Defining Unmet Need Following Lenalidomide Refractoriness: Real-World Evidence of Outcomes in Patients With Multiple Myeloma

Abstract

BackgroundThe treatment paradigm for multiple myeloma (MM) continues to evolve with the development of novel therapies and the earlier adoption of continuous treatments into the treatment pathway. Lenalidomide-refractory patients now represent a challenge with inferior progression free survival (PFS) reported to subsequent treatments. We therefore sought to describe the natural history of MM patients following lenalidomide in the real world.MethodsThis was a retrospective cohort review of patients with relapsed MM who received lenalidomide-based treatments in the U.K. Data were collected for demographics, subsequent therapies, treatment responses, survival outcomes and clinical trial enrollment.Results198 patients received lenalidomide-based treatments at a median of 2 prior lines of therapy at a median of 41 months (range 0.5-210) from diagnosis. 114 patients (72% of 158 evaluable) became refractory to lenalidomide. The overall survival (OS) after lenalidomide failure was 14.7 months having received between 0-6 subsequent lines of therapy. Few deep responses were observed with subsequent treatments and the PFS to each further line was < 7 months. There was a steep reduction in numbers of patients able to receive further treatment, with an associated increase in number of deaths. The OS of patients progressing on lenalidomide who did not enter a clinical trial incorporating novel agents was very poor (8.8 months versus 30 months, p 0.0002), although the trials group were a biologically fitter group.ConclusionThese data demonstrate the poor outcomes of patients failing lenalidomide-based treatments in the real world, the highlight need for more effective treatments.

Carfilzomib plus dexamethasone in patients with relapsed and refractory multiple myeloma: A retro‐prospective observational study

“…This statement also follows from the evaluation of the lenalidomide-exposed patients, with a median PFS of 10 months, and from data on lenalidomide-refractory patients. For the latter, in fact, the results in terms of PFS are consistent with the findings from randomized clinical trials (lenalidomide-refractory patients treated with Kd at the second or third relapse had a median PFS of 8.8 months 22 ) and from real world, 23 in a population considered to be at high risk (for which, even when treated with different regimens, the reported median PFS is about 9 months) and which still represents an unmet medical need to date. 24 We also consider the studied scheme to be valid considering the risk profile.…”

A real‐world retrospective–prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience

“…[24][25][26] As a result, the vast majority are Len-exposed and, more often, Len-refractory as early as at first relapse, raising the issue of the optimal placing of this Len-based triplet. 16,17 We therefore conducted a retrospective/prospective analysis to assess the efficacy and safety of IRd in a realworld population of 106 patients treated in 21 centers in the North of Italy between January 2017 and May 2021.…”

“…However, an increasing proportion of MM pts, both transplant eligible and non‐transplant eligible, receive Len‐based first line regimens until progression 24–26 . As a result, the vast majority are Len‐exposed and, more often, Len‐refractory as early as at first relapse, raising the issue of the optimal placing of this Len‐based triplet 16,17 …”

“…This raises the issue of the feasibility of this Len-based treatment in previously Len-exposed or refractory pts and the optimal placing within the current therapeutic scenario. 16,17 In this perspective, we conducted an observational analysis of 106 RRMM pts treated with IRd between January 2017 and May 2021 in 21 centers in Northern Italy, with the aim to evaluate efficacy and safety of IRd in a real-world population including a significant proportion of Len-refractory pts (20.7%) in addition to Len-exposed, non-refractory pts (36.8%). The issue of rechallenge with this all-oral, Len-based, triplet regimen, might be especially relevant for the elderly population, where frailty and comorbidities limit the therapeutic options in the relapsed/refractory setting.…”

Efficacy and safety of daratumumab, pomalidomide, and dexamethasone versus daratumumab, carfilzomib, and dexamethasone in daratumumab‐naïve relapsed multiple myeloma

“…7 Dara based combinations with lenalidomide or bortezomib have limited role in the relapsed settings given the common utilization of the latter in the induction and maintenance schema in United States, which leads to many patients being refractory to lenalidomide and/or bortezomib at first relapse. 8,9,10 On the contrary, combinations with pomalidomide or carfilzomib constitute favorable options in the early relapse settings, particularly for patients who are either naïve or sensitive (previously exposed but not refractory) to dara. After demonstrating safety and efficacy in the phase III CANDOR and APOLLO trials, DKd and DPd received approvals for the treatment of RRMM in patients who have received 1 prior line of therapy including lenalidomide and a proteasome inhibitor, respectively.…”