Carfilzomib-Revlimid-Dexamethasone Vs. Carfilzomib-Thalidomide-Dexamethasone Weekly (After 2 Twice Weekly Cycles) Followed By Carfilzomib Maintenance Vs. Control in Transplant Non-Eligible Patients with Newly Diagnosed Multiple Myeloma (NDMM) - Interim Efficacy Analysis of Combined Data (AGMT MM-02): American Society of Hematology, 61th Annual Meeting, scientific session

Introduction: Recent data from the ARROW and CHAMPION-1 study show significant activity of once weekly carfilzomib administration. Furthermore, the recent MUK5 and CARF studies show significantly increased PFS with carfilzomib maintenance therapy. Here, we compare 9 cycles of weekly KRd with weekly KTd (after 2 cycles of biweekly therapy) followed by a second randomization to 12 cycles of carfilzomib maintenance or observation only in elderly NDMM.Methods: 75 of 146 planned pts (median age: 75 years, range 55-84) with NDMM have been enrolled so far in this randomized phase 2 study. Treatment regimen: Carfilzomib 20mg/m2 on day 1+2, 27mg/m2 on day 8, 9, 15 and 16; cycle 2: 27mg/m2 on day 1,2,8,9,15 and 16; Carfilzomib was switched to once weekly dosing (56mg/m2, d1, 8, 15) from cycle 3 on until cycle 9. Patients received dexamethasone weekly (20mg in pts ≥75 years) and either lenalidomide 25mg d 1-21, or thalidomide 100mg/day, day 1-28 (50mg in pts ≥75 years). Patients with ≥SD after 9 cycles were randomized to carfilzomib 56mg/m2 (or last tolerated dose) on day 1 and 15 q 4 weeks, or to control for one year. FISH testing was done according recommended standards. NGF MRD testing was done in pts reaching CR or VGPR. Survival estimates were calculated according to Kaplan-Meier. Differences in response rate were assessed using Fisher's exact test, while the Log-Rank test was used for evaluating differences in survival. This trial is registered on clinicaltrials.gov (NCT02891811).Results: Median follow up was 11.7 months. 58 of the 75 pts completed ≥2 cycles (per protocol population (PP)), 12 pts discontinued therapy within the first 2 cycles due to AE/unacceptable toxicity [4 (5.3%)], death [3 (4%)], investigator decision [2 (2.7%)], patient's decision [2 (2.7%)], or other reason [1 (1.3%)]. As the trial is still ongoing, response rates and survival data are given for both groups (KRd and KTd) combined. Overall response was noted in 56 of the 58 pts (96.6%) with response data available, CR in 21 (36.2%), VGPR in 22 (37.9%), PR in 13 (22.4%), and MR in 2 (3.4%) pts. Of the 17 pts with MRD testing available, 47.1% achieved MRD negativity. PFS was 22.3 months in both the PP and ITT pts. Overall survival at 24 months was 78% in the ITT and 79% in the PP group, respectively.Between very elderly pts 75 years of age or older and pts below 75 years, no difference in ORR (96.8% vs. 96.3%, p=1), ≥VGPR (67.7% vs. 81.5%, p=0.3678) and PFS was found (ITT group: 22.3 months vs. not reached, p=0.926; PP group: 22.3 months vs. not reached, p=0.895). Likewise, OS did not differ in both age groups (data not shown). Outcome was also similar between pts with and without high-risk cytogenetics: ORR 100% vs.97.1%, p=1; ≥VGPR 80% vs. 71.4%, p=1; PFS not reached vs. 22.3 months, p=0.342; OS at 24 months was 85% for high-risk and 67% for standard-risk pts.In a safety evaluation with 66 patients, the most frequent grade 3/4 hematologic adverse events were anemia (4.5%), leukopenia (1.5%), and thrombocytopenia (6.0%). The non-hematologic grade 3/4 AEs were infections (21.2%), cardiac failure, gastrointestinal disorders, and renal impairment (6.0% each), neurologic disorders, hypertension, and rash (3.0% each), and hepatic failure, SPM, VTE, and psychiatric disorders (1.5% each).Conclusion: Once weekly carfilzomib 56mg/m² in combination with either lenalidomide or thalidomide resulted in high response rate and deep responses including MRDneg status in 47.1% of tested elderly patients with NDMM. Results were similar in very elderly pts (³75 years) and in those aged