P-303: BELANTAMAB MAFODOTIN IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA WHO ARE TRIPLE-REFRACTORY: A RETRO-PROSPECTIVE ITALIAN OBSERVATIONAL STUDY

Introduction: Recent therapeutic advances in multiple myeloma (MM) patients have dramatically improved patients’ outcomes. But drug resistance is an emerging challenge resulting in a poor survival with the urgent need for effective therapies, mostly in triple-refractory MM. Belantamab mafodotin (belamaf), the first-in-class antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), demonstrated efficacy in monotherapy in DREAMM-2 trial and was approved for relapsed/refractory MM (rrMM) patients with at least four previous lines of therapy (LOT).

Methods: Being belamaf real-world data scarce, we designed a retro-prospective study aiming to evaluate its efficacy and safety in rrMM patients treated in compassionate use programmes as Named Patient Program (NPP) and Expanded Access Program (EAP) in Italy, under the aegis of European Myeloma Network (EMN). The primary endpoint was the rate of patients achieving a clinical benefit (at least minimal response according to IMWG criteria). Secondary endpoints were safety, ORR (at least PR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Eligible criteria were: ≥18 years of age, MM diagnosis according to IMWG criteria, triple-refractoriness (at least one PI, one IMID and one anti-CD38 mAb) and at least 4 prior LOTs.

Results: Overall, 67 patients have been enrolled by 18 Italian centers, with a median age of 66 years (range 42-82), a median of 6 prior LOT (4-10), ECOG < 2 in 65% of patients and IgG, IgA and light chain in 60%, 19% and 21% of cases, respectively. High risk cytogenetic was observed in 22.4% and ISS3 stage in 37% of cases. CBR was 37%, ORR 31% and ≥SD 71%. After a median follow up of 12 months, median PFS was 3.7 months, median OS 12.8 months and median DoR 13.8 months. As for safety, the most frequent adverse events (AE) were ocular: corneal toxicity in 74% of patients and ocular symptoms in 16%, but only 10% had changes in BCVA. They recovered in 46% of cases, they requested drug discontinuation in 45% and only dose reduction in 13% of cases. Thrombocytopenia was described in 87.5% of patients, 50% of them grade 3, but reversible. Then, 8 infections, 4 infusion reactions, one pulmonary embolism and one grade 5 secondary neoplasia were reported. Belamaf was globally discontinued in 37 patients (55%), due to disease progression in 28, death in 3, toxicity in 5, other in 1 patient. Twenty-seven patients (40%) are still alive and 40 (60%) patients died (82.5% for disease progression, 10% for adverse events and 7.5% others). Explorative univariate Cox regression analysis suggests that PFS was negatively affected by age>65, p=0.094 and ECOG≥2, p=0.012

Conclusions: In conclusion, our cohort had fewer previous LOTs but similar median age than DREAMM-2 population. We found similar ORR, OS and safety profile, but median PFS and DOR seem to be longer. PFS seems to be not affected by classical disease prognostic factors but by baseline patient characteristics.