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Objective:To explore the efficacy and safety of anti-B cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) for the retreatment of relapsed and refractory multiple myeloma (RRMM).Methods:The clinical data of 10 RRMM patients who received anti-BCMA CAR-T therapy for the second time (CART2) in Henan Province Hospital of Traditional Chinese Medicine due to failure or recurrence after their first anti-BCMA CAR-T (CART1) therapy from January 2017 to June 2021 were retrospectively analyzed. The treatment, efficacy and adverse events of patients receiving CART2 therapy were summarized; and the objective response rate (ORR), median duration of response (DOR) and incidence of adverse reactions were compared between CART1 and CART2.Results:Among 10 patients, 8 were males and 2 were females, with a median age of 57 years (41-70 years). Patients' 3-month ORR after CART1 therapy was 90%, and the median DOR was 16.0 months (3.0-27.0 months). CART2 used human-derived anti-BCMA CAR-T to treat 6 cases and mouse-derived anti-BCMA CAR-T to treat 4 cases. The 3-month ORR of patients receiving CART2 therapy was 40%, and the median DOR was 8.5 months (3.0-11.0 months). Among 9 patients who received mouse-derived anti-BCMA CAR-T in CART1 therapy, 4 of them received the same product again and none of them showed curative effect. Among 6 patients retreated with human-derived anti-BCMA CAR-T, 4 patients (66.7%) of them achieved partial remission (PR) or better. During CART1 therapy, 10 patients developed grade 1-2 cytokine release syndrome (CRS), and 7 patients developed different degrees of decrease in leukocyte, neutrophil absolute count (ANC) and platelet. Among patients who achieved effective outcomes after receiving CART2 therapy, 4 patients of them developed grade 1-2 CRS, and different degrees of decrease in white blood cell, ANC and thrombocytopenia. Immune effector cell-related neurotoxicity syndrome was not observed.Conclusions:Anti-BCMA CAR-T is effective and safe to retreat RRMM. The ORR and DOR of patients receiving CART2 therapy are lower than those of patients receiving CART1 therapy. CRS and cytopenia are common adverse reactions.
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When chimeric antigen receptor T cells (CAR-T) failed to treat relapsed and refractory B-cell malignancies, some researchers try to improve the efficacy by enhancing the function of CAR-T. It is a new hotspot of drug development and clinical research, and significant achievements have been made in this area recently. Multi-targeted CAR-T, lenalidomide, decitabine, programmed death 1 inhibitor and ibrutinib can all enhance the function of CAR-T. This article reviews the recent progress of enhancing the function of CAR-T in relapsed and refractory B-cell malignancies.
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Objective:To explore the clinical effect of lenalidomide combined with anti-B-cell maturation antigen chimeric antigen receptor T cell (anti-BCMA CAR-T) in the treatment of relapsed/refractory multiple myeloma (RRMM).Methods:The clinical data of a patient with RRMM who underwent lenalidomide combined with anti-BCMA CAR-T therapy in Henan Province Hospital of Traditional Chinese Medicine in January 2020 were analyzed. Clinical manifestations, diagnosis and treatment were also analyzed, and the related literature was reviewed.Results:The patient was a 51-year-old man who was diagnosed as IgD-λ multiple myeloma (MM) in October 2015. The patient achieved remission after 10 courses of chemotherapy regimens including immunomodulators and proteasome inhibitors, followed by autologous hematopoietic stem cell transplantation. MM relapsed after 14 months of transplantation. His disease continued to progress after multiple chemotherapy regimens and mouse or human-derived anti-BCMA CAR-T therapy. After a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, the patient took lenalidomide on day 1 and was infused human-derived anti-BCMA CAR-T cells on the next day. Grade 3 cytokine releasing syndrome (CRS) appeared after infusion, and was resolved after symptomatic treatment. Very good partial response (VGPR) was achieved on day 14 after anti-BCMA CAR-T treatment. VGPR had been maintained for more than 3 months by press time.Conclusion:Lenalidomide combined with anti-BCMA CAR-T therapy is feasible and effective in the treatment of RRMM.