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

Abstract

Carfilzomib–lenalidomide–dexamethasone (KRd) has been approved for the treatment of relapsed/refractory multiple myeloma (RRMM). We conducted a retrospective analysis of 197 RRMM patients (pts) between January 2016 and March 2018 in six Italian hematologic centers, with the aim to evaluate efficacy and safety of KRd in real‐life. At KRd initiation 27% carried high risk cytogenetic abnormalities (HRCA) [del17p and/or t(4;14) and/or t(14;16)], median number of prior lines of therapy was 2 (1–8), nearly all pts (96%) received prior bortezomib (18% refractory) while 45% were exposed to lenalidomide (R; 22% refractory). At the median of 12.5 months, 52% of the pts had discontinued treatment, mainly (66%) for progression. Main grade 3–4 adverse events were neutropenia (21%), infections (11%), and hypertension (6%). Overall, the response rate was 88%. The median progression‐free survival (PFS) was 19.8 months and 1‐year overall survival (OS) rate was 80.6%. By subgroup analysis, extended PFS and OS were observed for pts who received ≤2 prior lines of therapy (HR = 0.42, p < 0.001 and HR = 0.35, p = 0.001, respectively), not refractory to prior R (HR = 0.37, p < 0.001, and HR = 0.47, p = 0.024), without HRCA (HR = 0.33, p = 0.005 and HR = 0.26, p = 0.016) and achieving ≥ very good partial response (VGPR; HR = 0.17, p < 0.001 and HR = 0.18, p < 0.001). In conclusion, KRd demonstrated to be effective in RRMM pts treated in real‐world setting, without new safety concerns. Better survival outcomes emerged for pts with ≤2 prior lines of therapy, achieving at least a VGPR, and without HRCA.

Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib‐based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients

“…Information on the prognostic impact of prior resistance to BTZ and/or LEN in KRD therapy is also limited in real-world observational studies, [11][12][13] while such information is mostly lacking for KD therapy.…”

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma

“…Median PFS was 19.8 months and 1 year OS was 80.6% with an ORR of 88%. Increased PFS and OS rates were observed in patients who received less than two prior line of therapies and overall, this study indicated KRd to be an effective regimen against relapsed or refractory MM outside of clinical studies without the emergence of novel safety concerns ( 109 ).…”

“…Rochchi et al. ( 109 ), investigated the efficacy and safety of carfilzomib, dexamethasone and lenalidomide therapy in relapsed or refractory MM patients in real world involving 197 patients. Most reported grade 3 or higher AEs included neutropenia (21%), infections (11%) and hypertension (6%).…”

Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients

“…12 Similarly, the addition of elotuzumab to Rd reduced the risk of progression by 30%, with a gain of 4.5 progression-free months compared with the control arm. 14 In this current study, in the lack of a randomized KRd vs. EloRd trial, and with the well-known limitations and susceptibility to the bias of real-life suggestions, 17 we weighed the relative usefulness of one triplet over the other, comparing a multicenter retrospective EloRd cohort 18 with four multicenter retrospective KRd cohorts, [19][20][21][22] all including RRMM cases treated outside of clinical trials. This current clinical practice study's overall results demonstrate that KRd therapy offers a superior outcome than EloRd.…”

“…After twelve cycles, K was reduced (days 1, 2, 15, and 16) and prolonged beyond 18 cycles at the physician's discretion. [19][20][21][22] In all five cohorts (EloRd and KRd), the dose of each drug was adjusted according to drug recommendations in case of specific preexisting comorbidities. In cases of specific predefined hematological and non-hematological toxic events, drugs' dosages were reduced, according to the manufacturers' recommendations and medical choice.…”