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

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.