Analysis of Factors Affecting Forimtamig Efficacy in RRMM Patients

For a study, researchers aimed to assess the efficacy and safety of forimtamig in high-risk r/r MM patients. Eligible patients had r/r MM and had received at least one prior line of therapy (LOT), with refractoriness to both a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD). Patients received forimtamig at target doses ranging from 0.018 to 10 mg, administered either intravenously (IV) or subcutaneously (SC) following prior administration of two-step doses.

Efficacy was assessed in various subgroups, including those aged ≥65 years, with more than four prior LOT, triple-class and penta-drug refractory disease, prior BCMA-targeted therapy, high-risk cytogenetics (del(17p), t(4;14), t(14;16)), 1q21 gain (irrespective of other high-risk aberrations), ISS disease Stage III at baseline, high tumor burden ((>median sBCMA at baseline), and the presence of soft tissue plasmacytoma (bone-based and extramedullary). The primary endpoint was the objective response rate (ORR) assessed per the International Myeloma Working Group (IMWG) criteria.

The result demonstrated that 20 patients in the efficacy-evaluable population received forimtamig in the dose escalation study. The median age was 63 years, and the median time from diagnosis to enrollment was 6.2 years (range: 0.4–30.7). ORR across all dose levels was 66.7% (very good partial response or better: 54.2%), with a median response duration of 12.2 months (range: 0.03–20.8), and 61.3% responders with ongoing responses at cut-off. High ORRs were observed across all risk groups. 

The result demonstrated that 20 patients in the efficacy-evaluable population received forimtamig in the dose escalation study. The median age was 63 years, and the median time from diagnosis to enrollment was 6.2 years (range: 0.4–30.7). ORR across all dose levels was 66.7% (very good partial response or better: 54.2%), with a median response duration of 12.2 months (range: 0.03–20.8), and 61.3% responders with ongoing responses at cut-off. High ORRs were observed across all risk groups. 

Patients aged ≥65 years (n=52) and those with >4 lines of therapy (n=49) had ORRs of 71.2% and 63.3%, respectively. Among patients with high-risk cytogenetics (n=33), the ORR was 63.4%, while those with 1q21 gain (n=15) had an ORR of 86.7%. In patients with triple-class (n=81) and penta-drug (n=45) refractory disease, ORRs were 60.5% and 57.8%, respectively. 

About 29 patients had received prior BCMA-targeted therapy (n=19 with antibody-drug conjugates [ADCs], n=5 with BsAbs, and n=5 with CAR T-cells, including n=3 with ADCs and BsAbs or CAR T-cells). ORRs were 51.2% in all patients, 47.4% in ADC, 42.9% in BsAb, and 66.7% in CAR T-cell. ORRs in patients with ISS disease Stage III (n=24) and extramedullary disease (n=28), factors known to be of prognostic relevance for T-cell-directed therapy, were 70.8% and 50.0%, respectively.

Levels of sBCMA, a potential novel biomarker for tumor load and disease monitoring, above (n=54) and below (n=55) the median at baseline (327 ng/ml) were associated with ORRs of 55.6% and 80.0%, respectively.

The study demonstrated clinical efficacy and safety in high-risk r/r MM patients, warranting further evaluation for long-term treatment benefit.

Source: https://imsannual2023.eventscribe.net/fsPopup.asp?PresentationID=1302339&mode=presInfo 

Clinical Trial: https://clinicaltrials.gov/study/NCT04557150

Harrison SJ. Efficacy of forimtamig, a GPRC5DxCD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): analysis of patient- and disease-related factors associated with responses.Melbourne, Australia: Peter MacCallum Cancer Centre