A real-world comparative analysis of carfilzomib and other systemic multiple myeloma chemotherapies in a US community oncology setting

Abstract

Background:Most multiple myeloma (MM) patients ultimately progress, with remission duration decreasing after first relapse. Recently, novel agents have been approved for the treatment of relapsed MM. There is a paucity of real-world data on these treatments. We sought to compare time to next treatment (TTNT) in MM patients in their second line of therapy (LOT2), treated with common proteasome inhibitor (PI)-based triplets.Methods:Adult MM patients who received carfilzomib (K) between 1 November 2013 and 29 February 2016 at US Oncology Network (USON) clinics utilizing iKnowMed™ electronic health records (EHRs) were identified. Patients were included if they were ⩾18 years of age, not enrolled in clinical trials, had ⩾2 visits at a USON clinic and received LOT2 regimens consisting of: K+lenalidomide with steroid (KRd), bortezomib+lenalidomide with steroid (VRd), or bortezomib+cyclophosphamide with steroid (VCyd). TTNT was estimated from LOT2 initiation to LOT3 initiation using the Kaplan–Meier method, and hazard ratios (HRs) were estimated using Cox modeling.Results:A total of 718 patients received a K-containing regimen sometime during their MM treatment (LOT1 to LOT5). Of these, 156 patients received: KRd (n = 112; 71.8%), VRd (n =27; 17.3%), or VCyd (n = 17; 10.9%). Baseline characteristics were similar between groups (mean age: 64.8 years; 58% male). Median TTNT was longest for KRd [25.3 months; 95% confidence interval (CI): 19.71–NR], versus VRd or VCyd (VRd median TTNT: 10.2 months, 95% CI: 4.24–12.71; VCyd: 6.5 months, 95% CI: 3.02–12.78; log-rank p < 0.0001). The adjusted HR for KRd was 0.19 (95% CI: 0.11–0.37), compared with VRd.Conclusions:Considering the real-world nature of these data, the median TTNT observed with KRd was relatively consistent, with progression-free survival (PFS) for KRd observed in the phase III ASPIRE trial (median PFS: ITT population = 26.3 months; LOT2 = 29.6 months). Patients who received KRd at first relapse had significantly longer TTNT, compared with those on VRd or VCyd, confirming the value of KRd as an important treatment option for relapsed MM.

A real‐world efficacy and safety analysis of combined carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory multiple myeloma

“…Therefore, we conducted a retrospective analysis to highlight the efficacy and toxicity of real‐life KRd treatment in 197 RRMM patients, showing a good concordance both with published clinical trials 9,13,27 and additional real‐world comparative analyses of K‐based treatment 15,28 …”

Ixazomib-Lenalidomide-Dexamethasone in Routine Clinical Practice: Effectiveness in Relapsed/refractory Multiple Myeloma

“…Collectively, these data indicate real-world effectiveness with PI-Rd triplet regimens in the patient populations for which they are selected. Similarly to ixazomib, recent registry/observational studies as well as EMR/claims-based analyses of patients treated in the non-clinical trial setting also suggest similar median PFS/TTNT values with bortezomib-based [2,[21][22][23][24][25][26][27] and carfilzomib-based [2,21,24,25,[27][28][29][30][31][32] regimens to those seen in Phase III studies [33][34][35].…”

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life

“…Consideration of PROs and their potential impact on efficacy may be more critical in the real-world setting compared to the potentially more motivating environment of clinical trial participation. Data from randomized controlled trials may not always reflect results for patients undergoing treatment in routine clinical practice, although data on some regimens indicate that duration of therapy, PFS, and/or time to next therapy are maintained between real-world non-clinicaltrial data and clinical-trial data [79][80][81][82] , suggesting their efficacy translates into broader effectiveness 83 . There are multiple potential reasons for this 'efficacy-effectiveness gap' 80,83 , and real-world effectiveness is dependent on multiple other endpoints beyond what is measured in clinical studies 13 , all of which must be considered in order to produce the desired or intended result.…”