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Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma.

ABSTRACT: In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent-to-treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single-agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history.

SUBMITTER: Arcaini L

PROVIDER: S-EPMC5814930 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma.

Arcaini Luca L Lamy Thierry T Walewski Jan J Belada David D Mayer Jiri J Radford John J Jurczak Wojciech W Morschhauser Franck F Alexeeva Julia J Rule Simon S Cabeçadas José J Campo Elias E Pileri Stefano A SA Biyukov Tsvetan T Patturajan Meera M Casadebaig Bravo Marie-Laure ML Trnĕný Marek M

British journal of haematology 20171128 2

In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL w ...[more]

PMID: 29193019

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Project description:BackgroundThe observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance.MethodsThe primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria.ResultsOf 58 enrolled patients (median age, 71 years; range, 50-89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment. Most patients (88%) had received ≥ 3 prior therapies (median 4; range, 1-13). Median time from last dose of ibrutinib to the start of lenalidomide was 1.3 weeks (range, 0.1-21.7); 45% of patients had partial responses or better to prior ibrutinib. Primary reasons for ibrutinib discontinuation were lack of efficacy (88%) and ibrutinib toxicity (9%). After a median of two cycles (range, 0-11) of lenalidomide-based treatment, 17 patients responded (8 complete responses, 9 partial responses), for a 29% overall response rate (95% confidence interval, 18-43%) and a median duration of response of 20 weeks (95% confidence interval, 2.9 to not available). Overall response rate to lenalidomide-based therapy was similar for patients with relapsed/progressive disease after previous response to ibrutinib (i.e., ≥PR) versus ibrutinib-refractory (i.e., ≤SD) patients (30 versus 32%, respectively). The most common all-grade treatment-emergent adverse events after lenalidomide-containing therapy (n = 58) were fatigue (38%) and cough, dizziness, dyspnea, nausea, and peripheral edema (19% each). At data cutoff, 28 patients have died, primarily due to mantle cell lymphoma.ConclusionLenalidomide-based treatment showed clinical activity, with no unexpected toxicities, in patients with relapsed/refractory mantle cell lymphoma who previously failed ibrutinib therapy.Trial registrationClinicaltrials.gov identifier NCT02341781 . Date of registration: January 14, 2015.

Project description:PURPOSE:The aim of this open-label, first-in-setting, randomized phase III trial was to evaluate the efficacy of alisertib, an investigational Aurora A kinase inhibitor, in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS:Adult patients with relapsed/refractory PTCL-one or more prior therapy-were randomly assigned 1:1 to receive oral alisertib 50 mg two times per day (days 1 to 7; 21-day cycle) or investigator-selected single-agent comparator, including intravenous pralatrexate 30 mg/m2 (once per week for 6 weeks; 7-week cycle), or intravenous gemcitabine 1,000 mg/m2 or intravenous romidepsin 14 mg/m2 (days 1, 8, and 15; 28-day cycle). Tumor tissue (disease subtype) and imaging were assessed by independent central review. Primary outcomes were overall response rate and progression-free survival (PFS). Two interim analyses and one final analysis were planned. RESULTS:Between May 2012 and October 2014, 271 patients were randomly assigned (alisertib, n = 138; comparator, n = 133). Enrollment was stopped early on the recommendation of the independent data monitoring committee as a result of the low probability of alisertib achieving PFS superiority with full enrollment. Centrally assessed overall response rate was 33% for alisertib and 45% for the comparator arm (odds ratio, 0.60; 95% CI, 0.33 to 1.08). Median PFS was 115 days for alisertib and 104 days for the comparator arm (hazard ratio, 0.87; 95% CI, 0.637 to 1.178). The most common adverse events were anemia (53% of alisertib-treated patients v 34% of comparator-treated patients) and neutropenia (47% v 31%, respectively). A lower percentage of patients who received alisertib (9%) compared with the comparator (14%) experienced events that led to study drug discontinuation. Of 26 on-study deaths, five were considered treatment related (alisertib, n = 3 of 11; comparator, n = 2 of 15). Two-year overall survival was 35% for each arm. CONCLUSION:In patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.

Dataset Information

Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma.

Publications

Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma.

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