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.

Abstract

Patients with mantle cell lymphoma (MCL) generally respond to first-line immunochemotherapy, but often show chemoresistance upon subsequent relapses, with poor outcome. Several studies of the immunomodulator, lenalidomide, have demonstrated its activity in MCL including the MCL-001 study in relapsed/refractory patients who had failed defined prior therapies of anthracyclines or mitoxantrone, cyclophosphamide, rituximab and also bortezomib. We present here the long-term efficacy follow-up of the prospective phase II MCL-001 study (N = 134), including new exploratory analyses with baseline Ki-67 (MIB1), a biological marker of tumour proliferation. With longer follow-up, lenalidomide showed a 28% overall response rate [ORR; 8% complete response (CR)/CR unconfirmed (CRu)]. Median duration of response (DOR), progression-free survival and overall survival were 16·6, 4·0 and 20·9 months, respectively. Myelosuppression continued to be the most common grade 3/4 toxicity. Several studies of MCL patients treated with chemotherapy, rituximab and bortezomib have shown an inverse association between survival and Ki-67. Ki-67 data in 81/134 MCL-001 patients showed similar ORRs in both low (<30% or <50%) versus high (≥30% or ≥50%) Ki-67-expressing groups, yet lower Ki-67 levels demonstrated superior CR/CRu, DOR and survival outcomes. Overall, lenalidomide showed durable efficacy with a consistent safety profile in heavily pretreated, relapsed/refractory MCL post-bortezomib.

• Authors: Andre Goy, Sevgi Kalayoglu Besisik, Johannes Drach, Radhakrishnan Ramchandren, Michael J Robertson, Irit Avivi, Jacob M Rowe, Raoul Herbrecht, Achiel Van Hoof, Lei Zhang, Sherri Cicero, Tommy Fu, Thomas Witzig
• Journal: British journal of haematology (Br J Haematol) Vol. 170 Issue 4 Pg. 496-503 (Aug 2015) ISSN: 1365-2141 [Electronic] England
• PMID: 25921098 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Chemical References

• Angiogenesis Inhibitors
• Biomarkers, Tumor
• Ki-67 Antigen
• Thalidomide
• Lenalidomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (administration & dosage, adverse effects)
• Biomarkers, Tumor (metabolism)
• Cell Proliferation (drug effects)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Ki-67 Antigen (metabolism)
• Lenalidomide
• Lymphoma, Mantle-Cell (drug therapy, metabolism, mortality, pathology)
• Male
• Middle Aged
• Survival Rate
• Thalidomide (administration & dosage, adverse effects, analogs & derivatives)