A B-cell maturation antigen (BCMA)/CD19 dual-targeting chimeric antigen receptor (CAR) T-cell therapy product — called KQ-2003 —showed early signs of efficacy in a small study of patients with relapsed or refractory multiple myeloma (R/R MM), including some with extramedullary disease (EMD).
“KQ-2003 showed early, deep, and durable response in patients with R/R MM,” said study author Hua Jiang, PhD, of Shanghai Fourth People’s Hospital at Tongji University in China, who presented the research findings at the 66th American Society of Hematology Annual Meeting and Exposition. “More importantly, it exerted promising and persistent efficacy in patients with EMD.”
The prospective, multicenter, phase I/IIa study investigating KQ-2003, a BCMA/CD19 dual-targeting CAR T-cell therapy product, enrolled 23 patients with R/R MM, 14 of whom had EMD (60.9%). All patients had been treated with one or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, anti-CD38, or a combination. Patients received lymphodepleting chemotherapy and then a single infusion of KQ-2003 at one of three dose levels.
Three patients received dose level 1 (DL1) of 1.0 x 106, 11 patients received DL2 at 2.0 x 106, and nine patients received DL3 at 3.0 x 106. Hematologic overall response (OR) was evaluable in 18 patients; 100% achieved very good partial response or better, with 90% and 100% achieving stringent complete response (sCR)/complete response (CR) at DL2 and DL3, respectively. Median time to sCR/CR was 2.7 months.
Measurable residual disease (MRD) negativity measured at 10-5 was achieved by 83% at three months and 82% at six months post-CAR T-cell infusion.
Dr. Jiang and colleagues also looked at the PET response rate in patients with EMD, which was 85.7%. About two-thirds (64.3%) of patients with EMD had a complete metabolic response, 21.4% had partial metabolic response, and 14.3% had stable metabolic disease.
Six-month progression-free survival (PFS) was 86.5%, and six-month overall survival (OS) was similar at 86.2%. There was no difference in PFS or OS for patients with or without EMD, Dr. Jiang said. Median PFS and OS were not reached.
Two on-study, therapy-related deaths occurred; four deaths occurred overall. Almost all patients experienced cytokine release syndrome (CRS; 90.0%), but the rate of grade 3 CRS was low at 5.0%. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in about one-fourth of patients (25.0%), with grade 3 ICANS occurring in 10.0% of patients. No dose-limiting toxicities occurred.
Among those patients who had follow-up data, detectable CAR-positive T cells were present in the peripheral blood for 66.7% at six months and 50.0% at 12 months.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Jiang H, Li L, Chen K, et al. A prospective investigator-initiated phase 1/2 study of BCMA/CD19 dual-targeting CAR T therapy in patients with relapsed/refractory multiple myeloma including those with extramedullary disease. Abstract 923. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 9, 2024; San Diego, California.
