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

SummaryPatients 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.

Current overview and treatment of mantle cell lymphoma

“…A multicenter open-label phase III study demonstrated superiority of temsirolimus to investigator’s choice therapy with a median PFS of 4.8 months, leading to its approval in Europe 34 . Third, the phase II EMERGE trial confirmed the activity of lenalidomide in patients with progression of disease on bortezomib, with an overall response rate (ORR) of 28% in a heavily pre-treated population and durable efficacy with long-term follow-up, leading to lenalidomide’s approval in the US 31 , 35 . Subsequently, the SPRINT trial conducted by the European MCL Network randomized 254 patients to receive lenalidomide versus investigator’s choice treatment and found a median PFS of 8.7 months in the lenalidomide group compared with 5.2 months in the control population 36 .…”

Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma

“…The regimen consisted of an induction phase with 6 cycles of LBR (LEN [by mouth, days [1][2][3][4][5][6][7][8][9][10][11][12][13][14], bendamustine [90 mg/m 2 IV, days 1-2], rituximab [375 mg/m 2 IV, day 1]), cycle duration 28 days, followed by a maintenance phase with singleagent LEN (by mouth, days 1-21), cycle duration 28 days, up to a maximum of 7 cycles (total duration 52 weeks).…”

“…15 Rash is a common side effect of both bendamustine and LEN. [11][12][13][14][15][16]28 R-B was associated with a higher degree of cutaneous toxicity when compared with R-CHOP or R-CVP. 12,18,29,30 Concerning front-line LEN 1 rituximab in MCL, Ruan et al reported grade 3 to 4 rash in 29% of patients, in contrast to ,10% in relapsed/refractory non-Hodgkin lymphoma.…”

Molecular profiling and management of mantle cell lymphoma

“…36 Exploratory analyses showed that the proliferation index for Ki-67 (30% cutoff) was significantly associated with a lower CR rate, DOR, and survival in the MCL-001 study. 37 The combination of lenalidomide with other novel agents and with chemotherapy has been evaluated in numerous studies.…”