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Phase I trial of bortezomib in combination with rituximab‐HyperCVAD alternating with rituximab, methotrexate and cytarabine for untreated aggressive mantle cell lymphoma
Author(s) -
Romaguera Jorge E.,
Fayad Luis E.,
McLaughlin Peter,
Pro Barbara,
Rodriguez Alma,
Wang Michael,
Weaver Pamela,
Hartig Kimberly,
Kwak Larry W.,
Feldman Tatyana,
Smith Judy,
Ford Peggy,
Goldberg Stuart,
Pecora Andrew,
Goy Andre
Publication year - 2010
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/j.1365-2141.2010.08315.x
Subject(s) - bortezomib , medicine , rituximab , cytarabine , mantle cell lymphoma , regimen , vincristine , cyclophosphamide , oncology , multiple myeloma , gastroenterology , surgery , chemotherapy , lymphoma
Summary Mantle cell lymphoma (MCL) outcomes have improved over the last two decades; however, late relapses occur. Bortezomib has shown single agent activity of 33% in relapsed MCL and has an additive/synergistic effect in vitro when combined with drugs currently used to treat MCL. We hypothesized that a combination of bortezomib with current intense non‐transplant chemoimmunotherapy might prevent late relapses. The toxicity of bortezomib when combined with methotrexate and cytarabine is unknown. Patients aged 18–79 years with untreated aggressive MCL were treated with R‐HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) alternating with rituximab‐methotrexate/cytarabine (R‐M/A). Bortezomib was added to the R‐Hyper‐CVAD combination as a fixed dose of 1·3 mg/m 2 IV on days 2 and 5 and was added to the R‐M/A regimen after rituximab, in increasing doses of 0·7, 1, and 1·3 mg/m 2 in cohorts of three patients. Twenty patients were assessed for toxicity of the regimen. The principal toxicity was haematological and did not differ from that observed with a similar regimen without the bortezomib. In particular, there was no pulmonary or neurological dose‐limiting toxicity, showing that bortezomib can be safely combined with R‐HyperCVAD and R‐M/A.