Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma

Jonas Paludo, Joseph R Mikhael, Betsy R. Laplant, Alese E. Halvorson, Shaji K Kumar, Morie Gertz, Suzanne R. Hayman, Francis K. Buadi, Angela Dispenzieri, John A. Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David M Dingli, Ronald S. Go, Yi Lin, Wilson Gonsalves, Rafael Fonseca, Peter Leif Bergsagel, Vivek RoyTaimur Sher, Asher A Chanan Khan, Sikander Ailawadhi, Alexander Keith Stewart, Craig B. Reeder, Paul G. Richardson, S Vincent Rajkumar, Martha Lacy

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

This phase 1/2 trial evaluated the maximum tolerated doses, safety, and efficacy of pomalidomide, bortezomib, and dexamethasone (PVD) combination in patients with relapsed lenalidomide-refractory multiple myeloma (MM). In phase 1, dose level 1 consisted of pomalidomide (4 mg by mouth on days 1 to 21), IV or subcutaneous bortezomib (1.0 mg/m2 on days 1, 8, 15, and 22), and dexamethasone (40 mg by mouth on days 1, 8, 15, and 22) given every 28 days. Bortezomib was increased to 1.3 mg/m2 for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients. Objective response rate was 86% (95% confidence interval [CI], 73-94) among all evaluable patients (stringent complete response, 12%; complete response, 10%; very good partial response, 28%; and partial response, 36%) and 100% among high-risk patients. Within a median follow-up of 42 months, 20% remain progression free, 66% are alive, and 4% remain on treatment. Median progression-free survival was 13.7 months (95% CI, 9.6-17.7). The most common toxicities were neutropenia (96%), leukopenia (84%), thrombocytopenia (82%), anemia (74%), and fatigue (72%); however, the majority of these were grade 1 or 2. The most common grade ≥3 toxicities included neutropenia (70%), leukopenia (36%), and lymphopenia (20%). Deep vein thrombosis occurred in 5 patients. In conclusion, PVD is a highly effective combination in lenalidomide-refractory MM patients. Weekly administration of bortezomib enhanced tolerability and convenience. Toxicities are manageable, mostly consisting of mild cytopenias with no significant neuropathy. This trial was registered at www.clinicaltrials.gov as #NCT01212952.

Original languageEnglish (US)
Pages (from-to)1198-1204
Number of pages7
JournalBlood
Volume130
Issue number10
DOIs
StatePublished - Sep 7 2017

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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