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Bortezomib, low‐dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma
Author(s) -
Popat Rakesh,
Oakervee Heather,
Williams Catherine,
Cook Mark,
Craddock Charles,
Basu Supratik,
Singer Charles,
Harding Stephen,
Foot Nicola,
Hallam Simon,
Odeh Liz,
Joel Simon,
Cavenagh Jamie
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.1365-2141.2008.07572.x
Subject(s) - bortezomib , medicine , melphalan , multiple myeloma , neutropenia , dexamethasone , regimen , adverse effect , gastroenterology , surgery , chemotherapy
Summary This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1·3 mg/m 2 on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2·5–10·0 mg/m 2 ) on day 2 of a 28‐day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty‐three patients were enrolled. The MTD was defined at melphalan 7·5 mg/m 2 and bortezomib 1·3 mg/m 2 . The overall response rate (ORR) was 68% (23% complete or near‐complete responses [CR/nCR]) whilst at the MTD ( n = 33) the ORR was 76% (34% CR/nCR). After median follow‐up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD ( P < 0·05 vs. non‐MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low‐dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.