P17: DARATUMUMAB (D) PLUS LENALIDOMIDE (R) 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: DRd is a combination regimen approved for the treatment of RRMM. We report here a multicenter retrospective analysis of 127 consecutive patients (63 F and 64 M) with symptomatic RRMM, from January 2018 to December of 2020 treated with DRd as salvage therapy, regardless of age, comorbidities, impaired kidney function and reduced bone marrow reservoir. Our cohort represents a patients population closer to real world clinical practice. Patients: The median age at diagnosis was 66 years (32-83). The median age at the start of DRd was 70.2 years (41-85). The median time to the start of DRd from diagnosis was 3 years (0-19). The median therapy lines received were 1 (1-4). 49 patients (38.6%) had previously undergone single or tandem ASCT. The last treatment received before the D-based regimen was VMP (35%) or VTd (32%). 93 patients (73.2%) had relapsed MM and 34 (26.8%) patients had refractory MM. 80.3% of MM relapsed patients had been previously exposed to only one therapy. Results: After a median follow-up of 28 months from the start of study treatment, the median number of cycles administered was 12 (1-33). The ORR was 86.5% with CR 30.2%, VGPR 33.6%, PR 22.7%. Surprisingly, an encouraging ORR was observed also in the 13% of L-refractory patients: 75% (CR 25%, VGPR 19%, PR 31%). Median TTR was 1 month (1-7). Best response was achieved at a median number of 5 cycles. Median TTP and median OS were not reached (1-year OS: 85.9%; 2-years OS: 73.7%). Both OS and TTP were significantly affected by “the high-quality response” (p <0.001). TTP was worst for those who had received ≥ 2 prior lines of treatments vs those who had received < 2 lines of treatment (p 0.07), but the “number of prior lines of treatment” is far from the p-value significance threshold. “Baseline disease status” and “age at starting treatment” did not affect either OS or TTP. R was reduced to 15 or 10 mg for haematological toxicities (19%) and non-haematological toxicities (renal failure 6%, gastrointestinal toxicity 6%, skin rash 5%, musculoskeletal toxicity 4%, thrombotic events 3%), while a delay before subsequent course administration was recorded because of neutropenia (18%), infections (15%), diarrhoea (5%) and thrombotic events (2%). 20.6% of patients discontinued treatment because of relapse, and 3.2% for haematological toxicities. After a median follow-up of 12 months from the start of study treatment, grade 3/4 neutropenia (36%) was the most common haematological toxicity. After a median follow-up of 28 months from the start of treatment, grade 3/4 neutropenia (37.7%) continues to be the most common haematological adverse event. As regards non-haematological adverse events, after a median follow-up of 12 months, fatigue (32%) was the most common, while FUO/infections occurred in 15% of patients, skin rash and deep vein thrombosis in 7% of patients. After a median follow-up of 28 months, fatigue (24.8%) and FUO/infections (17.3%) continue to be the most common non-haematological adverse events and diarrhoea occurred in 5.8% of patients. Conclusion: In our experience, the ORR was lower than what was previously reported in the POLLUX trial (ORR 86.5% vs 93%). The lower ORR observed could be related to a less selected population. In fact, in our survey, no exclusion criteria were applied. In addition, unfortunately, the interference of D with immunofixation and serum protein electrophoresis assays may lead to an underestimation of CR.