Research in context
Evidence before this study
We searched PubMed on Dec 18, 2020, with no date restriction, using the keywords “relapsed or refractory”, “myeloma”, “B-cell maturation antigen”, “chimeric antigen receptor T (CAR T)”, and “clinical trial”. From the seven articles identified, one reported results with a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, idecabtagene vicleucel, which showed deep and durable responses in patients with relapsed or refractory multiple myeloma. Two studies reported results with LCAR-B38M, a novel CAR construct that consists of two BCMA single-domain antibodies designed to confer avidity. LEGEND-2 is an investigator-initiated, first-in-human phase 1 study in China that evaluated LCAR-B38M CAR T-cell therapy for relapsed or refractory multiple myeloma in patients previously treated with a proteasome inhibitor, immunomodulatory drug, or both. Following treatment with LCAR-B38M, patients had deep, durable responses with a manageable safety profile.
Added value of this study
In this phase 1b/2 study of citla-cel (using a CAR construct identical to LCAR-B38M, a single infusion of cilta-cel led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma, with a manageable safety profile at the recommended phase 2 dose. The overall response rate was 97%, with most patients achieving their first response within a month of infusion. Cilta-cel showed unprecedented clinical activity in this challenging-to-treat population compared with other novel anti-myeloma treatments.
Implications of all the available evidence
Cilta-cel might be a viable treatment option for patients with relapsed or refractory multiple myeloma, with the highest overall response rate achieved to date in this heavily pretreated population who received a previous proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody, including those who are triple-class refractory or penta-drug refractory. Cilta-cel is under further investigation in other populations of patients with multiple myeloma in earlier line settings.