2021 IMW Big Coffee Commentary | Professor Chen Wenming's interpretation of ide-cel treatment of RRMM

Patients with relapsed and refractory multiple myeloma (RRMM) with a history of exposure to immunomodulators, proteasome inhibitors (PI) and anti-CD38 monoclonal antibodies have a poor prognosis after subsequent treatment
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The KarMMa study confirmed that the CAR-T cell therapy idecabtagene vicleucel (ide-cel, bb2121) targeting BCMA can achieve deep and lasting remission in RRMM patients exposed to the three drugs.
The latest results have been announced at the 2021 IMW meeting.
Tong specially invited Professor Chen Wenming from the Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, to comment on this
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Research topic A BCMA-targeted CAR-T cell therapy idecabtagene vicleucel (ide-cel, bb2121) for the treatment of patients with relapsed and refractory multiple myeloma (RRMM): the latest results from the KarMMa study The research method has previously received ≥3 lines of treatment (Including immunomodulators, PI, and anti-CD38 monoclonal antibodies) and patients who are refractory to the last treatment plan are eligible for enrollment
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After 3 days of lymphocyte depletion chemotherapy (cyclophosphamide 300mg/m2 + fludarabine 30mg/m2), the patient received 150-450×106 CAR-T cell therapy
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The primary study endpoint is the overall response rate (ORR), the key secondary endpoint is the complete response (CR) rate (CR+strictly complete response [sCR]), and other secondary endpoints include duration of response (DOR) and progression-free survival (PFS), overall survival (OS) and safety
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The results of the study were 128 patients who received ide-cel treatment
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The median age of the patient was 61 years old, and the median number of previous treatments was 6 (range: 3-16), of which 84% were triple refractory and 26% were quintuple refractory (lenalidomide, Pomalidomide, bortezomib, carfilzomib and daretuzumab)
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At the end of the statistics (December 21, 2020), the median follow-up time for surviving patients was 24.
8 months
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Overall, the ORR was 73% (94/128), the CR rate was 33%, the median DOR and PFS were 10.
9 months and 8.
6 months, respectively, the median OS was 24.
8 months, and the estimated 24-month OS rate Is 51%
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Among patients achieving ≥CR, the median DOR was 21.
5 months, and the median PFS was 22.
4 months
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Patients who received higher dose treatment had better curative effect.
The ORR of the 450×106 CAR-T cell dose group was 81%, the CR rate was 39%, the median DOR was 11.
3 months, and the median PFS was 12.
2 months; in In patients who achieved ≥CR at this dose, the median DOR was not achieved
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All subgroups of patients had remission, including patients with refractory subgroups (eg high tumor burden [ORR of 71%], extramedullary disease [ORR of 70%], and R-ISS stage III disease [ORR of 48%])
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The most common toxic events of any grade were neutropenia (91%) and cytokine release syndrome (CRS; 84%)
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CRS was mainly grade 1/2, 5 patients (4%) were grade 3, 1 patient was grade 4, and 1 patient was grade 5 (Grade 4 and grade 5 CRS occurred in patients in the 300×106 dose group)
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Twenty-three patients (18%) developed neurotoxicity (assessed by the investigator), of which 5 patients (4%) were grade 3 and there were no events ≥ grade 4
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67 and 3 patients with CRS and neurotoxicity were treated with tocilizumab, and 19 and 10 patients were treated with steroids
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Research conclusions The latest results of the KarMMa study still prove that ide-cel can achieve long-lasting and deep relief in RRMM patients who have been exposed to multi-line treatment and three drugs
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The efficacy and safety data are consistent with previous research results
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Professor Chen Wenming commented that the three major classes of drugs targeting BCMA (including antibody-drug conjugates [ADC], bispecific antibodies, and CAR-T cells) are the hotspots in the field of MM research in recent years, especially those targeting BCMA CAR-T cell therapy is particularly prominent, not only has good efficacy but also high safety
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The KarMMa study confirmed that the CAR-T cell therapy ide-cel targeting BCAM has a good effect in the treatment of RRMM, and therefore it was approved for marketing in the United States
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The IMW meeting reported the latest results of the KarMMa study, which further confirmed that ide-cel can provide lasting and deep remission for RRMM patients with previous multi-line treatment, multi-drug exposure, and even drug resistance, and its efficacy and safety are obtained.
Further confirmation
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In fact, China is also at the forefront of the world in the study of CAR-T cells targeting BCMA.
It is expected that CAR-T cells targeting BCMA developed in China will be approved for marketing as soon as possible, benefiting Chinese patients
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Professor Chen Wenming, Chief Physician, Professor, Doctor of Medicine, and Doctoral Supervisor, Director of the Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Director of Beijing Multiple Myeloma Medical Research Center, Director of the Department of Hematology, Capital Medical University, Consultant of the International Myeloma Working Group and China Multiple Myeloma Working Group Expert Committee Member of the Hematology Professional Committee of China Medical Education Association Member of the Standing Committee of the Hematology Branch of the Chinese Integrative Medicine Association Member of the Standing Committee of the Hematology Branch of the Chinese Society of Geriatrics Member of the Transplantation Group, Member of the Hematological Oncology Branch of the Chinese Anti-Cancer Association Reference Materials: Larry D.
Anderson, Jr, et al.
2021 IMW.