BCMA-targeted CAR T therapy yields 100% response in relapsed/refractory MM

All 29 patients with progressive myeloma included in the phase 1b/2 CARTITUDE-1 trial attained objective responses with JNJ-4528, including complete responses in two-thirds of the patients [1]. All patients evaluable for minimal residual disease (MRD) were MRD-negative.

The study, presented by Dr Deepu Madduri (Mount Sinai Medical Center, USA), examined the investigational CAR T-cell therapy JNJ-4528. These CAR T-cells bind to 2 different epitopes on the B-cell maturation antigen (BCMA). BCMA is almost always overexpressed in multiple myeloma.

The study population was heavily pre-treated, had a median age of 60 years, a median disease duration of 6 years, as well as a median of 5 prior lines of therapy. All of the patients had received 3 standard therapies for myeloma (i.e. protease inhibitor, immunomodulatory agent, and CD38 inhibitor), and all but 2 of the patients had triple-refractory disease. Additionally, 25 of 29 patients had undergone autologous transplantation.

Safety was the primary outcome of the current study, although efficacy was also included in the phase 2 outcomes. Like all CAR T therapies, adverse events were significant. Haematologic toxicity was common, including neutropenia in 93% of patients (all grade ≥3), anaemia in 86% (55% grade ≥3), thrombocytopenia in 86% (69% grade ≥3), leukopenia in 52% (52% grade ≥3), and lymphopenia in 45% (31% grade ≥3). The most common non-haematologic adverse events were increased liver enzymes (AST and ALT), diarrhoea, and upper respiratory tract infection, occurring in 25-30% of patients. Grade ≥3 non-haematologic toxicity was infrequent, consisting of 2 cases of increased AST and 1 each of increased ALT and diarrhoea. Out of 29 patients, 27 developed cytokine release syndrome, which reached grade 3 severity in 1 patient and was associated with 1 death. Immune effector cell-associated neurotoxicity syndrome occurred in 3 patients, including grade ≥3 in 1 patient. Dr Madduri said there were no unexpected treatment-related adverse events, and toxicity in general was manageable.

"We observed early and deep responses in patients, and 27 of 29 patients remained progression free at 6 months of follow-up," Dr Madduri said. "Safety and efficacy results are consistent with a previous study conducted in China. The phase 2 portion of the study is fully enrolled, and phase 2 and 3 studies have been initiated." The treatment just received breakthrough therapy designation from the FDA, she added.

1. Madduri D, et al. Abstract 577, ASH 2019, 7-10 December, Orlando, USA.

Posted on 5 March, 202028 March, 2024