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

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, 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

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.

Keywords: Ki-67; efficacy; lenalidomide; mantle cell lymphoma; safety.

© 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
MCL‐001 updated follow‐up for (A) duration of response (DOR), (B) progression‐free survival (PFS) and (C) overall survival (OS) (following lenalidomide in patients with relapsed or refractory mantle cell lymphoma.
Figure 2
Figure 2
MCL‐001 exploratory analysis of Ki‐67 expression and response following lenalidomide in patients with relapsed/refractory MCL: response rates at (A) 30% and (B) 50% cut‐off thresholds. CR/CRu, complete response/CR unconfirmed; ORR, overall response rate; PR, partial response; and SD, stable disease.
Figure 3
Figure 3
MCL‐001 exploratory analysis of Ki‐67 expression (30% and 50% cut‐offs) and (A) duration of response (DOR), (B) progression‐free survival (PFS) and (C) overall survival (OS). 95% CI, 95% confidence interval; HR, hazard ratio; NR, not reached.

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