Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Have Received a Prior BCMA-Targeted Therapy: Real World, Multi-Institutional Experience

Ferreri, Christopher J.; Hildebrandt, Michelle A.T.; Hashmi, Hamza; Shune, Leyla; McGuirk, Joseph P.; Sborov, Douglas W.; Wagner, Charlotte B; Kocoglu, Mehmet H.; Atrash, Shebli; Voorhees, Peter M.; Khouri, Jack; Dima, Danai; Afrough, Aimaz; Sannareddy, Aishwarya; Simmons, Gary; Davis, James A.; Kalariya, Nilesh; Peres, Lauren C.; Alsina, Melissa; Locke, Frederick L.; Sidana, Surbhi; Hansen, Doris K.; Patel, Krina; Puglianini, Omar Castaneda

doi:10.1182/blood-2022-164884

Cited by 20 publications

(18 citation statements)

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“…A recent study by Ferreri et al compared outcomes of real-world patients who received SOC ide-cel with or without prior BCMA-DT, reporting patients with prior BCMA-DT had lower ORR and PFS compared to those without. 12 There are some key differences between the population described in that study and ours. In our cohort and the KarMMa-1 cohort, the median number of prior LOT were similar (median of 6), while in that study, the BCMA-DTexposed group had a median of 9 prior LOT, which may have accounted for differences in outcomes.…”

Section: Discussionmentioning

confidence: 62%

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Efficacy and safety of idecabtagene vicleucel in patients with relapsed–refractory multiple myeloma not meeting the KarMMa‐1 trial eligibility criteria: A real‐world multicentre study

Dima,

Rashid,

Davis

et al. 2024

Br J Haematol

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SummaryIde‐cel received approval for relapsed–refractory multiple myeloma based on the results of the KarMMa‐1 trial. However, patients with significant comorbidities, aggressive disease and prior B‐cell maturation antigen‐directed therapy (BCMA‐DT) were excluded. This retrospective study evaluated real‐world outcomes of patients who did not meet the KarMMa‐1 eligibility criteria and were treated with standard of care (SOC) ide‐cel. A total of 69 patients from three US centres who did not meet the KarMMa‐1 criteria underwent ide‐cel infusion. The main reasons for trial ineligibility included baseline grade 3–4 cytopenia (39%), prior BCMA‐DT (26%), renal impairment (19%) and Eastern Cooperative Oncology Group performance status ≥2 (14.5%). Cytokine‐release syndrome occurred in 81% vs. 84%, and immune effector cell‐associated neurotoxicity syndrome occurred in 28% vs. 18% of SOC versus KarMMa‐1 patients, respectively. Early infection (≤8 weeks post‐infusion) and severe infection rates were 42% vs. 49% and 30% vs. 22% for the SOC versus KarMMa‐1 cohorts, respectively. Grade 3–4 cytopenias for SOC versus KarMMa‐1 cohorts were: neutropenia (87% vs. 89%), anaemia (51% vs. 60%) and thrombocytopenia (65% vs. 52%). Overall response rate was higher for the SOC cohort (93% vs. 73%), as was the complete response or better rate (48% vs. 33%). However, median progression‐free survival and overall survival were comparable between the two groups. Our findings support broadening the inclusion criteria of future trials evaluating ide‐cel.

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Section: Discussionmentioning

confidence: 62%

“…A recent study by Ferreri et al. compared outcomes of real‐world patients who received SOC ide‐cel with or without prior BCMA‐DT, reporting that patients with prior BCMA‐DT had lower ORR and PFS compared to those without 12 . There are some key differences between the population described in that study and ours.…”

Section: Discussionmentioning

confidence: 68%

Efficacy and safety of idecabtagene vicleucel in patients with relapsed–refractory multiple myeloma not meeting the KarMMa‐1 trial eligibility criteria: A real‐world multicentre study

Dima,

Rashid,

Davis

et al. 2024

Br J Haematol

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“…The ORR was 60% with a median PFS of 9.1 months, both substantially lower than observed in the BCMA-naïve cohort of CARTITUDE-1. 94 These data, in conjunction with real-world data of commercial ide-cel showing inferior outcomes in individuals previously treated with BCMA-directed therapies (median PFS of 3.2 [prior BCMA] v 9.0 [no prior BCMA] months; P = .0002), 95 suggest that sequencing of BCMA-directed therapies matters. Intriguingly, data from the MajesTEC-1 cohort C study, which enrolled participants (n = 40) with previous BCMA therapy (either ADC or CAR T), showed an ORR of 53% for teclistamab.…”

Section: Sequencingmentioning

confidence: 90%

Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapy in Multiple Myeloma: Moving Into the Future

Holstein

Grant

Wildes

2023

JCO

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Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective treatment options. However, the advent of chimeric antigen receptor (CAR) T-cell and T-cell redirecting bispecific antibody (BsAb) therapies has led to unprecedented response rates and durations of response in heavily relapsed/refractory (R/R) populations. Currently, two B-cell maturation antigen (BCMA)–directed CAR T-cell therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) as well as one BCMA/CD3 BsAb (teclistamab) have been approved for late-line (greater than four previous lines) R/R MM in the United States. The purpose of this review is to analyze the recent data for these approved therapies as well as provide an overview of other related CAR T-cell and BsAb therapies under development, including non–BCMA-targeting agents. We review efficacy and safety considerations, with particular focus on cytokine release syndrome, neurotoxicity, and infection risk. The relative merits and limitations of each class of therapy are discussed, as well as the areas of unmet need with respect to optimal sequencing and supportive care measures. We examine the factors that challenge equitable access to these novel therapies across minoritized racial, ethnic, and socioeconomic populations. Although it is evident that CAR T-cell and BsAb therapies will transform treatment paradigms in MM for years to come, significant work remains to identify the optimal utilization of these novel therapies and ensure equitable access.

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“…Teclistamab is administered intravenously once a week after initial loading and, similarly to CAR T-cell therapy, is approved for use in heavily pretreated patients. It is unclear whether prior exposure to or progression on one anti-BCMA therapy may affect the outcome of a subsequent yet different anti-BCMA therapy, with recent real-world data reporting lower responses in this context [ 226 , 227 ]. Enrollment in clinical trials of novel agents should always be encouraged based on availability and candidacy.…”

Section: How To Approach Therapy Selectionmentioning

confidence: 99%

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Dima

Ullah

Mazzoni

et al. 2023

Cancers

Self Cite

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Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

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Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Have Received a Prior BCMA-Targeted Therapy: Real World, Multi-Institutional Experience

Cited by 20 publications

References 0 publications

Efficacy and safety of idecabtagene vicleucel in patients with relapsed–refractory multiple myeloma not meeting the KarMMa‐1 trial eligibility criteria: A real‐world multicentre study

Efficacy and safety of idecabtagene vicleucel in patients with relapsed–refractory multiple myeloma not meeting the KarMMa‐1 trial eligibility criteria: A real‐world multicentre study

Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapy in Multiple Myeloma: Moving Into the Future

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

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