:: Ранняя смертность, связанная с дивидендной антителной терапией, в рамках RRMM: Иммунотерапевтическая база данных ММРГ, анализ реального мира.

Introduction

Multiple myeloma (MM) has seen tremendous progress over the past decade with improvements in outcomes. However, despite these improvements and development of novel therapies, early mortality (EM) remains an ongoing challenge. 1 EM is often defined as death within the first year of therapy initiation; however, some studies also use death within the first 3 or 6 months to define EM. The cause of EM is multifactorial and includes both early disease progression as well as disease morbidity and treatment-related toxicity. Infections remain an important cause of EM over time among patients with relapsed/refractory MM (RRMM), especially after therapy. 1 , 2 , 3 , 4

Bispecific antibodies (bsAbs) have emerged as important therapeutic agents in RRMM but are associated with distinctive toxicities. These include cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, cytopenias including neutropenias, profound hypogammaglobulinemia, and a high risk of infections, all of which may contribute to EM. The bsAbs teclistamab and elranatamab (B-cell maturation antigen [BCMA] × CD3) were associated with high overall response rates (ORR) of 63% and 61% in MajesTEC-1 and MagnetisMM-3, respectively. However, infection rates were high, with severe grade 3/4 infections occurring in ∼40% of patients. 5 , 6 After a median follow-up of ∼14 months for both studies, 68 (41%) and 55 deaths (45%) occurred in MajesTEC-1 and MagnetisMM-3, respectively, with progressive disease (25% and 30%) and infections (12% and 7%) as common causes of death. 5 , 7 Talquetamab, a G protein–coupled receptor class C group 5 member D–targeting bsAb, also has strong single-agent activity in the pivotal MonumenTAL-1 study, with ORR of 67% to 74%. 8 Pooled reports indicate infections in 59% to 73% of patients, with lower infection risk of grade ≥3 in 16% to 28%. 9 , 10 , 11 After a median follow-up ranging from 12.7 to 18.8 months for the different cohorts, deaths occurred in 23% to 39% of patients, mostly due to progressive disease; the number of infections that led to death was low at 0% to 2%. 11 However, the incidence and cause of EM as well as predictors of EM and potential mitigating factors in these pivotal trials are not readily identified.

Although retrospective series have reported real-world outcomes with bsAbs, 12 , 13 , 14 data specifically addressing EM and its rates, timing, and underlying causes remain scarce. Given the growing real-world use of these agents and their unique toxicity profiles, understanding the drivers of EM is crucial. This information will allow us to further optimize our treatment and supportive care strategies to minimize early deaths and improve overall outcomes. To better understand and address this gap, we conducted a multicenter, retrospective study using the International Myeloma Working Group (IMWG) immunotherapy database to characterize the incidence and causes of EM, defined as death within 12 months of therapy initiation, in patients treated with commercial bsAbs.

Methods

Study design and population

This was a multicenter retrospective study conducted through the IMWG immunotherapy database, as part of the IMWG Immunotherapy Committee. Eligible adults with RRMM who were aged ≥18 years and treated with at least 1 dose of teclistamab, elranatamab, or talquetamab either through commercial access or an expanded access program between 24 May 2022 and 16 June 2025 were included in the analysis. Linvoseltamab was not included because of insufficient follow-up due to very recent regulatory approvals. Patients treated as part of clinical trials were excluded. Treatment was delivered at academic centers from 7 countries. The final follow-up date was 28 August 2025. Institutional review board approvals and patient consents were obtained in accordance with institutional and international ethical standards. The study was conducted in compliance with the terms of the Declaration of Helsinki, and all methods were performed in accordance with the relevant guidelines and regulations.

Treatment and data collection

Drugs were administered per US Food and Drug Administration/European Medicines Agency (EMA)–approved labels and within institutional guidelines. Modifications to dosing schedules, prophylaxis, and supportive care were per institutional guidelines and based on individual physician discretion. Due to the original design of the study and database, high-risk cytogenetic abnormalities were defined as ≥1 of the following: 1q+, t(4;14), t(14;16), t(14;20), or del(17p). Hypogammaglobulinemia was defined as immunoglobulin G (IgG) level <400 mg/dL.

Clinical data were collected retrospectively from medical records and included baseline patient characteristics, myeloma and treatment details, specific adverse events (including infections and hypogammaglobulinemia), date of death, and the cause of death. For patients who received >1 commercial bsAb, only data pertaining to the last bsAb therapy received before the event were included in the analysis.

Outcomes and statistical analysis

The primary end point was EM, defined as all-cause mortality within 12 months of bsAb initiation. The secondary end point included cause(s) of death as reported by the institutional principal investigator or treating physician, progression-free survival (PFS; defined as the time from the start of bsAb until progression of disease or death from any cause), and response as assessed using IMWG consensus criteria. 15 For both EM and PFS outcomes, patients with follow-up of less than 12 months were censored at the time of last contact prior to the data analysis cutoff. The 12-month PFS and EM were estimated using the Kaplan-Meier method. Clinical and demographic characteristics of patients were summarized by frequencies (percentages) and medians with interquartile ranges (IQR) or range for categorical and continuous variables, respectively. Assessment of association between these characteristics and EM was conducted using univariate Cox proportional hazards model. All characteristics achieving P value <.1 in univariate analysis were further assessed for association in a multivariable Cox regression model. Variables with P value <.05 in multivariable Cox regression were considered statistically significant. All analyses were conducted using R version 4.3.0.

Results

Baseline characteristics

A total of 441 patients who received bsAb therapy across the different centers were included in the analysis. These included 234 patients who received teclistamab, 140 patients on talquetamab, and 67 patients on elranatamab. Among these patients, a total of 148 patients (34%) died within 12 months of therapy initiation (84/234 [36%] patients on teclistamab; 44/140 [31%] on talquetamab; 20/67 [30%] on elranatamab). Baseline characteristics of the overall patient population as well as patients in the EM and non-EM cohorts are listed in Table 1 . Patient and disease characteristics according to the specific immunotherapy received are listed in supplemental Tables 1 and 2 for the overall patient population and the EM cohort.

Among the 148 EM patients, the median age was 66 years (range, 36-92), with 19% of patients being aged ≥75 years. A total of 69 of 115 patients (60%) had high-risk cytogenetic abnormalities, and 46 of 102 (45%) had extramedullary disease (EMD). At the start of the immunotherapy, 33 of 73 patients (45%) had Eastern Cooperative Oncology Group performance status ≥2, and 25 of 140 patients (18%) had creatinine clearance of ≤30 mL per minute. The median time from diagnosis to first immunotherapy dose was 68 months (IQR, 39-99). The patients had heavily pretreated disease with a median of 6 prior lines of therapy (IQR, 4-8). The majority (88%) had triple-class refractory disease, and 56% of patients had penta-drug refractory disease. Among the 134 patients with pivotal bsAb trial eligibility assessments (MajesTEC-1, MagnetisMM-3, and MonumenTAL-1), 112 (84%) would have been ineligible for the respective pivotal trial. There were 84 patients (57%) who had BCMA-directed therapy before the current bsAb therapy: 48% in the teclistamab group, 77% in the talquetamab group, and 50% in the elranatamab group. IV immunoglobulin (IVIG) replacement was used in 20% of the EM cohort either before or after bsAb initiation ( Table 2 ).

Overall, a higher percentage of the EM subgroup had a higher Eastern Cooperative Oncology Group status, were heavily pretreated, had presence of EMD, and would not have met eligibility for the respective pivotal bsAb trials than the non-EM cohort. Additionally, there was less incidence of hypogammaglobulinemia and less utilization of IVIG in the EM subgroup.

ORR and survival

Among 401 response-evaluable patients, the ORR of the entire cohort was 66% (263/401; teclistamab 68%, talquetamab 69%, and elranatamab 55%). The ORR for 129-response evaluable patients in the EM group was 27% compared to 84% in the non-EM group, as illustrated in Figure 1 . In the EM group, 93 patients were primary refractory to their respective bsAb, with a median time to progression of 28 days (range, 3-196) from the start of therapy. The response rates for each immunotherapy for the full cohort and for the EM subgroup are in supplemental Figure 1 . The 6- and 12-month PFS of the entire cohort were 57.7% (95% confidence interval [CI], 53.2-62.7) and 44.9% (95% CI, 40.2-50.1), respectively ( supplemental Figure 2 A). The 6- and 12-month EM rates of the entire cohort were 75.2% (95% CI, 71.2-79.5) and 62.7% (95% CI, 58.0-67.7), respectively, as shown in supplemental Figure 3 A. The median follow-up was 17.1 months (95% CI, 15.9-19.0) for the total cohort. The median follow-up was 23.1 months (95% CI, 21.5-25.1), 15.6 months (95% CI, 14.3-17.0), and 8.6 months (95% CI, 6.9-10.9) for teclistamab, talquetamab, and elranatamab, respectively.

EM and causes of death

For the 148 patients in the EM group, the median time from the start of bsAb to death was 2.87 months (IQR, 1.38-6.85). Most deaths occurred within the first 6 months (n = 105; 24% of the total cohort; 71% of the EM cohort). More specifically, 80 EM patients (54% of the EM cohort) died within the first 3 months of bsAb initiation; an additional 25 deaths (17% of the EM cohort) occurred between 3 and 6 months ( Figure 2 ).

Progressive disease remained the leading cause of death (n = 107 [72%]), followed by infection (n = 19 [13%]). Five patients died of progressive disease in combination with either infection (n = 3), multiorgan failure (n = 1), or failure to thrive (n = 1). Regardless of the cause of death, 82% of all EM patients had evidence of active disease at the time of death. Among the patients who died within the first 3 months of therapy, 74% died of progressive disease, and 10% died of infection; 86% had evidence of active disease at the time of death ( Figure 2 ). For the 5 patients in the EM group who initially had a complete response or better to therapy, 2 patients died of progressive disease, 1 patient died due to other reasons with evidence of progressive disease, and 2 patients died from unknown causes. Among the 15 EM patients who achieved a very good partial response with bsAb, 7 died of progressive disease, 5 died of infection without evidence of progression, 1 patient died of comorbidities, 1 died of liver failure, and 1 died of unknown reasons, with evidence of progressive disease.

Among the patients who died from infection, documented infections included pneumonia, adenovirus viremia, Pseudomonas bacteremia with endocarditis, Klebsiella bacteremia, Enterococcus faecium bacteremia, cytomegalovirus hepatitis, respiratory viral infections (including COVID-19), and Methicillin-resistant Staphylococcus aureus pneumonia. Nine of 22 patients who had infection included as a cause of death had documented hypogammaglobulinemia; 5 of these were receiving IVIG replacement. Other causes of death included sudden death, failure to thrive, liver failure, colitis with multiorgan failure, intracranial hemorrhage in the setting of thrombocytopenia, and natural causes/comorbidities. Causes of death overtime are highlighted in Figure 2 . Further information on causes of death stratified by each immunotherapy regimen is shown in supplemental Table 3 .

Predictors of EM

With regard to predictors of mortality, univariate and multivariate analyses are shown in Table 3 . Variables with a P value <.1 on univariable analysis were included in the multivariable analysis. After backward stepwise regression with elimination of 1 variable at a time, the current multivariable model with 4 factors was determined. On multivariable analysis, baseline platelet count <50 × 10 9 /L before bsAb initiation (hazard ratio [HR], 1.93; 95% CI, 1.16-3.21; P = .02) was a risk factor for EM. Having at least a partial response to the bsAb of interest decreases the risk of EM (HR, 0.22; 95% CI, 0.12-0.40; P < .001). The presence of EMD (HR, 1.47; 95% CI, 0.97-2.22; P = .07) was a suggestive risk factor for EM, whereas use of IVIG replacement (HR, 0.58; 95% CI, 0.31-1.10; P = .08) was suggestively associated with a decreased risk of EM.

Discussion

In this large, multi-institutional, real-world analysis, EM occurred in approximately one-third of patients receiving bsAbs for RRMM. The majority of deaths occurred within the first 6 months and were primarily due to disease progression (72%), followed by infection (13%).

EM remains a challenge in the treatment of MM across all stages of disease, starting from diagnosis but particularly in late relapse. Numerous previous studies have shown that despite improvement in overall outcomes with novel therapies, EM remains high, and after some initial improvements in earlier decades, there appears to be a stagnation in the risk of EM in MM. 16 The estimate of EM in the newly diagnosed MM setting remains in the 10% to 20% range, 17 , 18 with higher rates estimated for older adults 19 and those with comorbidities. Previous studies in newly diagnosed MM have also demonstrated that the most common cause for EM was the MM disease itself. 17 In the relapsed/refractory setting, EM is less frequently reported as a dedicated end point but can often be inferred from attrition rates and early PFS data. In RRMM, EM is likely influenced by disease refractoriness, impaired immune response to infections, cumulative treatment toxicity, frailty, and declining performance status.

Specifically with regard to bsAb in RRMM, EM may be further complicated by unique toxicities such as cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and infections. Although specific information on EM is not available, the pivotal trials with bsAbs have reported some data on causes of death. In MajesTEC-1, after a median follow-up of 14.1 months, 68 (41%) deaths were reported, primarily due to progressive disease (n = 41 [25%]), and 20 (12%) deaths were due to infections, mostly COVID-19 related. 5 MajesTEC-1 was conducted in part during the COVID-19 pandemic, and no COVID-19 vaccines were available until 9 months after enrollment began. Similarly, in MagnetisMM-3, after a 14.7-month follow-up, 55 deaths (45%) occurred, including 37 (30%) due to progressive disease and 8 (7%) due to infection, which likely reflects improved infection prophylaxis and management in the post–COVID-19 era. 7 Lastly, in MonumenTAL-1, after a median follow-up of 18.8, 12.7, and 14.8 months in the weekly, biweekly, and prior T-cell redirection therapy cohorts, deaths occurred in 33.6%, 22.8%, and 39.2% of patients, respectively, primarily due to progressive disease (19.6%, 17.2%, and 37.3%). The number of deaths due to infection was low (2.1%, 1.4%, and 0%, respectively). 12

In both MajesTEC-1 and MagnetisMM-3, the early drop in the survival curves is clearly apparent and is in line with our findings in the real-world population. Our study complements and extends these clinical trial data by focusing on real-world patients who are typically underrepresented in trials. The observed EM rate of 34% is comparable to that seen in pivotal studies, confirming that progressive disease remains the dominant cause of early death. Notably, 82% of patients in our EM cohort had evidence of active disease at death, underscoring the urgent need for improved disease control strategies for RRMM. This is also reflected in the multivariable analysis, in which nonresponders had a significantly higher risk of EM. Significant thrombocytopenia (platelet count <50 × 10 9 /L) at bsAb initiation, as a reflection of significant MM marrow infiltration was also associated with EM, consistent with other studies, which have also shown this variable to be a proxy for poor outcomes among patients treated with teclistamab. 20 The early drop in survival curves in clinical trials and in our real-world study perhaps reflects the underlying mechanisms of primary resistance to bsAb therapy prevalent in RRMM. Although this resistance is likely multifactorial, the type and composition of preexisting T-cell repertoire, prior MM treatments, tumor burden, and other tumor compartment factors such as genomic pattern are all likely to influence outcomes. 21

Data in the real-world setting on EM associated with bsAb remain limited, with often a short duration of follow-up. A German multicenter cohort of 123 teclistamab recipients reported an ORR of 59.3% and a median PFS of 8.7. 22 Although grade ≥3 infections were reported in 26.8% of patients, the rates of fatal infection with or without progressive disease were unknown. A French study (median follow-up, 11.9 months) and a US teclistamab study (median follow-up, 3.8 months) both identified progressive disease as the leading cause of death. 23 , 24 Similarly, in a real-world study of 101 patients treated with elranatamab in an Intergroupe Francophone du Myélome (IFM) program, the ORR was 51.5%, the 1-year PFS rate was ≥34%, and 24% of the patients had grade ≥3 infection after a median follow-up of 15.5 months. 14 Details on EM and causes of death are not described in this study. Lastly, a German multicenter study of 138 patients treated with talquetamab reported an ORR of 65% and a median PFS of 6.4 months after a median follow-up of 8.2 months. 12 A total of 46 patients died during the follow-up period, with the majority of deaths due to progressive disease (n = 35 [76.1%]), similar to the findings in our study. Other causes of nonrelapse mortality (NRM) included sepsis (n = 3), other malignancies or related complications (n = 3), esophageal rupture (n = 1), and Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 1). 12

Although the majority of patients in the EM group died of progressive disease, infection was the second leading cause of death in our study at 13%, as well as in MajesTEC-1 (12%) and MagnestisMM-3 (7%). 5 , 7 These estimates are comparable to findings from a systematic review and meta-analysis of bsAbs for MM, which estimated NRM rates of 6.2%, primarily due to infections, particularly COVID-19, which was the leading cause of NRM. 25 Treatment-related T-cell activation, T-cell exhaustion, and depletion of certain T-cell populations, along with hypogammaglobulinemia and neutropenia, may contribute to the substantial infection risk associated with bsAb. Various bacterial, fungal, and viral infections, as well as opportunistic infections, have been reported with bsAbs in clinical trials and real-world studies. Guidelines on optimal bsAb use in MM have recommended various antimicrobial agents as prophylaxis for patients receiving bsAb and IVIG replacement for patients with immunoglobulin G levels <400 mg/dL. 26 , 27 In our study, use of IVIG had a suggestive association in decreasing the risk of EM. Other real-world studies have shown that the use of IVIG has resulted in significant reductions in rates of all grades and grade ≥3 infections. 28 , 29 , 30 Mohan et al 31 demonstrated that the use of primary IVIG prophylaxis was associated with improved infection-free survival and overall survival in patients treated with BCMA-directed bsAb. These findings suggest that primary IVIG prophylaxis may be an important mitigation strategy to improve outcomes in patients with RRMM treated with bsAb. 32

Limitations of our study include its retrospective nature, incomplete data for select variables, and reliance on investigator-reported causes of death. Further characterizations of or details related to deaths due to progressive disease were not available. Additionally, prophylactic and supportive care strategies, particularly for infection and hypogammaglobulinemia, were not standardized across participating centers. Nonetheless, this analysis represents, to our knowledge, the largest global data set specifically examining EM among real-world bsAb-treated patients with MM and provides crucial insights to inform both clinical trial design and frontline management strategies. Our study highlights the need for potential strategies to mitigate early progression and mortality, perhaps through debulking the disease before bsAb initiation, evaluating novel combination approaches with synergistic agents, or sequential bsAb therapy targeting different antigens. Incorporating genomic and biomarker-driven risk stratification may also enhance identification of patients at the highest risk of early treatment failure. Similarly, patients with early nonresponse to bsAbs or patients with low likelihood of delayed response conversion should be transitioned to a different therapy to lower the risk of myeloma-related or infectious mortality. 33 This study underscores the urgent need to evaluate bsAb therapy in earlier lines of therapy, before the development of EMD and multiagent refractoriness. Lastly, early and proactive prophylactic infection mitigation strategies, such as IVIG replacement, may need to be incorporated either at the time of bsAb initiation or even before, particularly among higher-risk patients, to potentially decrease the risk of infections.

Conclusion

EM remains a significant challenge in the management of real-world patients with RRMM on novel bsAb therapies, with most deaths occurring within 3 months of therapy initiation and driven predominantly by disease progression. Optimizing early disease control, integrating infection prevention, and refining patient selection are essential to improving survival outcomes in this high-risk population.

Conflict-of-interest disclosure: C.R.T. has received research funding from Janssen, Sanofi, and Takeda; and has served as a consultant for Janssen and Sanofi. S.U. has received research funding from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDx, and Takeda; and has served as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, EdoPharma, Genentech, Gilead, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, Seattle Genetics, SecuraBio, SkylineDx, Takeda, and TeneoBio. R. Parrondo serves on advisory boards for Sanofi, Janssen, AstraZeneca, and Bristol Myers Squibb; and has received research funding from the Bristol Myers Squibb Foundation, BeOne Medicines USA, and GlaxoSmithKline. S. Ailawadhi reports institutional research funding from GlaxoSmithKline, Bristol Myers Squibb, Pharmacyclics, Amgen, Sanofi, Janssen, Cellectar, Xencor, AbbVie, and Ascentage; and has served as a consultant for GlaxoSmithKline, Sanofi, Bristol Myers Squibb, Takeda, BeiGene, Regeneron, Pharmacyclics, Amgen, and Janssen. R. Popat has received research funding from Pfizer and GlaxoSmithKline; has served as a consultant for Roche and GlaxoSmithKline; has received honoraria from Janssen, AbbVie, Bristol Myers Squibb, Pfizer, and GlaxoSmithKline; and reports additional funding sources include Pfizer, GlaxoSmithKline, Myeloma UK, and the University College London Hospitals Biomedical Research Centre. R.H. has received consultancy or advisory fees from Janssen, Amgen, Celgene, AbbVie, Bristol Myers Squibb, Novartis, PharmaMar, and Takeda; honoraria from Janssen, Amgen, Celgene, Bristol Myers Squibb, PharmaMar, and Takeda; research funding from Janssen, Amgen, Celgene, Bristol Myers Squibb, Novartis, and Takeda; is a member of advisory boards for Bristol Myers Squibb, Takeda, Amgen, Oncopeptides, Sanofi, Janssen, and GlaxoSmithKline; and has received support for attending meetings and/or travel from Amgen, Celgene, Takeda, and Janssen. J.M. has received consultancy fees, honoraria, and conference sponsorship from AbbVie, Janssen, Novartis, and AstraZeneca. M.H. has received research funding from Janssen, Bristol Myers Squibb, and AstraZeneca. M.J. has served as a consultant for Janssen and Bristol Myers Squibb; has received research funding from Legend Biotech, Fate Therapeutics, and Janssen; has received honoraria from Legend Biotech, Bristol Myers Squibb, and Janssen; and is a member of advisory boards for Janssen. A.V. has received consulting fees and honoraria from Celgene/Bristol Myers Squibb, Janssen, Sanofi, Pfizer, Forus, and Amgen. E.K. has received honoraria from Janssen, GlaxoSmithKline, Sanofi, and Pfizer; and institutional research funding from Janssen, GlaxoSmithKline, and Pfizer. M.A.D. has received honoraria from Amgen, Takeda, Janssen, Bristol Myers Squibb, BeiGene, and Sanofi; and has served in consulting or advisory roles for Amgen, Janssen, Takeda, Bristol Myers Squibb, BeiGene, and Sanofi. J.M.-L. has received speaker honoraria from Adaptive Biotechnologies, Bristol Myers Squibb, Incyte, Sanofi, GlaxoSmithKline, Janssen, Novartis, Roche, Takeda, Pfizer, and Menarini; research grants to their institution from Bristol Myers Squibb, Janssen, GlaxoSmithKline, and Incyte; and advisory honoraria from AbbVie, Adaptive Biotechnologies, Janssen, Sanofi, Bristol Myers Squibb, Novartis, Incyte, Roche, Takeda, Pfizer, and Gilead. C.N. reports institutional research funding from Janssen and honoraria from Janssen and Pfizer. S.B. has served as a consultant for Bristol Myers Squibb, AstraZeneca, Kite/Arcellx, Janssen, AbbVie, and Pfizer; has received research funding from the Amyloid Foundation, Fate Therapeutics, Bristol Myers Squibb, and BeiGene; and has received honoraria from Adaptive Biotechnologies. L.J.C. has received research funding from Bristol Myers Squibb, Pfizer, Amgen, Janssen, Caribou Biosciences, Genentech, and AbbVie; has served in an advisory role for Bristol Myers Squibb, Pfizer, Sanofi, Amgen, Janssen, Caribou Biosciences, Genentech, and AbbVie; and has received honoraria from Bristol Myers Squibb, Pfizer, Sanofi, Janssen, Adaptive Biotechnologies, and BeOne. H.E. has served in consulting or advisory roles for Bristol Myers Squibb/Celgene, Janssen, Amgen, Takeda, Sanofi, GlaxoSmithKline, and Novartis; received research funding from Bristol Myers Squibb, Janssen, Amgen, GlaxoSmithKline, and Sanofi; and received honoraria from Bristol Myers Squibb, Janssen, Amgen, Takeda, Sanofi, GlaxoSmithKline, and Novartis. T.S. has received travel reimbursement from Janssen. J.M.W. has received consultancy fees from Janssen, Sanofi, Takeda, Pfizer, Oncopeptides, Menarini-Stemline, SkylineDx, AbbVie, Amgen, and GlaxoSmithKline. C.R. has received consultancy fees from Janssen and Takeda. R.B. has served as a consultant for AbbVie, Adaptive Biotechnologies, Bristol Myers Squibb, Caribou Biosciences, Genentech/Roche, Gilead/Kite, GlaxoSmithKline, Karyopharm, Legend Biotech, Janssen, Pfizer, Poseida Therapeutics, Sanofi Pasteur, and SparkCures; and has received research funding from AbbVie, Bristol Myers Squibb, Janssen, Novartis, Pack Health, Prothena, and Sanofi. W.J.C. has received research funding from GlaxoSmithKline, Sanofi, Janssen, and Antangene; and honoraria from Pfizer, Sanofi, Bristol Myers Squibb, Antangene, Janssen, and GlaxoSmithKline. Y.L. has received consultancy fees from Janssen, Legend Biotech, Celgene, Sanofi, Bristol Myers Squibb, Regeneron, and Genentech; research funding from Janssen, Celgene, and Bristol Myers Squibb; and serves on advisory boards for NexImmune, Caribou Biosciences, and Pfizer. T.M. has received research funding from Sanofi, Janssen, Amgen, and Bristol Myers Squibb and has served as a consultant for GlaxoSmithKline, Roche, and Pfizer. H.M. has received research funding from Janssen and Pfizer; and honoraria and advisory board fees from Janssen, GlaxoSmithKline, Sanofi, Pfizer, Takeda, and AbbVie. The remaining authors declare no competing financial interests.

Acknowledgements

The authors acknowledge the International Myeloma Foundation for its support of this project and the International Myeloma Working Group immunotherapy database. Data were provided by each participating site.

C.R.T. and S.U. are supported by the Memorial Sloan Kettering National Institutes of Health (NIH)/National Cancer Institute (NCI) Cancer Center Support grant (P30 CA008748). R.P. is supported by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre.

Authorship

Contribution: H.M., C.R.T., and T.M. were responsible for designing and writing the protocol and interpreting results; A.D. conducted statistical analysis; H.M. and C.R.T. wrote the manuscript draft; and all authors reviewed and/or edited the manuscript, had full access to study data, and take final responsibility for the decision to submit for publication.

Footnotes

The data that support the findings of this study are available from the International Myeloma Working Group (IMWG) immunotherapy database, but restrictions apply to the availability of these data, which were used under for this study and therefore are not publicly available. Data are however available from the corresponding author, Carlyn Rose Tan ( tanc4@mskcc.org ), upon reasonable request and with permission of IMWG immunotherapy database.

The full-text version of this article contains a data supplement.

Supplementary Material

Supplemental Tables and Figures

References

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