Bendamustine, lenalidomide, and dexamethasone (BRD) is highly effective with durable responses in relapsed multiple myeloma.
Bendamustine is a multifunctional alkylating agent with single agent activity in myeloma. We designed the current phase 1/2 trial to determine the maximum tolerated doses (MTD) of bendamustine that can be safely combined with lenalidomide and dexamethasone and to assess the safety and efficacy of the combination. Patients with relapsed MM following at least 1 prior therapy, but no more than four lines of prior therapy and with measurable disease were enrolled. Bendamustine 75 mg/m(2) given on days 1 and 2, lenalidomide 25 mg given days 1-21 and dexamethasone 40 mg on days 1, 8, 15, and 22, was the recommended Phase 2 dose. Seventy-one patients were accrued: 21 on Phase 1 and 50 on Phase 2. The median age was 62.3 years; patients had a median of three prior lines of therapy (range 1-4), with over 70% of the patients having received prior lenalidomide, bortezomib, and/or peripheral blood stem cell transplant. Thirty-four of 70 (49%) patients had a confirmed partial response or better, including 20 patients (29%) with a very good partial response or better. An additional 4 patients had a minor response, translating to an overall 55% clinical benefit rate. Grade 3 or higher toxicity was seen in 96% of patients, with ≥grade 3 hematologic in 94% and nonhematologic in 50%. The median progression free survival was 11.8 months and the median duration of response was 23 months. The combination of bendamustine, lenalidomide, and dexamethasone is very effective in relapsed multiple myeloma with high response rates and durable responses
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Shaji K
SK
Kumar
Division of Hematology, City of Hope, Duarte, California.
Amrita
A
Krishnan
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Betsy
B
LaPlant
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Kristina
K
Laumann
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida.
Vivek
V
Roy
Division of Hematology, Univerity of Chicago, Chicago, Illinois.
Todd
T
Zimmerman
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Morie A
MA
Gertz
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Francis K
FK
Buadi
Division of Hematology, Mayo Clinic, Rochester, Minnesota.|Division of Hematology, Washington University, St.Louis, Missouri.
Keith
K
Stockerl Goldstein
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Ann
A
Birgin
Division of Hematology, Washington University, St.Louis, Missouri.
Mark
M
Fiala
Division of Hematology, City of Hope, Duarte, California.
Lupe
L
Duarte
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida.
Michelle
M
Maharaj
Multiple Myeloma Research Consortium, Norwalk, Connecticut.
Joan
J
Levy
Division of Hematology, Washington University, St.Louis, Missouri.
Ravi
R
Vij
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D013792:Thalidomide; D003907:Dexamethasone; D000069461:Bendamustine Hydrochloride; D000077269:Lenalidomide