Compassionate Use of Belantamab Mafodotin for Treatment of Patients with Relapsed/Refractory Multiple Myeloma Heavily Treated. Spanish Experience

Abstract

Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

Impact of belantamab mafodotin‐induced ocular toxicity on outcomes of patients with advanced multiple myeloma

“…Although this study did not specify the nature of the toxicities leading to the treatment discontinuation, 15% of patients stopped therapy due to adverse effects. 13 Interestingly, in a study involving patients with triple-refractory MM who received BLMF in combination with dexamethasone, the rates of treatment-emergent keratopathy were similar (82%, with 56% demonstrating grade ≥3 keratopathy) to the rates of the DREAMM-2 study, underscoring that the concomitant use of systemic steroids failed to reduce the risk of ocular toxicity. In this study, 68% of patients required keratopathy-related dose reduction or delays, although the number of patients in whom the disease had consequently progressed was not specified.…”

“…In another study which included 33 patients treated with BLMF monotherapy outside of clinical trials, keratopathy developed in 52% of the cohort. Although this study did not specify the nature of the toxicities leading to the treatment discontinuation, 15% of patients stopped therapy due to adverse effects 13 . Interestingly, in a study involving patients with triple‐refractory MM who received BLMF in combination with dexamethasone, the rates of treatment‐emergent keratopathy were similar (82%, with 56% demonstrating grade ≥3 keratopathy) to the rates of the DREAMM‐2 study, underscoring that the concomitant use of systemic steroids failed to reduce the risk of ocular toxicity.…”

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

“…Therefore, the realworld data from those patients unable to participate in a clinical trial but that have received BM under the US Expanded Access Program (EAP; NCT03763370), or the expanded access compassionate care program in Europe, are being analyzed. However, little data has yet been published [12,[17][18][19][20][21][22], mainly from scientific meetings.…”