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.

4th Department of Internal Medicine Haematology Charles University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Clinical Research and Development Celgene Corporation Summit NJ USA

Clinical Research and Development Celgene Sàrl Boudry Switzerland

Department of Haematology Charles University Hospital Prague Czech Republic

Department of Haematology Derriford Hospital Plymouth United Kingdom

Department of Haematology Hôpital Claude Huriez EA 7365 GRITA Lille France

Department of Haematology Hôpital Pontchaillou Rennes France

Department of Haematology Jagiellonian University Medical College Kraków Poland

Department of Haematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Italy

Department of Haematology Research Federal Medical Research Centre Saint Petersburg Russia

Department of Internal Medicine Haematology and Oncology University Hospital Brno Brno Czech Republic

Department of Lymphoid Malignancies Maria Sklodowska Curie Memorial Institute and Oncology Centre Warsaw Poland

Department of Molecular Medicine University of Pavia Pavia Italy

Haematopathology Unit Hospital Clinic University of Barcelona Barcelona Spain

Serviço de Anatomia Patológica Instituto Português de Oncologia de Lisboa Francisco Gentil Lisboa Portugal

The University of Manchester and the Christie NHS Foundation Trust Manchester Academic Health Science Centre Manchester United Kingdom

Unit of Haematopathology European Institute of Oncology Milan Italy

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Avivi, I. & Goy, A. (2015) Refining the mantle cell lymphoma paradigm: impact of novel therapies on current practice. Clinical Cancer Research, 21, 3853–3861. PubMed

Cheson, B.D. , Horning, S.J. , Coiffier, B. , Shipp, M.A. , Fisher, R.I. , Connors, J.M. , Lister, T.A. , Vose, J. , Grillo‐Lopez, A. , Hagenbeek, A. , Cabanillas, F. , Klippensten, D. , Hiddemann, W. , Castellino, R. , Harris, N.L. , Armitage, J.O. , Carter, W. , Hoppe, R. & Canellos, G.P. (1999) Report of an international workshop to standardize response criteria for non‐Hodgkin's lymphomas. NCI Sponsored International Working Group. Journal of Clinical Oncology, 17, 1244–1253. PubMed

Dreyling, M. , Geisler, C. , Hermine, O. , Kluin‐Nelemans, H.C. , Le Gouill, S. , Rule, S. , Shpilberg, O. , Walewski, J. & Ladetto, M. (2014) Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow‐up. Annals of Oncology, 25(Suppl. 3), iii83–iii92. PubMed

Dreyling, M. , Jurczak, W. , Jerkeman, M. , Silva, R.S. , Rusconi, C. , Trneny, M. , Offner, F. , Caballero, D. , Joao, C. , Witzens‐Harig, M. , Hess, G. , Bence‐Bruckler, I. , Cho, S.G. , Bothos, J. , Goldberg, J.D. , Enny, C. , Traina, S. , Balasubramanian, S. , Bandyopadhyay, N. , Sun, S. , Vermeulen, J. , Rizo, A. & Rule, S. (2016) Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle‐cell lymphoma: an international, randomised, open‐label, phase 3 study. Lancet, 387, 770–778. PubMed

Goy, A. , Sinha, R. , Williams, M.E. , Kalayoglu Besisik, S. , Drach, J. , Ramchandren, R. , Zhang, L. , Cicero, S. , Fu, T. & Witzig, T.E. (2013) Single‐agent lenalidomide in patients with mantle‐cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL‐001 (EMERGE) study. Journal of Clinical Oncology, 31, 3688–3695. PubMed PMC

Goy, A. , Kalayoglu Besisik, S. , Drach, J. , Ramchandren, R. , Robertson, M.J. , Avivi, I. , Rowe, J.M. , Herbrecht, R. , Van Hoof, A. , Zhang, L. , Cicero, S. , Fu, T. & Witzig, T. (2015) Longer‐term follow‐up and outcome by tumour cell proliferation rate (Ki‐67) in patients with relapsed/refractory mantle cell lymphoma treated with lenalidomide on MCL‐001(EMERGE) pivotal trial. British Journal of Haematology, 170, 496–503. PubMed PMC

Gribben, J.G. , Fowler, N. & Morschhauser, F. (2015) Mechanisms of action of lenalidomide in B‐cell non‐Hodgkin lymphoma. Journal of Clinical Oncology, 33, 2803–2811. PubMed PMC

Habermann, T.M. , Lossos, I.S. , Justice, G. , Vose, J.M. , Wiernik, P.H. , McBride, K. , Wride, K. , Ervin‐Haynes, A. , Takeshita, K. , Pietronigro, D. , Zeldis, J.B. & Tuscano, J.M. (2009) Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. British Journal of Haematology, 145, 344–349. PubMed

Hess, G. , Herbrecht, R. , Romaguera, J. , Verhoef, G. , Crump, M. , Gisselbrecht, C. , Laurell, A. , Offner, F. , Strahs, A. , Berkenblit, A. , Hanushevsky, O. , Clancy, J. , Hewes, B. , Moore, L. & Coiffier, B. (2009) Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. Journal of Clinical Oncology, 27, 3822–3829. PubMed

Hess, G. , Coiffier, B. , Crump, M. , Gisselbrecht, C. , Offner, F. , Romaguera, J. , Kang, L. & Moran, P.J. (2015) Effect of prognostic classification on temsirolimus efficacy and safety in patients with relapsed or refractory mantle cell lymphoma: a retrospective analysis. Experimental Hematology & Oncology, 4, 11. PubMed PMC

Hoster, E. , Dreyling, M. , Klapper, W. , Gisselbrecht, C. , van Hoof, A. , Kluin‐Nelemans, H.C. , Pfreundschuh, M. , Reiser, M. , Metzner, B. , Einsele, H. , Peter, N. , Jung, W. , Wormann, B. , Ludwig, W.D. , Duhrsen, U. , Eimermacher, H. , Wandt, H. , Hasford, J. , Hiddemann, W. & Unterhalt, M. (2008) A new prognostic index (MIPI) for patients with advanced‐stage mantle cell lymphoma. Blood, 111, 558–565. PubMed

Hoster, E. , Klapper, W. , Hermine, O. , Kluin‐Nelemans, H.C. , Walewski, J. , van Hoof, A. , Trneny, M. , Geisler, C.H. , Di Raimondo, F. , Szymczyk, M. , Stilgenbauer, S. , Thieblemont, C. , Hallek, M. , Forstpointner, R. , Pott, C. , Ribrag, V. , Doorduijn, J. , Hiddemann, W. , Dreyling, M.H. & Unterhalt, M. (2014) Confirmation of the mantle‐cell lymphoma international prognostic index in randomized trials of the European mantle‐cell lymphoma network. Journal of Clinical Oncology, 32, 1338–1346. PubMed

Trneny, M. , Lamy, T. , Walewski, J. , Belada, D. , Mayer, J. , Radford, J. , Jurczak, W. , Morschhauser, F. , Alexeeva, J. , Rule, S. , Afanasyev, B. , Kaplanov, K. , Thyss, A. , Kuzmin, A. , Voloshin, S. , Kuliczkowski, K. , Giza, A. , Milpied, N. , Stelitano, C. , Marks, R. , Trumper, L. , Biyukov, T. , Patturajan, M. , Bravo, M.L. & Arcaini, L. (2016) Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL‐002; SPRINT): a phase 2, randomised, multicentre trial. The Lancet. Oncology, 17, 319–331. PubMed

Wang, M.L. , Blum, K.A. , Martin, P. , Goy, A. , Auer, R. , Kahl, B.S. , Jurczak, W. , Advani, R.H. , Romaguera, J.E. , Williams, M.E. , Barrientos, J.C. , Chmielowska, E. , Radford, J. , Stilgenbauer, S. , Dreyling, M. , Jedrzejczak, W.W. , Johnson, P. , Spurgeon, S.E. , Zhang, L. , Baher, L. , Cheng, M. , Lee, D. , Beaupre, D.M. & Rule, S. (2015) Long‐term follow‐up of MCL patients treated with single‐agent ibrutinib: updated safety and efficacy results. Blood, 126, 739–745. PubMed PMC

Zinzani, P.L. , Vose, J.M. , Czuczman, M.S. , Reeder, C.B. , Haioun, C. , Polikoff, J. , Tilly, H. , Zhang, L. , Prandi, K. , Li, J. & Witzig, T.E. (2013) Long‐term follow‐up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL‐003 study. Annals of Oncology, 24, 2892–2897. PubMed PMC