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.

Goy A., Kalayoglu Besisik S., Drach J., Ramchandren R., Robertson M. J., Avivi I., ...Daha Fazla

British journal of haematology, cilt.170, sa.4, ss.496-503, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 170 Sayı: 4
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1111/bjh.13456
  • Dergi Adı: British journal of haematology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.496-503
  • Anahtar Kelimeler: efficacy, Ki-67, lenalidomide, mantle cell lymphoma, safety, SINGLE-AGENT LENALIDOMIDE, PHASE-II, PROGNOSTIC INDEX, BORTEZOMIB, RITUXIMAB, MONOTHERAPY, MCL
  • İstanbul Üniversitesi Adresli: Evet

Özet

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 166, 40 and 209months, 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.