Real-World Effectiveness and Safety of Belantamab Mafodotin Monotherapy in Triple-Class Refractory Multiple Myeloma

Abstract

B-cell maturation antigen (BCMA) is a promising therapeutic target for multiple myeloma (MM). The aim of this study was to assess the effectiveness and tolerability of monotherapy with the conjugated anti-BCMA monoclonal antibody belantamab mafodotin in triple-class refractory patients with MM in real-world practice. Patients refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 monoclonal antibody received belantamab mafodotin at 2.5 mg/kg intravenously every 3 weeks. Overall, 27 patients with a median age of 65 years (range 41–81) were included. Of these, 52% were male and the median number of prior lines of treatment was 5 (4–10). The overall response rate (partial response or better) was 52%, whereas the disease control rate (stable disease or better) was 70%. The median progression-free survival (PFS) was 2 months (95%CI: 0–7), whereas the median PFS among the responders was 12 months (95%CI: 6–18). Regarding the toxicity profile, the most common toxicity was eye toxicity, in 44% of the patients. Keratopathy grade 2–3 was reported in 33.3% of the patients. In conclusion, belantamab mafodotin showed a safety and efficacy profile consistent with the results of the registrational study. Importantly, heavily pretreated patients who responded to treatment derived a substantial survival benefit.

Treatment with low‐dose, single‐agent belantamab mafodotin is safe and provides long‐term responses in heavily pretreated multiple myeloma patients

“…According to our analysis, most patients responded and improved their responses over the first few months of therapy, reaching VGPR/CR. These results, which are superior to those reported in most prospective and retrospective real‐world studies, 1,4,5,7,8,14,15 might reflect the decreased ocular toxicity achieved with our low‐dose belantamab strategy, enabling continues treatment and deepening of response. These deep responses were translated into prolonged PFS 3 …”

Belantamab mafodotin in triple‐refractory multiple myeloma patients: A retro‐prospective observational study in Italy

“…Among European studies [6,11,18,20,28], the Spanish [18] and French [20] In our study, outcome measures were affected by age, ECOG PS, and response to belantamab. We found no differences in terms of PFS and OS between patients younger than 70 years and 70 years or older.…”

“…Only 3% of patients in both arms permanently discontinued treatment due to ocular toxicities. Recently several studies on belantamab mafodotin as monotherapy in the real‐life context have been published, showing an ORR ranging from 27% to 52% [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Results of these studies are summarized in Table 1 .…”

Belantamab mafodotin, lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma: Part 1 results of a phase I/II study

“…On the contrary, keratopathy rates ranged from 32% to 72% across clinical trials and real-world studies in heavily pretreated RRMM patients who received belamaf monotherapy. [19][20][21][22][23]34 However, the lowest reported rates in real-world studies should be interpretated with caution, because the patient adherence to monthly ophthalmological assessments and the ophthalmological expertise may differ significantly among studies. Furthermore, considering the pattern of development of belamafassociated keratopathy, 34 we estimate that the clinical manifestation of keratopathy follows the temporal pattern of eye itching when keratopathy is ≤Gr1, while visual acuity declines when keratopathy progresses to ≥Gr2.…”

“…18 Real-world studies of belamaf monotherapy provided similar results with a marked survival benefit among responders. [19][20][21][22] Moreover, although belamaf monotherapy was not statistically superior to pomalidomide with dexamethasone in terms of PFS prolongation (11.2 versus 7 months, respectively, p=0.56) in the DREAMM-3 study including RRMM patients with at least two prior lines of therapy, the responses were deeper and more durable with belamaf. 23 In terms of safety, a common belamaf-related adverse event is ocular toxicity, which is usually reversible but may require long-term use of supportive eye medications.…”