Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo®) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas

Vincristine sulfate liposome injection (VSLI; Marqibo((R)); M) is active in relapsed and refractory lymphomas, and approved in the United States for relapsed and refractory adult acute lymphocytic leukaemia. We evaluated VSLI (2.0 mg/m(2) without dose cap) substituted for non-liposomal vincristine (VCR) in a cyclophosphamide, doxorubicin, vincristine, prednisone +/- ritiximab (CHOP +/- R) regimen, creating CHMP +/- R in 72 untreated, aggressive non-Hodgkin lymphoma patients, including 60 with diffuse large B-cell lymphoma (DLBCL). The overall response rate was 96% (69/72) including complete response (CR) in 65 (90%) and unconfirmed CR in 2 (3%). Median progression-free survival (PFS) and overall survival (OS) were not reached at median follow-up of 8 and 102years, respectively. The 5- and 10-year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35mg, the safety profile of CHMP +/- R was comparable to that reported for CHOP +/- R. Grade 3 peripheral neuropathy was reported in 2 (3%) patients; there was no reported Grade 3/4 constipation. CHMP +/- R was highly active, generally well tolerated, and compared favourably to historical trials with R-CHOP in DLBCL. This enhanced activity probably reflects VCR dose intensification, pharmacokinetic optimization, and enhanced delivery afforded by VSLI. A Phase 3 trial of R-CHMP versus R-CHOP in elderly patients with untreated DLBCL is ongoing.