P18: DARATUMUMAB (D) PLUS BORTEZOMIB (V) AND DEXAMETHASONE (D) AS SALVAGE THERAPY FOR PATIENTS WITH REFRACTORY/RELAPSED MULTIPLE MYELOMA (RRMM): INITIAL FOLLOW-UP OF AN ITALIAN MULTICENTER RETROSPECTIVE CLINICAL EXPERIENCE BY “RETE EMATOLOGICA PUGLIESE”
Authors: G Mele, N Cascavilla, N Di Renzo, A Guarini, P Mazza, L Melillo, V Pavone, G Tarantini, P Curci, AP Falcone, C Germano, A Mele, G Palazzo, G Palumbo, G Reddiconto, B Rossini, G Specchia, P Musto, D Pastore
Journal: HemaSphere (2022)

Introduction: Real-life reports of experiences with D-based combination therapies in RRMM are very limited. We report herein a multicenter retrospective analysis of 65 consecutive patients (M 59.4%, F 40.6%) with symptomatic RRMM, from January 2018 to December of 2020, treated with DVd as salvage therapy at 9 haematological centers in Puglia. Patients: The median age at diagnosis was 62.5 years (range 36-81). The median age at the start of DVd from diagnosis was 68.1 years (range 40-81). The median time to the start of DVd from diagnosis was 4 years (range 0-16). The median therapy lines received were 3 (range 1-6). 38 patients (58%) had previously undergone single or tandem ASCT. The patients were previously exposed to V (93%) and carfilzomib (32%), in addition to a prior exposure to IMIDs (Len 78%, Thal 41%, Pom 8%). The last treatment received before the DVd regimen was KRd (29%) or Rd (26%). 52 (80%) patients had relapsed MM, while 13 (20%) patients had refractory MM. 73.9% of MM relapsed patients had been heavily treated. Results: After a median follow-up of 28 months from the start of study treatment, the median number of cycles administered was 8 (range 1-34). 7% of patients required dose reduction/adjustment (V to 1 mg/m2) for peripheral neuropathies (5%) and thrombocytopenia (2%), respectively, while 25% of patients were shifted to a weekly schedule of V and d for haematological toxicities (14% thrombocytopenia, 11% neutropenia), and 5% for constipation. 55.4% of patients discontinued treatment due to relapse. The ORR was 72.6% (CR 8.1%, VGPR 19.3%, PR 45.2%). Median TTR was 1.5 months (range 1-9). Best response was achieved at a median number of 5 cycles. Median TTP was 10.8 months (95%-CI: 7.1-13.8). Median OS was not reached (1-year OS: 70.2%; 2-years OS: 58.9%). OS was significantly affected both by “the high-quality response” (p <0.001) and “number of prior lines of treatment” (p 0.02), while TTP was significantly affected only by the “high-quality response” (p <0.001). “Baseline disease status” and “age at starting treatment” did not affect either OS or TTP. We evaluated haematological and non-haematological toxicities after a median follow-up of 12 and 28 months. After a median follow-up of 12 months from the start of study treatment, grade 3/4 thrombocytopenia (26%) was the most common haematological toxicity. After a median follow-up of 28 months from the start of treatment, grade 3/4 thrombocytopenia (27.6%) continues to be the most common haematological adverse event. As regards non-haematological adverse events, after a median follow-up of 12 months, FUO/infections (32%) were the most common non-haematological adverse event. After a median follow-up of 28 months, FUO/infections (15%) continue to be the most common non-haematological adverse event, although the incidence rate has reduced by half, and constipation occurred in 7.6% of patients. Conclusions: The ORR, in our experience, was lower than what was previously reported in the CASTOR trial (ORR 72.6% vs 85%). The following imperative considerations must be pointed out. First, the lower ORR observed in our small experience could be related to a less selected population. Second, the majority of patients 1) were heavily pretreated, 2) had been previously exposed to at least one proteasome inhibitor and 3) had previously undergone continuous treatment with KRd or Rd. Nevertheless, encouraging out-comes were observed, suggesting that patients can benefit from this effective therapy even at advanced lines of therapy.