As of the October 14, 2021 data cutoff, 48 patients were enrolled with 43 patients evaluable for safety and efficacy. Patients were refractory to their last line of myeloma therapy, had a median of five prior lines of therapy, and 42% were penta-refractory meaning the disease has ultimately become nonresponsive to other approved therapies. Five patients became ineligible for treatment due to rapidly progressing disease. The median time from enrollment to the start of therapy was five days.
The Phase 1 UNIVERSAL trial evaluated lymphodepletion followed by ALLO-715 at one of four dose levels (DL1=40M cells, DL2=160M cells, DL3=320M cells, DL4 = 480M cells) and two LD regimens (FCA: fludarabine, cyclophosphamide and ALLO-647 or CA: cyclophosphamide and ALLO-647 only). The updated presentation primarily focuses on the optimized DL3 cell dose and FCA lymphodepletion.
The higher CAR T cell doses were associated with an increased response rate and greater AlloCAR T cell expansion. In the DL3 cohort which was selected for cohort expansion, the overall response rate (ORR) increased from 60% reported at ASH 2020 to 71% with 46% of patients achieving a very good partial response (VGPR) or better (VGPR+) up from 40%. VGPR+ is defined as a stringent complete response (sCR), complete response (CR) or VGPR. Of the patients who achieved VGPR+, 92% were Minimal Residual Disease (MRD) negative.
As of the data cutoff, the overall median follow-up for efficacy was 3.8 months. The median duration of response is 8.3 months, with nine patients remaining in ongoing response at the time of the data cut-off. The longest ongoing response after cell infusion is 12 months. Results showed that soluble BCMA levels were 10 times lower in responders at Day 28, suggesting soluble BCMA suppression is associated with response.
Of the 43 patients evaluable for safety, there was no graft-versus-host-disease (GvHD). Grade 1 and 2 cytokine release syndrome (CRS) was reported in 23 patients (53%) and was manageable with standard therapies. In this heavily pre-treated patient population, infection occurred in 54% of patients, which included three Grade 5 infections, two of which were previously reported. Grade 3+ neutropenia occurred in 70% of patients. Six patients (14%) experienced adverse events of low-grade neurotoxicity, which was reversible. Use of tocilizumab and steroids was infrequent (23% and 14%, respectively).
