Belantamab Mafodotin Shows Real-World Efficacy in Pretreated R/R Myeloma

"In our analysis, [belantamab mafodotin] was associated with notable efficacy in patients with heavily pretreated disease who had progressed through multiple [lines of therapy] including prior BCMA-directed therapy," according to the study authors.

Treatment with belantamab mafodotin-blmf (Blenrep) demonstrated notable efficacy and appeared safe among patients with heavily pretreated relapsed/refractory multiple myeloma, although the presence of extramedullary disease (EMD) was associated with worse outcomes, according to findings from a real-world study.¹

Across all patients, the median progression-free survival (PFS) was 5 months (95% CI, 1-20), and the median OS was 12 months (95% CI, 3-28). Additionally, the median PFS was 2 months (95% CI, 1-5) for patients with EMD compared with 10 months (95% CI, 1-32) in those without EMD (P = .003). In patients with and without EMD, respectively, the median OS was 5 months (95% CI, 2-15) vs 22 months (95% CI, 5-not reached [NR]; P = .000).

In patients with high-risk and standard-risk disease, treatment yielded a median PFS of 5 months (95% CI, 1-12) and 4 months (95% CI, 1-32), respectively (P = .570). The median OS was 9 months (95% CI, 2-22) and 17 months (95% CI, 3-NR) in each respective group (P = .043).

Among those with an ECOG performance status of 2 to 4 and those with a performance status of 0 to 1, respectively, the median PFS was 5 months (95% CI, 1-16) vs 5 months (95% CI, 1-14; P = .818). Additionally, the median OS was 3 months (95% CI, 2-21) and 16 months (95% CI, 5-NR) in each respective group.

The rates of partial responses (PRs), very good PRs (VGPRs), and complete responses (CRs), respectively, were 17%, 7%, and 15% in all patients compared with 17%, 0%, and 7% in those with EMD. The respective rates were 20%, 4%, and 13% in patients with high-risk cytogenetics as well as 11%, 5%, and 8% in those with penta-refractory disease.

Multivariate analysis showed that having high-risk cytogenetics conferred significantly worse OS (HR, 2.49; 95% CI, 1.36-4.55; P = .0032). Additionally, having EMD was associated with significantly worse OS (HR, 3.05; 95% CI, 1.71-5.45; P = .0002) and PFS (HR, 1.97; 95% CI, 1.11-3.50; P = .0205). An ECOG performance status of 2 to 4 also conferred significantly worse OS (HR, 1.90; 95% CI, 1.05-3.42; P = .0329).

“In our analysis, [belantamab mafodotin] was associated with notable efficacy in patients with heavily pretreated disease who had progressed through multiple [lines of therapy] including prior BCMA-directed therapy,” Rachel Dileo, DO, from the Division of Hematology and Cellular Therapy at Allegheny Health Network, wrote with study coauthors.¹ “[Belantamab mafodotin] appeared safe in this real-world heavily pretreated [relapsed/refractory multiple myeloma] population, where majority of patients did not meet the eligibility criteria for the DREAMM-2 trial [NCT03525678] and had high-risk disease features.²”

Investigators aimed to evaluate the real-world efficacy and safety outcomes of belantamab mafodotin in patients with relapsed/refractory multiple myeloma who may be considered ineligible for enrollment on a clinical trial. The analysis focused on outcomes among those with dose delays and reductions.

Study authors collected data from 5 US academic institutions on 81 patients who received belantamab mafodotin under a commercial label or as part of an expanded program from October 2019 to September 2023. All patients in the analysis had 3 months of follow up or longer at the time of data cutoff.

Investigators assessed responses per International Myeloma Working Group (IMWG) response criteria. Evaluation of PFS and OS involved the use of Kaplan-Meier analysis. Adverse effects (AEs) were determined via CTCAE v5.0 criteria.

The median age was 67 years (range, 37-85), and most patients were male (63%) and non-Hispanic White (77%). Most patients had Revised International Staging System stage III disease (46%), an ECOG performance status of 0 or 1 (63%), and double-refractory disease (95%). The median number of prior lines of therapy was 5 (range, 2-10), and 80% of patents had 4 or more lines of prior therapy.

Regarding ocular toxicity, any-grade and grade 3 or higher keratopathy affected 69% and 30% of patients, respectively. The median time to onset was 21 days (range, 15-98), and the median time to resolution was 42 days (range, 21-180). A visual decline to less than 20/50 best corrected visual acuity (BCVA) occurred in 32%, and a decline to less than 20/200 BCVA was reported in 21%.

Grade 3 anemia, neutropenia, thrombocytopenia, and infections occurred in 28%, 20%, 31%, and 17% of patients, respectively.

“Ocular toxicities remained a major therapeutic challenge, highlighting the need for future investigations to optimize the dosing and frequency of administration for better tolerability,” the study authors concluded.

Investigators presented these findings in a poster session at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).

References

1. Dileo R, Mewawalla P, Patrus G, et al. Safety and efficacy of belantamab mafadotin in patients with relapsed/refractory multiple myeloma: a real-world experience. Blood. 2024;144(suppl 1):4742. doi:10.1182/blood-2024-206059
2. A study to investigate the efficacy and safety of two doses of GSK2857916 in participants with multiple myeloma who have failed prior treatment with an anti-CD38 antibody. ClinicalTrials.gov. Updated October 23, 2024. Accessed January 27, 2025. https://tinyurl.com/2a75da87