ASH 2025 Early MRD negativity with in vivo CAR T-cell therapy in R/R MM

MedNet.nl: The initial results of the Australian phase 1 inMMyCAR trial of KLN-1010 in patients with relapsed or refractory multiple myeloma (R/R MM) have been published in a late-breaking abstract. The early responses to this intravenous in vivo CAR T-cell therapy were promising: after 1 month, all patients had an MRD-negative response.

KLN-1010 is an intravenous CAR T-cell therapy, administered via a modified lentivirus, which selectively converts T cells into fully human anti-BCMA CAR T cells. The results of the first three patients treated with KLN-1010 are now available.

These three heavily pretreated patients with R/R MM had received three to four prior therapies and were at high cytogenetic risk. Two of them were double refractory to both a proteasome inhibitor and immune-modulating anti-CD38 therapy. The time between informed consent and administration of KLN-1010 was 13 to 18 days.

During infusion and CAR T-cell expansion, all three patients experienced mild to moderate infusion-related reactions (IRRs) and grade 2 cytokine release syndrome. Immune-related neurotoxicity was not observed.

T-cell proliferation occurred without prior lymphodepletion. Peak values were reached between day 13 and day 18 for absolute lymphocyte count (2.3–43.1×10⁹/L) and on day 15 for CAR-positive CD3+ cells (72%). CAR T cells were detectable in peripheral blood and bone marrow for up to 3 months after infusion, with a predominantly memory phenotype.

All three patients achieved MRD negativity after 1 month. In the patient with the longest follow-up, the response deepened after 3 months to a very good partial response (VGPR). To date, all three patients remain in response, with no signs of disease progression. The study is continuing with further dose escalation and longer follow-up.

Harrison S, Joy Ho P, Lim S-L, et al. Minimal residual disease (MRD)-negative outcomes following a novel, in vivo gene therapy generating anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells in patients with relapsed and refractory multiple myeloma (RRMM): Preliminary results from inMMyCAR, the first-in-human phase 1 study of KLN-1010. ASH Annual Meeting & Exhibition, abstract LBA-1.

This article was originally published in Dutch on MedNet.nl