – 3950 . doi: 10.2217/fon-2021-0618 34259584

18. Hlavacek P , Schepart A , Silverstein AR , et al . Medicare characteristics, treatment, cost and survival in triple class exposed relapsed or refractory multiple myeloma . Future Oncol . 2023 ; 19 ( 11 ): 775 – 787 . doi: 10.2217/fon-2022-1018 37132520

19. FDA . ELREXFIO TM (elranatamab-bcmm) injection, for subcutaneous use initial U.S. approval: 2023 . 2023 . Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345s000lbl.pdf

20. Shah B , Sandin R , Liu Y , et al . Economic impact of elranatamab for treatment of patients with relapsed or refractory multiple myeloma . Clinicoecon Outcomes Res . 2025 ; 17 : 289 – 302 . doi: 10.2147/CEOR.S501404 40225701 PMC11992987

21. Costa LJ , LeBlanc TW , Tesch H , et al . Elranatamab efficacy in MagnetisMM-3 compared with real-world control arms in triple-class refractory multiple myeloma . Future Oncol . 2024 ; 20 ( 17 ): 1175 – 1189 . doi: 10.2217/fon-2023-0995 38415370 PMC11318743

22. Costa L , LeBlanc TW , Tesch H , et al . An updated indirect comparison of elranatamab versus a real-world external control arm in triple-class refractory multiple myeloma . BLCTT . 2025 ; 15 : 11 – 20 . doi: 10.2147/BLCTT.S516356 PMC12147782 40491859

23. Tsang C , O’Reilly JE , Carpenter L , et al . Comparison of outcomes with elranatamab and real world treatments in the UK for triple class exposed relapsed and refractory multiple myeloma . BMC Cancer . 2025 ; 25 ( 1 ): 1219 . doi: 10.1186/s12885-025-14624-9 40713551 PMC12297639

24. Mol I , Hu Y , LeBlanc TW , et al . A matching-adjusted indirect comparison of the efficacy of elranatamab versus physician’s choice of treatment in patients with triple-class exposed/refractory multiple myeloma . Curr Med Res Opin . 2024 ; 40 ( 2 ): 199 – 207 . doi: 10.1080/03007995.2023.2277850 38078866

25. Cirstea D , Kim EB , O’Neill S . Implementing the bispecific outpatient safe step-up (BOSS) program for elranatamab in ambulatory treatment of multiple myeloma . J Clin Onc . 2025 ; 43 ( 16 ): e19507 . doi: 10.1200/JCO.2025.43.16_suppl.e19507

26. Vianna P , Chakraborty R , Hossain S , et al . Safety and efficacy of elranatamab in patients with relapsed and/or refractory immunoglobulin light-chain amyloidosis . Blood . 2025 ; 146 ( 16 ): 1929 – 1935 . doi: 10.1182/blood.2025028383 40712156 PMC12757077

27. Vianna P , Chakraborty R , Hossain S , et al . Elranatamab in patients with relapsed and/or refractory light chain amyloidosis . Blood . 2024 ; 144 ( S1 ): 3304 . 10.1182/blood.2025028383 PMC12757077 40712156

28. Chakraborty R , Bhutani D , Maurer MS , et al . Safety and efficacy of teclistamab in systemic immunoglobulin light chain amyloidosis . Blood Cancer J . 2023 ; 13 ( 1 ): 172 . doi: 10.1038/s41408-023-00950-3 38012151 PMC10682473

29. Stalker M , Garfall A , Cohen A , et al . Safety and efficacy of teclistamab in patients with relapsed or refractory al amyloidosis . Eur J Haematol . 2025 ; 114 ( 3 ): 443 – 447 . doi: 10.1111/ejh.14348 39552142 PMC11798760

30. Forgeard N , Elessa D , Carpinteiro A , et al . Teclistamab in relapsed or refractory al amyloidosis: a multinational retrospective case series . Blood . 2024 ; 143 ( 8 ): 734 – 737 . doi: 10.1182/blood.2023022937 38096365

31. Scott SA , Roberts DL , Gupta VA , et al. Feasibility and safety of outpatient model for administration of bispecific antibodies: proceedings from an international myeloma society 21st annual meeting oral abstract . Clin Lymphoma Myeloma Leuk . 2025 ; 25 ( 9 ): 656 – 660 . doi: 10.1016/j.clml.2025.04.002 40345961

32. Chunara F , Lugo C , Osinski K , et al . Real-world treatment patterns for teclistamab and talquetamab in multiple myeloma (MM): experience from 609 patients . Blood Cancer J . 2025 ; 15 ( 1 ): 61 . doi: 10.1038/s41408-025-01254-4 40199861 PMC11979001

33. Nooka AK , Strouse CS , Larson SM , et al . Efficacy and safety of less frequent dosing with elranatamab (ELRA) in patients with relapsed or refractory multiple myeloma (RRMM): a US subgroup analysis from MagnetisMM-3 . J Clin Oncol . 2025 ; 43 ( 16_suppl ): 7549 . doi: 10.1200/JCO.2025.43.16_suppl.7549