|The following article features coverage from the 61st American Society of Hematology Annual Meeting and Exposition. Click here to read more of Hematology Advisor’s conference coverage.|
Results of long-term follow-up of a clinical trial featuring a chimeric antigen receptor T-cell (CAR-T) therapy expressing 2 antibodies against BCMA showed that approximately three-quarters of patients achieved a complete response (CR). The findings from this study were reported during the 61st American Society of Hematology (ASH) Annual Meeting and Exposition held in Orlando, Florida.1
The high unmet need in patients with relapsed/refractory multiple myeloma is evidenced by reports of median overall survival (OS) times of less than 1 year for those who have progressive disease following 3 or more prior lines of therapy.
BCMA makes an attractive therapeutic target because it is expressed at significantly higher levels on myeloma cells compared with normal B cells.
Previous reports from the ongoing, first-in-human, phase 1 LEGEND-2 clinical trial (ClinicalTrials.gov Identifier: NCT03090659) designed to evaluate the safety and efficacy of a CAR-T cell therapy (LCAR-B38M) expressing 2 antibodies against BCMA in adult patients with relapsed/refractory multiple myeloma revealed promising results, including a high response rate and a manageable safety profile.2
Baseline characteristics of patients enrolled in this study included a median age of 54 years, a median of 3 prior lines of therapy, a median time from initial multiple myeloma diagnosis of 4 years, and prior treatment with both a proteasome inhibitor and an immunomodulatory drug in 60% of patients.
At a median follow-up of 25 months, 57 patients had received on-study treatment with LCAR-B38M at the main clinical trial site. The median dose of LCAR-B38M was 0.5×106 CAR-T cells/kg.
Regarding the safety of LCAR-B38M, 90% of patients experienced cytokine release syndrome (CRS), although, with the exception of 4 grade 3 events, all of these events were classified as grade 1/2.
CRS had a median onset of 9 days following infusion of LCAR-B38M, and a median duration of 9 days. Tocilizumab was administered to 46% of patients experiencing CRS. Grade 1 neurotoxicity occurred in 1 patient.
Grade 3/4 leukopenia, thrombocytopenia, and anemia occurred in 30%, 23%, and 18% of patients, respectively.
The overall response rate was 88%, with rates of CR, minimal disease negative (MRD)-CR, very good partial responses (VGPR), and partial response (PR) of 74%, 68%, 4%, and 11%, respectively.
At a median follow-up of 25 months, the median duration of response was 27 months and 29.1 months in the overall study population and in patients achieving a CR, respectively.
Median progression-free survival was 28.2 months and 3.2 months for patients achieving a CR compared with those who did not, respectively. While median overall survival (OS) for patients who did not achieve a CR was 7.5 months, at 25-month follow-up, OS has not yet been reached in the subgroup of patients who saw a CR.
In her concluding remarks, Dr Bai-Yan Wang of the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, the presenting study author, noted that a phase 2 confirmatory study of LCAR-B38M has been initiated in China (ClinicalTrials.gov Identifier: NCT03758417), and she also mentioned the ongoing phase 1b/2 study of the same anti-BCMA CAR-T therapy being conducted in the US (CARTITUDE; ClinicalTrials.gov Identifier: NCT03548207).
- Wang B-Y, Zhao W-H, Liu J, et al. Long-term follow-up of a phase 1, first-in-human open-label study of LCAR-B38M, a structurally differentiated chimeric antigen receptor T (CAR-T) cell therapy targeting B-cell maturation antigen (BCMA), in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 579.
- Zhao WH, Liu J, Wang BY, et al. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018;11:141.
This article originally appeared on Cancer Therapy Advisor