Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma

Rodríguez‐Otero, Paula; Ailawadhi, Sikander; Arnulf, Bertrand; Patel, Krina; Cavo, Michèle; Nooka, Ajay K.; Manier, Salomon; Callander, Natalie S.; Costa, Luciano J.; Vij, Ravi; Bahlis, Nizar J.; Moreau, Philippe; Solomon, Scott R.; Delforge, Michel; Berdeja, Jesús G.; Truppel-Hartmann, Anna; Yang, Zhihong; Favre-Kontula, Linda; Wang, Fan; Piasecki, Julia; Cook, Mark; Giralt, Sergío

doi:10.1056/nejmoa2213614

Cited by 158 publications

(71 citation statements)

References 26 publications

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“…In a phase 1b/2 open‐label study, a single infusion of ciltacabtagene autoleucel (cilta‐cel) resulted in deep and durable responses in heavily pretreated patients with MM 24 . In yet another study, treatment with idecabtagene vicleucel (ide‐cel) CAR‐T therapy led to increased PFS and improved responses in patients with TCE RRMM who received two to four prior standard regimens 25 …”

Section: Discussionmentioning

confidence: 99%

“…In a phase 1b/2open-label study, a single infusion of ciltacabtagene autoleucel (ciltacel) resulted in deep and durable responses in heavily pretreated patients with MM 24. In yet another study, treatment with idecabtagene vicleucel (ide-cel) CAR-T therapy led to increased PFS and improved responses in patients with TCE RRMM who received two to four prior standard regimens 25. 5 | CONCLUSIONSDespite developments in therapeutic strategies for MM, patients still face a very poor prognosis after their disease becomes refractory to multiple treatments.…”

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confidence: 99%

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Survival outcomes for patients with multiple myeloma in France: A retrospective cohort study using the Système National des Données de Santé national healthcare database

Leleu

Gorsh

Bessou

et al. 2023

European J of Haematology

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Objective: Evaluate the overall survival (OS) of patients with multiple myeloma (MM) at different treatment stages in France. Methods: This retrospective observational cohort study used data from the French National Health Insurance database to study patients with MM (diagnosis 2013-2019). Patient outcomes included OS (all-cause mortality), time-to-next treatment (TTNT), and duration of therapy (DoT) from initial diagnosis, the start of different lines of therapy (LOTs), triple-class exposure (TCE), and subsequent treatment following TCE. The Kaplan-Meier method analyzed "time-to-event" data. Results: From diagnosis, death rates increased from 1% at 1 month to 24% at 2 years; median OS was 63.8 months (N = 14 309). Median OS from the start of LOTs declined from 61.0 months (LOT1) to 14.8 months (LOT4). Median OS from TCE start was 14.7 months. There was a large variation in TTNT within LOTs (e.g., LOT1: bortezomib + lenalidomide: TTNT = 26.4 months, OS = 61.7 months; lenalidomide: TTNT = 20.0 months, OS = 39.6 months); DoT was similar for LOT1 and LOT2, then progressively declined at LOT4. Patients with stem cell transplant, younger age, and less comorbidity had better survival outcomes. Conclusions: Patients with MM face a poor prognosis after relapse to multiple LOTs and TCE, demonstrating a worsening of survival outcomes. Access to novel therapies may improve outcomes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Survival outcomes for patients with multiple myeloma in France: A retrospective cohort study using the Système National des Données de Santé national healthcare database

Leleu

Gorsh

Bessou

et al. 2023

European J of Haematology

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“…KarMMa-3 is a phase III study that compared the efficacy of ide-cel to standard regimens in 386 RRMM patients who had received 2–4 prior therapies including an IMiD, PI and DARA (triple class exposed) and who had refractory disease to their last regimen. Of these, 66% had triple-class-refractory and 95% DARA-refractory disease [ 141 ]. ORR (71% vs. 42%, p < 0.001), ≥CR rate (39% vs. 5, p < 0.001) and median PFS (13.3 vs. 4.4 months, p < 0.001) were all superior for the ide-cel arm.…”

Section: Available Therapeutic Modalitiesmentioning

confidence: 99%

“…ORR (71% vs. 42%, p < 0.001), ≥CR rate (39% vs. 5, p < 0.001) and median PFS (13.3 vs. 4.4 months, p < 0.001) were all superior for the ide-cel arm. OS data are not yet mature [ 141 ].…”

Section: Available Therapeutic Modalitiesmentioning

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

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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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“…In the phase 2 KarMMa (NCT03361748) study, treatment with ide-cel led to an unprecedented overall response rate (ORR) of 73% and a median overall survival of 24.8 months in a heavily pretreated patient population with relapsed/refractory multiple myeloma (RRMM) [ 14 ]. The randomized phase 3 KarMMa-3 trial (NCT03651128) recently reported improved progression-free survival (PFS) for ide-cel in RRMM compared to standard of care [ 15 ]. The efficacy of cilta-cel is being currently assessed in two first-line phase 3 trials, for patients with newly diagnosed MM, unfit or unwilling to receive treatment consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) (CARTITUDE-5, NCT04923893), and as alternative to ASCT for first line consolidation (CARTITUDE-6, NCT05257083).…”

Section: Introductionmentioning

confidence: 99%

Real-life experiences with CAR T-cell therapy with idecabtagene vicleucel (ide-cel) for triple-class exposed relapsed/refractory multiple myeloma patients

et al. 2023

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Background Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory multiple myeloma (RRMM), leading to unprecedented responses in this patient population. Idecabtagene vicleucel (ide-cel) has been recently approved for treatment of triple-class exposed RRMM. We report real-life experiences with the commercial use of ide-cel in RRMM patients. Methods We performed a retrospective analysis of the first 16 triple-class exposed RRMM patients treated with ide-cel at a single academic center. We assessed toxicities, response to treatment, CAR T expansion and soluble BCMA (sBCMA) levels. Results We identified 16 consecutive RRMM patients treated with ide-cel between 06–10/2022. Median age was 69 years, 6 (38%) patients had high-risk cytogenetics, 3 (19%) R-ISS stage III, and 5 (31%) extramedullary disease. Median number of previous treatment lines was 6 (3–12). Manufacturing success rate was 88% (6% required second lymphapheresis, 6% received an out-of-specification product). At 3 months, the overall response rate (ORR) was 69% (44% sCR, 6% CR, 19% VGPR). Cytokine release syndrome (CRS) occurred in 15 (94%) patients (88% G1, 6% G2), immune effector-cell associated neurotoxicity syndrome (ICANS) in 1 (6% G1), febrile neutropenia in 11 (69%), and infections in 5 (31%). Prolonged hematologic toxicity occurred in 4/16 (25%) patients. Other non-hematological toxicities were elevated hepatic enzymes (38%), colitis (6%, G3) and DIC (6%, G2). Responses were more frequent in patients with higher CAR T expansion (100% vs 38%), and lack of decrease or plateau of sBCMA levels was typically observed in non-responders. Conclusions We report one of the first cohorts of RRMM treated with commercial ide-cel. The ORR was 69% and safety profile was manageable, but prolonged hematologic toxicity still represents a major challenge. Responses correlated with in vivo CAR T cell expansion, underlining the need of further research to optimize CAR T expansion.

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Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma

Cited by 158 publications

References 26 publications

Survival outcomes for patients with multiple myeloma in France: A retrospective cohort study using the Système National des Données de Santé national healthcare database

Survival outcomes for patients with multiple myeloma in France: A retrospective cohort study using the Système National des Données de Santé national healthcare database

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

Real-life experiences with CAR T-cell therapy with idecabtagene vicleucel (ide-cel) for triple-class exposed relapsed/refractory multiple myeloma patients

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