New CAR-T therapy for multiple myeloma with 60% remission rate
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The New CAR-T therapy for multiple myeloma with 60% remission rate, which is worth looking forward to!
Multiple myeloma is the second largest hematological malignancy after lymphoma and is more common than leukemia. It occurs mostly in the elderly.
Recently, the FDA granted the title of Regenerative Medicine Advanced Therapy (RMAT) for allogeneic CAR-T cell therapy as a potential therapy for patients with relapsed/refractory multiple myeloma.
▌MM’s “resistance curse”
Multiple myeloma (MM) is the second largest hematological malignancy after non-Hodgkin’s lymphoma and is more common than leukemia. It is characterized by abnormal proliferation of bone marrow plasma cells, which occurs mostly in old age. As aging process accelerates in many countries, the incidence of multiple myeloma will continue to increase.
In recent years, although great progress has been made in chemotherapy, proteasome inhibitors, immunomodulators, and CD38 targeting antibodies, almost all patients will eventually develop resistance and relapse.
Moreover, with the increase in the number of treatments, the degree, duration, and survival time of the patient’s response are gradually decreasing.
For patients with relapsed or refractory multiple myeloma with limited clinical treatment, the prognosis is poor, and the response rate is only 20%-30%, the survival rate is low, and better innovative therapies are needed.
▌CAR-T therapy targeting BCMA
B cell maturation antigen (BCMA) is widely present on the surface of MM cells and has become a popular therapeutic target for MM and other hematological malignancies in recent years.
At present, there are more than 20 types of immunotherapies developed for BCMA, which are mainly divided into: chimeric antigen receptor T cell therapy (CAR-T), bispecific antibody (BsAb), antibody drug conjugate (ADC).
In the past two years, the ADC drug Blenrep, the CAR-T therapy Abecma, and the anti-cancer peptide-conjugated drug Melflufen have been approved, and they have also injected “cardiotonic agents” into the treatment of multiple myeloma.
The research therapies targeting BCMA include AMG 420, TNB-383B, Idecabbtagene vicellel, P-BCMA-101 and so on. In the future, this disease will get rid of the “curse” of drug resistance.
▌Total remission rate is 60%, clinical trials are worth looking forward to!
At the ASH annual meeting in 2020, some data from the ongoing UNIVERSAL Phase 1 clinical trial was announced.
The trial included 35 patients who had failed at least three-line treatment, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies in adult patients with relapsed/refractory MM who had to be resistant to the last-line treatment. The primary endpoints are dose limiting toxicity (DLT) and safety and tolerability.
These patients have been pretreated with lymphocyte depletion (LD), and then infused with CAR-T cells in 4 different drug doses (DL). The experiment is the ALLO-715 dose escalation plan: 40*106, 160*106 , 320*106 and 480*106 CAR-T.
Among them, there are several lymphocyte elimination programs: FCA, FCA+, CA (F refers to fludarabine, C refers to cyclophosphamide, and A refers to ALLO-715).
Among the 31 patients whose curative effect can be evaluated, the median age is 65 years old. Nearly half of the patients (48%) are at high-risk cytogenetic risk, and 23% have extramedullary disease manifestations.
The results show that:
The total remission rate of the CAR-T therapy group in the 320*106 dose group was 60%; in addition, complete remission and good partial remission were observed in each patient.
The total remission rate of patients in the CAR-T therapy group in the 160*106 dose group was 50%, while no response was observed in the lowest dose group.
It is worth noting that at the time of the data cutoff, 80% of patients who responded to treatment were still in remission. It means that the drug is expected to maintain the patient’s continuous remission, and higher doses of CAR-T therapy may have better anti-cancer activity in patients with relapsed/refractory MM.
It is hoped that the drug will complete clinical trials as soon as possible to help patients with multiple myeloma relieve the plight of drug resistance and benefit more patients with relapses.
(source:internet, reference only)
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