Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP)

Abstract

Introduction Belantamab mafodotin (BM) is a new anti-BCMA antibody–drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). Methods We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). Results Thirty-three patients were included with a median of 70 years of age (range, 46–79 years). Median time from diagnosis was 71 months (range, 10–858 months). Median prior lines was 5 (range, 3–8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1–16 doses), with a median follow-up of 11 months (6–15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92–5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10–0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107–740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient’s decision (3%). Conclusions BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.

Single‐agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Final analysis of the DREAMM‐2 trial

“…Overall, the results of DREAMM‐2 have meaningfully informed ongoing and future studies of belamaf: patients who respond demonstrate rapid responses that are sustained for long durations. These results have translated into clinical practice, where similar real‐world results have been reported 14,19,38 …”

“…In this real‐world study, patients who were refractory to anti‐CD38 mAbs had a median OS of 8.6 months, with OS ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory agent and a PI, to 5.6 months for penta‐refractory patients 6 . Additional real‐world studies have demonstrated similar findings, consistent with the clinical trial setting 15–19 …”

“…6 Additional real-world studies have demonstrated similar findings, consistent with the clinical trial setting. [15][16][17][18][19] Despite having similar ORR and PFS, the shorter DoR reported here for the 3.4 mg/kg cohort may be due to tolerability issues requiring more frequent dose modifications. AEs such as thrombocytopenia and ocular events were frequently managed with dose delays that allowed for event resolution before recommencing treatment.…”

“…These results have translated into clinical practice, where similar real-world results have been reported. 14,19,38 In conclusion, single-agent belamaf at 2.5 or 3.4 mg/kg Q3W resulted in rapid, durable, and clinically meaningful responses with a manageable safety profile in patients who have received three or more prior therapies for RRMM, including an anti-CD38 mAb, a PI, and an immunomodulatory agent. This is a patient population with otherwise poor prognosis and limited treatment options.…”

Explosive Disease Progression After Single-Agent B-cell Maturation Antigen-Targeted Treatment in Multiple Myeloma: A Report of Three Cases in Sheikh Shakhbout Medical City

“…Belantamab mafodotin BCMA-targeted therapy has been considered a potential “off-the-shelf” drug that can be administered immediately in an outpatient setting. Real-world data have reported outcomes comparable with the DREAMM-2 trial in terms of objective response rate (33-45%), median progression-free survival (PFS) (2-6.5 months), and median overall survival (OS) (6-18 (not-reached) months) [ 12 - 14 ]. However, we did not see a similar response in our patients, as they did not respond to belantamab mafodotin treatment, and their disease rapidly progressed.…”