P937: carfilzomib, lenalidomide plus dexamethasone (krd) in relapsed/refractory multiple myeloma patients: update analysis of real-life experience of gemmac group.

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Carfilzomib, lenalidomide, and dexamethasone (KRd) is approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). Aims: In this analysis, with a large number of patients included and longer follow-up time, we updated data of the efficacy and safety of KRd in a real-life cohort in fourteen hospitals from Catalonia. Methods: A real-life retrospective analysis of RRMM patients treated with KRd at hospitals in GEMMAC group from January 2016 until July 2020. KRd was administrated at standard schedule (carfilzomib 27mg/m2, d1,2,8,9,15,16; lenalidomide 25mg/d, d1-21 (adjusted by renal clearance); dexamethasone 20-40mg, d1,8,15,22). Response rate was assessed using IMWG criteria. Progression free survival (PFS) and overall survival (OS) were calculated from the start of KRd treatment using Kaplan-Meier method. Cytogenetic high-risk (HR) included t(4;14), t(14;16) or del(17p) vs. standard risk (SR). Results: We included 194 patients with a median age of 62 years (range 40-88); 56% were male. Fifty-seven(29%), 64(33%) and 64 (33%) patients were ISS1, ISS2 and ISS3, respectively. Cytogenetic information by FISH at diagnosis was available in 114 patients, of them 39(20%) had HR cytogenetic. Median prior lines of therapy were 1 (1-10), of them 153 (79%), 27 (14%) and 14 (7%) received one, two or more than two prior lines of therapy, respectively. All patients had previously received bortezomib, 110 (57%) patients immunomodulatory drugs (46% thalidomide, 15% lenalidomide) and 12 (6%) patients Daratumumab. Seventy-nine (41%) patients received a previous autologous stem cell transplantation (ASCT). The overall response rate (ORR) was 73% (52% ≥VGPR, 37% ≥CR) with a median time to best response of 6 months. One hundred sixty-three (84%) patients discontinued treatment, mainly due to progression, 71 patients (37%), and toxicity, 32 patients (16%). Thirty-five (18%) patients received consolidation with ASCT and 8 (4%) patients with allogeneic transplantation (AlloSCT). After a median of 32 months of follow-up, median PFS and OS were 26 (95% CI, 20-33) and 65 (95% CI, 43-87) months, respectively. As reported in Figure 1, PFS and OS was shorter in patients who received >2 prior lines of therapy (PFS: 27 (95% CI, 21-32) vs 4 (95% CI, 0-8) months, p=0.02; OS: 65 (95%CI, 36-94) vs 8 (95% CI, 1-15) months, p<0.01). PFS and OS were shorter in HR cytogenetic group patients but did not achieve statistically significance (PFS: HR 8 [95%CI, 0-18] vs SR 29 [95%CI, 14-43] months, p=0.11; OS: HR: 28 vs SR: 65 [95%CI, 35-96] months, p=0.1). Median PFS and OS in the subgroup of patients who were consolidated with ASCT or AlloSCT (43 [22%]) were significantly longer [PFS: 52 (95%CI,47-57) vs 16 (95%CI, 9-23) months, p<0.01; OS: not reached vs 40 (95%CI,25-54) months, p<0.01]. A small group of patients received KRd as rescue therapy to ASCT due to suboptimal response at first line of scheme (n=29); twenty-six (90%) patients improved response and proceeded to ASCT with a median PFS of 50 (95%CI,25-74) months. Haematological toxicity was the most frequent adverse event (anemia (35%), leukopenia (33%), thrombocytopenia (29%)). Infections occurred in 31% and cardiovascular events in 9% of patients. Thirty-two (16%) patients discontinued due to toxicity. Summary/Conclusion: In this update, we confirm that KRd is an effective therapy in patients with RRMM, especially in patients at first or second relapses. No increase or new toxicities have been observed with a longer follow-up in a real-life population. KRd is also effective as bridge regimen to ASCT in patients with suboptimal response to induction therapy.Figure 1. PFS (A) and OS (B) by prior lines of therapy Keywords: Multiple myeloma