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Long term results of a phase 2 study of vincristine sulfate liposome injection ( M arqibo ® ) substituted for non‐liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non‐ H odgkin lymphomas
Author(s) -
Hagemeister Fredrick,
Rodriguez Maria Alma,
Deitcher Steven R.,
Younes Anas,
Fayad Luis,
Goy Andre,
Dang Nam H.,
Forman Arthur,
McLaughlin Peter,
Medeiros Leonard Jeffrey,
Pro Barbara,
Romaguera Jorge,
Samaniego Felipe,
Silverman Jeffrey A.,
Sarris Andreas,
Cabanillas Fernando
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12446
Subject(s) - vincristine , prednisone , cyclophosphamide , liposome , medicine , doxorubicin , pharmacology , chemotherapy , chemistry , biochemistry
Summary Vincristine sulfate liposome injection ( VSLI ; M arqibo ® ; M ) is active in relapsed and refractory lymphomas, and approved in the U nited S tates 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‐ H odgkin 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 10·2 years, respectively. The 5‐ and 10‐year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35 mg, 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.