S1602 CARFILZOMIB AND DEXAMETHASONE MAINTENANCE PROLONG TIME TO PROGRESSION

Abstract

Background:Salvage autologous stem cell transplantation (ASCT) is used in selected patients with relapsed multiple myeloma after up‐front ASCT. There is strong support for the use of maintenance therapy after upfront ASCT in newly diagnosed multiple myeloma whereas data on maintenance therapy after salvage ASCT are sparse.The Nordic Myeloma Study Group (NMSG) initiated the CARFI trial (NCT02572492), an open randomized phase II study, to investigate the efficacy and safety of carfilzomib as part of induction and conditioning in salvage ASCT and to evaluate the role of carfilzomib/dexamethasone maintenance after salvage ASCT. We report here response and safety data on 168 patients randomized to maintenance treatment with carfilzomib and dexamethasone or to observation.Aims:To report response and safety data in 168 patients randomized to maintenance with carfilzomib‐dexamethasone or observation following salvage ASCT.Methods:Patients with first relapse after up‐front ASCT were treated with an induction regime containing four cycles of CAR‐CY‐DEX (iv carfilzomib 20 mg/sqm → 36 mg/sqm on days 1, 2, 8, 9, 15 and 16, tablet cyclophosphamide 300 mg/sqm on days 1, 8 and 15 and tablet dexamethasone 20 mg on days 1, 2, 8, 9, 15 and 16 in each 28‐days cycle). The subsequent conditioning regimen contained iv carfilzomib 27 mg/sqm on day –2 and –1, and iv melphalan 200 mg/sqm on day –2. The patients had not received any maintenance therapy after upfront ASCT. Two months after ASCT patients were randomized (1:1) to observation or maintenance therapy with iv carfilzomib 27 mg/sqm → 56 mg/sqm every second week and tablet dexamethasone 20 mg every second week. The randomization was stratified according to relapse 1 – 2 year or > 2 years after up‐front ASCT, ISS stage and standard versus high‐risk cytogenetics. Primary end‐point was to compare time to progression between carfilzomib‐dexamethasone maintenance and observation in patients treated with salvage ASCT.Results:200 patients were enrolled in the study and 32 of these went off study during the induction and after ASCT. The remaining 168 patients were randomized to carfilzomib‐dexamethasone (82 patients) or observation (86 patients). The median age was 62 (interquartile range: 56; 66) years and the median follow‐up from randomization was 10.7 (5.5 ‐ 18.6) months. The two groups were balanced regarding age, time from myeloma diagnosis, treatment at diagnosis, performance status, ISS stage and high‐risk cytogenetics. The median time to progression was 25.1 (95% CI: 24.4‐NR) months in the maintenance group and 18.9 (95% CI: 14.3–23.7) months in the observation group (hazard ratio 0.5 (95% CI: 0.3–0.8, P = 0.006)) (Figure I). A total of 47 serious adverse events (SAE) were reported in 24 patients on carfilzomib‐dexamethasone maintenance and 26 SAEs in 18 patients in the observation group. The majority of the SAEs were infections; 35 in the maintenance group and 21 in the observation group, divided into viral infection (10 versus 2), septicemia (2 versus 0) and pneumonia (10 versus 6). Three SAEs classified as cardiac related were observed in the maintenance group (syncope, atrial fibrillation and pulmonary embolism) in contrast to one in the observation group (dyspnea).Summary/Conclusion:Maintenance therapy with carfilzomib and dexamethasone maintenance prolongs median time to progression with approximately 6 months following salvage ASCT in multiple myeloma.image