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.
John Theurer Cancer Center at HUMC, Hackensack, NJ, USA.
Andre
A
Goy
Istanbul University Faculty of Medicine, Istanbul, Turkey.
Sevgi
S
Kalayoglu Besisik
Medical University of Vienna, Vienna, Austria.
Johannes
J
Drach
Karmanos Cancer Institute, Detroit, MI, USA.
Radhakrishnan
R
Ramchandren
Indiana University Medical Center, Indianapolis, IN, USA.
Michael J
MJ
Robertson
Rambam Health Care Campus, Haifa, Israel.
Irit
I
Avivi
Shaare Zedek Medical Centre, Jerusalem, Israel.
Jacob M
JM
Rowe
Hôpital de Hautepierre, Strasbourg, France.
Raoul
R
Herbrecht
General Hospital St-Jan, Brugge, Belgium.
Achiel
A
Van Hoof
Celgene Corporation, Summit, NJ, USA.
Lei
L
Zhang
Celgene Corporation, Summit, NJ, USA.
Sherri
S
Cicero
Celgene Corporation, Summit, NJ, USA.
Tommy
T
Fu
Mayo Clinic, Rochester, MN, USA.
Thomas
T
Witzig
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D000077269:Lenalidomide; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D013792:Thalidomide; D000077269:Lenalidomide
Ki-67; efficacy; lenalidomide; mantle cell lymphoma; safety