An alternative fully human anti-BCMA CAR-T shows response for relapsed or refractory multiple myeloma with anti-BCMA CAR-T exposures previously

Abstract

Chimeric antigen receptor T (CAR-T) cells therapy has made remarkable progress in relapsed/refractory multiple myeloma (R/R MM) treatment. Unfortunately, patients still eventually experience disease progression or relapse even after receiving anti-BCMA CAR-T therapy. At present, there are limited data on available treatment options for patients who have progressed on anti-BCMA CAR-T therapy. In this study, we evaluated the safety and efficacy of fully human anti-BCMA CAR-T (HRC0202) in seven R/R MM patients who were previously exposed to anti-BCMA CAR-T therapy. Three patients received 6.0 × 10⁶ CAR⁺T cells/kg, one patient received 10.0 × 10⁶ CAR⁺T cells/kg and three patients received 15.0 × 10⁶ CAR⁺T cells/kg. Cytokine release syndrome (CRS) of grades 1-2 occurred in three patients (42.9%) and grade ≥3 in two patients (28.6%). Immune effector cell-associated neurotoxic syndrome (ICANS) was not observed in any of the patients. The best overall response rate (ORR) was 71.4% (5/7), with a stringent complete response/complete response (sCR/CR) achieved in three patients. The median progression-free survival (PFS) was 269 days, and median overall survival (OS) for all patients was not reached. The median peak concentration (C_max) of HRC0202 was 30117.70 (range, 6084.35-147415.10) copies/μg DNA. This study indicated that fully human anti-BCMA CAR-T (HRC0202) is a promising treatment for R/R MM patients who relapsed or refractory from prior anti-BCMA CAR-T infusion.

Fig. 1. Clinical overall response after HRC0202 infusion.

The bar chart shows the clinical overall response and follow-up of patients after HRC0202 infusion. Each bar represents an individual patient and corresponding number. The different colors represent different clinical response. sCR stringent complete response, CR complete response, VGPR very good partial response, PR partial response, MR minimal response, SD stable disease, PD progressive disease.

Fig. 2. Best response to the prior CAR-T and HRC0202.

(A) The chart shows different clinical response and their proportion to prior CAR-T and HRC0202. (B) The chart shows different patient and their best response to prior CAR-T and HRC0202. sCR stringent complete response, CR complete response, VGPR very good partial response, PR partial response, MR minimal response, NR no response, SD stable disease, PD progressive disease.

Fig. 3. Pharmacokinetics of HRC0202.

QPCR method was used to detect cell proliferation of HRC0202.

Fig. 4. Cytokine levels in each patient.

CBA and ELISA method were used to detect the cytokine levels before and after HRC0202 infusion. IFN-γ interferon-γ, IL-6 Interleukin-6, TNF Tumor necrosis factor, CRP C-reactive protein, IL-15 Interleukin-15.

Fig. 5. Comparison of pharmacokinetics between prior CAR-T and HRC0202.

The chart shows cell proliferation of prior CAR-T and HRC0202. Median C_max of prior CAR-T was 142970.50 (range, 206.60–733066.20) copies/μg DNA compared with median C_max of HRC0202 was 30117.70 (range, 6084.35–147415.10) copies/μg DNA (p = 0.136).