C063 | ISATUXIMAB-CARFILZOMIB-DEXAMETHASONE VERSUS DARATUMUMAB-POMALIDOMIDE-DEXAMETHASONE IN PATIENTS PROGRESSING AFTER LENALIDOMIDE MAINTENANCE: AN ITALIAN REAL-LIFE STUDY

In recent years, Isatuximab-Carfilzomib-Dexamethasone (Isa-KD) and Daratumumab-Pomalidomide-Dexamethasone (D-PD) have been recognized as the standard of care for the treatment of lenalidomide (len) refractory patients. However, in the pivotal trials, most patients were treated at second or later relapse, and the proportion of len refractory patients was highly variable and never included the whole population. Moreover, no single comparison between Isa-KD and D-PD has ever been performed. The aim of this observational study is to retrospectively and prospectively compare the outcomes of patients treated with Isa-KD or D-PD in a homogenous cohort of len refractory patients. Starting from a cohort of 326 patients followed in 31 Italian centers who received at least one autologous stem cell transplantation, progressed after Len maintenance, and were treated at first relapse, we selected 146 cases who received Isa-KD and 61 D-PD. Patients in the Isa-KD cohort were younger (median age 62 vs 66 years, p=0.0008), more previously treated with anti-CD38 monoclonal antibodies (10.3% vs 0, p=0.0065), and had symptomatic relapse (63.5% vs 44.3%, p=0.0135). No differences in overall response rates (ORR) and complete response (CR) rates were found between Isa-KD and D-PD treated cases (ORR: 84.8% vs 88.1%, p=0.6582; CR: 31.2% vs 23.7%, p=0.3099). With a median follow up of 16 months for Isa-KD and 12 months for D-PD, patients treated with Isa-KD showed a significant improvement in terms of median progression free survival (PFS) as compared to D-PD (23 vs 17 months, p=0.0436) while no difference in median overall survival (OS) was observed (not reached vs 40 months, p=0.4619). Isa-KD displayed better PFS in patients with high-risk cytogenetic (20 vs 9 months, p=0.0839) and in those with b2 microglobulin >3.5mg/L (not reached vs 9 months, p=0.0226). Considering the type of relapse, patients treated at biochemical relapse or with late relapse (>24 months from starting maintenance) benefit the most with Isa-KD regimen compared to D-PD (not reached vs 23 months, p=0.0024; not reached vs 13 months, p=0.0025, respectively). To our knowledge, this is the first single study comparing Isa-KD and D-PD in len refractory patients treated at first relapse. Within the limitation of a still incomplete follow-up, the data suggests that Isa-KD may improve PFS compared to D-PD, especially in patients with late or biochemical relapse and high-risk cytogenetic.