Phase I/II trial of bendamustine, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma. Blood Cancer J 2019 Jul 29;9(8):56
Date
07/31/2019Pubmed ID
31358733Pubmed Central ID
PMC6663939DOI
10.1038/s41408-019-0219-3Scopus ID
2-s2.0-85069933026 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
In this phase I/II trial, BID, bendamustine (70, 80, or 90 mg/m2), ixazomib (4 mg), and dexamethasone (40 mg), was administered to 28 patients with relapsed and/or refractory multiple myeloma (RRMM) exposed to bortezomib and lenalidomide and refractory to at least one. A 3 + 3 dose escalation based on dose-limiting toxicities (DLTs) was employed in phase I (total 15); 2/6 patients developed DLTs (neutropenia and thrombocytopenia) at dose level 3 establishing the recommended phase II dose as bendamustine 80 mg/m2, ixazomib 4 mg, and dexamethasone 40 mg. The median age was 67 years (range, 42-72), and 43% were females. Patients received a median of 4 (range, 4-9) prior lines of therapy, of which ~50% were double refractory. In phase II, total 19 patients were treated. With a median follow-up of 17 months, 11% achieved very good partial response, 50% achieved partial response, and 27% achieved stable disease. Median progression free (PFS) and overall (OS) survival were 5.2 months (95% CI, 1.96-8.3) and 23.2 months (95% CI 16.3-30.07). The most frequent adverse events were anemia, thrombocytopenia, leukopenia, nausea, diarrhea, and infections. Peripheral neuropathy was infrequent. BID is a well-tolerated and effective combination therapy for patients with RRMM.
Author List
Dhakal B, D'Souza A, Hamadani M, Arce-Lara C, Schroeder K, Chhabra S, Shah NN, Gauger K, Keaton T, Pasquini M, Hari PAuthors
Anita D'Souza MD Associate Professor in the Medicine department at Medical College of WisconsinBinod Dhakal MD Associate Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAged
Antineoplastic Combined Chemotherapy Protocols
Bendamustine Hydrochloride
Boron Compounds
Dexamethasone
Drug Resistance, Neoplasm
Female
Glycine
Humans
Male
Middle Aged
Multiple Myeloma
Neoplasm Recurrence, Local
Patient Safety
Treatment Outcome
