Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma.

Abstract

LBA3001 Background: Chimeric antigen receptor engineered T cell (CAR-T) is a novel immunotherapeutic approach for cancer treatment and has been clinically validated in the treatment of acute lymphoblastic leukemia (ALL). Here we report an encouraging breakthrough of treating multiple myeloma (MM) using a CAR-T designated LCAR-B38M CAR-T, which targets principally BCMA. Methods: A single arm clinical trial was conducted to assess safety and efficacy of this approach. A total of 19 patients with refractory/relapsed multiple myeloma were included in the trial. The median number of infused cells was 4.7 (0.6 ~ 7.0) × 10e6/ kg. The median follow-up times was 208 (62 ~ 321) days. Results: Among the 19 patients who completed the infusion, 7 patients were monitored for a period of more than 6 months. Six out of the 7 achieved complete remission (CR) and minimal residual disease (MRD)-negative status. The 12 patients who were followed up for less than 6 months met near CR criteria of modified EBMT criteria for various degrees of positive immunofixation. All these effects were observed with a progressive decrease of M-protein and thus expected to eventually meet CR criteria. In the most recent follow-up examination, all 18 survived patients were determined to be free of myeloma-related biochemical and hematologic abnormalities. One of the most common adverse event of CAR-T therapy is acute cytokine release syndrome (CRS). This was observed in 14 (74%) patients who received treatment. Among these 14 patients there were 9 cases of grade 1, 2 cases of grade 2, 1 case of grade 3, and 1 case of grade 4 patient who recovered after treatments. Conclusions: A 100% objective response rate (ORR) to LCAR-B38M CAR-T cells was observed in refractory/relapsed myeloma patients. 18 out of 19 (95%) patients reached CR or near CR status without a single event of relapse in a median follow-up of 6 months. The majority (14) of the patients experienced mild or manageable CRS, and the rest (5) were even free of diagnosable CRS. Based on the encouraging safety and efficacy outcomes, we believe that our LCAR-B38M CAR-T cell therapy is an innovative and highly effective treatment for multiple myeloma.

T-cells “à la CAR-T(e)” – Genetically engineering T-cell response against cancer

“…BCMA is a normal plasma cells marker, falls in to the near-ideal antigen for multiple myeloma with no evidence of expression on the normal non-hematological tissue [144]. Latest multi-center BCMA-CAR trials results indicate a relatively safe profile (although cytokine release syndrome -CRS and transient neurotoxicity were observed) with an overall response rate over 90% [145,146]. Other antigens currently being targeted to treat hematological malignancies include CD20 for NHL, CD138 for MM [144], CD33 [147], CD123 for AML [148,149] and CD7 for certain leukemias and lymphomas [150].…”

Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives

“…In addition, Fan et al presented the results of the LEGEND-2 study, which included 22 patients infused with the anti-BCMA LCAR-B38 M CAR product. An ORR of 100% was achieved with 63% of patients going into MRD-negative CR by flow cytometry [25]. These promising results are to be confirmed in larger numbers and with extended follow-up.…”

“…Indeed, severe CRS occurred in only 14% of the patients included in the LEGEND-2 trial [25]. In another study (CRB-401), Grade 1-2 CRS was reported in 73% treated patients.…”

Chimeric Antigen Receptor T Cells: Extending Translation from Liquid to Solid Tumors

“…Encouragingly, the CAR principle was also successfully used to target other antigens in liquid tumor patients, such as anti-CD20 CAR T cells in refractory advanced DLBCL and refractory B-cell non-Hodgkin lymphoma patients (ClinicalTrials.gov study NCT01735604), 31,32 anti-CD22 CAR T cells to treat B-ALL patients, 33 anti-CD138 CAR T cells in multiple myeloma patients (ClinicalTrials.gov study NCT01886976), 34 and in two early-phase clinical trials targeting BCMA in multiple myeloma in the United States (ClinicalTrials.gov study NCT02658929) 35,36 and China. 37,38 Noteworthy, the FDA granted Breakthrough Designation for anti-BCMA CAR T-cell therapy in multiple myeloma. 39 CAR T-cell therapies are also being tested in various solid tumors, but this setting may present additional challenges not faced in the treatment of liquid tumors.…”