MCL-002: UPDATED EFFICACY AND SAFETY RESULTS FOR LENALIDOMIDE VS. INVESTIGATOR’S CHOICE MONOTHERAPY IN RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA
Author(s): ,
Luca Arcaini
Affiliations:
Department of Molecular Medicine,University of Pavia,Pavia,Italy;Department of Hematology Oncology,Fondazione IRCCS Policlinico San Matteo,Pavia,Italy
,
Simon Rule
Affiliations:
Department of Hematology,Derriford Hospital,Plymouth,United Kingdom
,
Thierry Lamy
Affiliations:
Department of Hematology,Hôpital Pontchaillou,Rennes,France
,
Jan Walewski
Affiliations:
Department of Lymphoid Malignancies,Maria Sklodowska-Curie Memorial Institute and Oncology Centre,Warsaw,Poland
,
David Belada
Affiliations:
Fourth Department of Internal Medicine - Hematology,Charles University Hospital and Faculty of Medicine,Hradec Králové,Czech Republic
,
Jiri Mayer
Affiliations:
Department of Internal Medicine, Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
John Radford
Affiliations:
The University of Manchester and The Christie NHS Foundation Trust,Manchester,United Kingdom
,
Wojciech Jurczak
Affiliations:
Department of Hematology,Jagiellonian University,Krakow,Poland
,
Franck Morschhauser
Affiliations:
Centre Hospitalier Universitaire Régional de Lille,Lille,France
,
Julia Alexeeva
Affiliations:
Federal Medical Research Center,Saint Petersburg,Russian Federation
,
Tsvetan Biyukov
Affiliations:
Celgene International Sarl,Boudry,Switzerland
,
Meera Patturajan
Affiliations:
Celgene Corporation,Summit,United States
,
Marie-Laure Casadebaig Bravo
Affiliations:
Celgene International Sarl,Boudry,Switzerland
Marek Trněný
Affiliations:
Department of Hematology,Charles University Hospital,Prague,Czech Republic
EHA Learning Center. Arcaini L. Jun 9, 2016; 132699
Prof. Luca Arcaini
Prof. Luca Arcaini
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Abstract
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Abstract: E1150

Type: Eposter Presentation

Background
Although most patients with mantle cell lymphoma (MCL) respond to initial therapy, relapses are common and lead to increasingly shorter remissions. Lenalidomide, an IMiD® immunomodulatory agent with direct and immune-mediated mechanisms of action, has demonstrated efficacy and safety in relapsed/refractory (R/R) MCL in multiple studies, including heavily pretreated patients. 

Aims
Evaluate results after an additional 1 year of follow-up after primary analysis for the randomized MCL-002 (SPRINT) study comparing lenalidomide vs investigator’s choice (IC) monotherapy in R/R MCL patients.

Methods
MCL-002 is a multicenter, open-label study in MCL patients who had 1-3 relapses or failed prior therapy (including an alkylating agent and an anthracycline, and/or cytarabine, and/or fludarabine [± rituximab]) and were ineligible for intensified chemotherapy or stem cell transplantation (NCT00875667). Upon informed consent, oral lenalidomide was initiated at 25 mg/day on days 1-21 of 28-day cycles until disease progression or as tolerated. IC treatment included single-agent rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. The primary endpoint was progression-free survival (PFS, central review per modified 1999 IWG criteria); secondary endpoints included ORR, time to response, OS, and safety. Post-primary analysis (07March2014) all subsequent analyses are based on investigator’s assessment.

Results
254 patients were randomized 2:1 to lenalidomide (n=170) or IC (n=84). As of the current data cut-off of March 7, 2015, 21 (12%) patients remain on lenalidomide and 2 (2%) patients on IC. With an additional 1 year of follow-up from the primary analysis (median 21.0 month follow-up [range, 0.02-69.6]), the median PFS by investigator assessment continues to show improvement for lenalidomide over IC (8.6 vs 5.4 months, respectively), with an HR=0.67 (95% CI, 0.48-0.89; sequential log-rank P=0.012). Response rates showed a similar trend with an ORR of 46% vs 23% (P<0.001) and CR/CRu of 12% vs 8% (P=0.336) for lenalidomide vs IC, respectively. Median time to best response was 5.9 vs 13.1 months and median OS was 27.8 vs 21.1 months. Among the safety population (250 patients receiving ≥1 dose of study drug), 68% of lenalidomide and 40% of IC patients with ≥1 adverse event (AE) had dose reductions/interruptions, in part due to a longer duration of lenalidomide treatment and strict dose modification requirements. At a median time of 2.9 months (range, 0.7-37.8) from randomization, 39 patients (46%) crossed over from IC to lenalidomide. The most common grade 3/4 AEs were neutropenia (45% for lenalidomide vs 34%% for IC, without increased risk of infection), thrombocytopenia (20% vs 28%), anemia (9% vs 7%), and leukopenia (8% vs 11%). Nonhematologic AEs with lenalidomide were primarily grade 1/2. Any-grade tumor flare reaction was observed in 10% of lenalidomide patients (2% grade ≥3), and 1 patient in each arm experienced tumor lysis syndrome. Invasive second primary malignancies were identified in 4% of lenalidomide and 5% of IC patients.

Conclusion
Lenalidomide continues to show significantly improved PFS and ORR by investigator assessment compared with IC in patients with R/R MCL, which was similar to previous central review. The consistent safety profile of lenalidomide partly reflected longer treatment exposure; AEs were manageable with dose modifications or supportive therapy. Overall, long-term follow-up of the MCL-002 trial confirms the improved efficacy of lenalidomide relative to IC monotherapy in patients with R/R MCL.

Session topic: E-poster

Keyword(s): Mantle cell lymphoma
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