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Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non‐Hodgkin lymphoma
Author(s) -
Barr Paul M.,
Fu Pingfu,
Lazarus Hillard M.,
Horvath Nancy,
Gerson Stanton L.,
Koc Omer N.,
Bahlis Nizar J.,
Snell Michael R.,
Dowlati Afshin,
Cooper Brenda W.
Publication year - 2009
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.1365-2141.2009.07836.x
Subject(s) - bortezomib , mantle cell lymphoma , fludarabine , medicine , rituximab , chronic lymphocytic leukemia , follicular lymphoma , lymphoma , regimen , oncology , aggressive lymphoma , gastroenterology , multiple myeloma , chemotherapy , leukemia , cyclophosphamide
Summary Based on the hypothesis that bortezomib may potentiate fludarabine activity by inhibiting DNA repair, we designed a phase I trial using this combination with rituximab in patients with relapsed and refractory indolent and mantle cell non‐Hodgkin lymphoma. Twenty‐four patients were enrolled. Non‐Hodgkin lymphoma subtypes included 12 patients with follicular lymphoma, four with marginal zone lymphoma, three with lymphoplasmacytic lymphoma, three with mantle cell lymphoma and two with small lymphocytic/chronic lymphocytic leukaemia. Fludarabine and bortezomib were escalated in cohorts of three patients. Rituximab was added to the maximum tolerated dose of fludarabine and bortezomib and added significant dose‐limiting myelosuppression. The maximum tolerated dose was fludarabine 25 mg/m 2 on days 1–3, bortezomib 1·3 mg/m 2 on days 1, 4, 8, 11, with rituximab 375 mg/m 2 on day 1 administered every 21 d. Clinical responses were observed in 11 patients, five of whom were refractory to their most recent treatment regimen. Six additional patients had stable disease for a median of 10 months (range 4–30+). Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL.