LCAR-B38M CAR-T Therapy Yields High Complete Response Rate and Survival Time

Conference Correspondent 

In patients with relapsed/refractory (R/R) multiple myeloma, a high overall response rate and deep responses were achieved with low chimeric antigen receptor (CAR) T-cell doses.

LCAR-B38M is a structurally differentiated CAR T-cell therapy containing a 4-1BB co-stimulatory domain and 2 B-cell maturation antigen (BCMA)-targeting single-domain antibodies. In the phase 1 LEGEND-2 trial, involving 74 patients with R/R multiple myeloma enrolled at 4 hospitals in China, the drug displayed a safety profile consistent with other safety reports of BCMA-targeting CAR T-cell therapy.

As of the July 31, 2019, cutoff date, at a median follow-up of 25 months, 57 patients had been infused with LCAR-B38M at one of the sites, the Second Affiliated Hospital of Xi’an Jiaotong University. Bai-Yan Wang, MD, PhD, presented long-term follow-up data on safety and efficacy from this cohort.

Patients had a median age of 54 years, a median time from initial diagnosis of 4 years, and a median of 3 prior lines of therapy. Prior proteasome inhibitors were used in 68% of patients, while 86% had received treatment with immunomodulatory drugs and 60% had received both.

After leukapheresis, patients received 300 mg/m2 of cyclophosphamide as preconditioning therapy, followed by infusion of CAR+ T-cells on day 1, day 3, and day 7 at a median dose of 0.5 × 106 cells/kg. The first efficacy assessment was made on day 30.

The overall response rate was 88%, with complete responses achieved by 42 patients (74%), 68% of whom became minimal residual disease (MRD)-negative, which has become established as a marker of a drug’s efficacy. Very good partial responses were seen in 2 patients (4%), and partial responses were seen in 6 patients (11%).

Median duration of response was 27 months in all patients, and was 29.1 months in patients who achieved complete responses; the median time to initial response was approximately 1 month. There was no relationship between best response and baseline BCMA expression level or weight-adjusted CAR+ cells infused.

Median progression-free survival (PFS) was 19.9 months in all treated patients, rising to 28.2 months in MRD-negative complete responders. In patients without complete response, PFS was 3.2 months.

Longest PFS was 39 months in 1 patient who had received 5 prior lines of treatment. As of September 2019, this patient remains disease-free, with no detectable transgenic CAR in circulation, and complete resolution of his extramedullary lesions. “No maintenance treatment was given after his LCAR-B38M infusion,” she noted. “This patient is now tumor-free and treatment-free.”

Median overall survival was 36.1 months in total, and has not yet been reached in patients who achieved complete response.

“Patients who reached complete response in this study had a long survival benefit,” she said.

Almost all patients experienced some adverse event, including pyrexia (91%), cytokine release syndrome (90%), thrombocytopenia (49%), and leukopenia (47%). Grade ≥3 adverse events were observed in 65% of patients, including leukopenia (30%), thrombocytopenia (23%), and increased aspartate aminotransferase (21%). Cytokine release syndrome was mostly grade 1 (47%) and grade 2 (35%), with only 4 patients (7%) developing grade 3 toxicity (none of higher grades) and 1 patient experiencing mild neurotoxicity. All but one such event resolved.

“This study provides evidence that LCAR B38M is a highly effective therapy for relapsed/refractory myeloma, regardless of baseline BCMA expression,” Dr Wang reported. “LCAR-B38M displayed a manageable safety profile consistent with its known mechanism of action and, with a median follow-up of 25 months, demonstrated a high overall response rate and deep and durable responses.”

Three studies are ongoing in the United States, using an identical construct: a phase 1b/2 study, (CARTITUDE-1, with early results reported at ASH), a phase 2 multicohort study (CARTITUDE-2) evaluating different populations of patients with multiple myeloma, and a phase 3 study (CARTITUDE-4) evaluating standard-of-care treatments versus JNJ-4528 in patients with multiple myeloma who have received 1 to 3 prior lines of therapy and are refractory to lenalidomide. A phase 2 confirmatory study, CARTIFAN-1, is ongoing in China at 7 sites.


Wang BY, et al. ASH Abstract 579.

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