Hang Quach, MBBS(Hons), SpecCertOC, FRACP, FRCPA, MD, Haematologist with clinical and research interests in multiple myeloma, in particular myeloma, lymphoma and myeloid disorders at St Vincent’s Health Melbourne  and University of Melbourne Australia. In this audio, she speaks about the EHA 2022 Abstract – Carfilzomib, Dexamethasone, And Daratumumab (Kdd) Vs Carfilzomib And Dexamethasone (Kd) In Relapsed/Refractory Multiple Myeloma (Rrmm): Frailty Subgroup Analysis Of The CANDOR Study.
History
Frailty scores based on age, comorbidities, and functional status can assist in identifying frail patients (pts) at risk of treatment-related toxicity or poor outcomes. An examination of carfilzomib-treated patients in the clinical trials ASPIRE, ENDEAVOR, and ARROW discovered that the efficacy and safety of carfilzomib regimens are constant regardless of frailty state (Facon Blood Adv 2020).
Targets
In the phase 3 CANDOR trial, assess effectiveness and safety across frailty subgroups in patients with RRMM treated with KdD vs Kd.
Methodology
This post-hoc analysis made use of CANDOR’s projected interim readout (June 15, 2020). (NCT03158688). Based on a frailty score of 0, 1, or 2, points were classified as fit, intermediate (int), or frail. The International Myeloma Working Group (IMWG) frailty index was used for scoring: the final score is based on age (0 if 75 years, 1 if 76-80 years, 2 if >80 years), modified Charlson Comorbidity Index (CCI [Facon Blood Adv 2020]) (0 if CCI 1, 1 if CCI >1), and Eastern Cooperative Oncology Group performance status (ECOG PS) (0 if ECOG PS= The hazard ratio (HR) and 95 percent confidence interval (CI) for progression-free survival (PFS) were determined using a stratified Cox proportional hazards model. The overall response rate (ORR) was described descriptively, with the odds ratio (OR) and 95 percent confidence interval (CI) computed using the Mantel-Haenszel technique. The Onyx Response Computer Algorithm evaluated response and progression using IMWG criteria.
Outcomes
Frailty status was roughly proportional between arms, with 27 and 35 percent of KdD and Kd, respectively, classified as fit, 43 and 36 percent int, 25 and 27 percent frail, and 5 and 2 percent unknown. Although baseline characteristics of the overall population were generally balanced, more patients had prior transplant in the KdD vs Kd arm for the int (65 percent vs 36 percent) and frail (41 percent vs 27 percent) subgroups, and fewer patients were lenalidomide exposed (37 percent vs 61 percent)/refractory (25 percent vs 46 percent) subgroup. The median length of treatment for KdD vs Kd was 99 weeks (wks) vs 68 weeks (wks) for fit patients, 82 weeks (wks) vs 31 weeks for int patients, and 51 weeks (wks) vs 21 weeks for frail patients. Not reached (NR) vs 17.6 months (HR 0.64, 95 percent CI 0.38–1.07) for fit, NR vs 11.1 months (HR 0.44, 95 percent CI 0.28–0.69) for int, and 18.5 vs 9.3 months (HR 0.66, 95 percent CI 0.38–1.14) for frail points For fit points, the ORR for KdD vs Kd arms was 89 percent vs 89 percent (OR 1.09, 95 percent CI 0.35–3.38), 87 percent vs 70 percent (OR 2.95, 95 percent CI 1.31–6.62), and 75 percent vs 54 percent (OR 2.39, 95 percent CI 1.09–5.22) (Figure). Treatment-emergent adverse events (TEAEs) of any grade occurred in more than 95% of patients across arms and subgroups. Grade 3 TEAEs occurred in 87 percent (KdD) and 70 percent (Kd) of fit pts, 84 percent and 71% of int pts, and 91 percent and 90% of frail pts, respectively. Fatal TEAEs occurred in 4% and 2% of fit patients, 11% and 9% of int patients, and 16% and 8% of frail patients in the KdD and Kd arms, respectively. Carfilzomib was discontinued in 25 percent vs 17 percent of fit patients, 22 percent vs 29 percent of int patients, and 35 percent vs 23 percent of frail patients due to TEAEs. Acute renal failure occurred in 0 fit patients, 3 percent vs 14 percent of int patients, and 8 percent vs 5 percent of frail patients, while infusion reactions occurred in 16 percent vs 2 percent of fit patients, 13 percent vs 4 percent of int patients, and 14 percent vs 13 percent of frail patients in the KdD vs Kd arms (Table).
Implication
PFS benefit with KdD vs Kd was evident across frailty categories, consistent with earlier results of effectiveness and safety benefits of KdD. The clinically significant ORR improvement in the fragile category may assist physicians in evaluating therapy options in this difficult group.