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Pomalidomide, Bortezomib and Dexamethasone (PVD) for Patients with Relapsed, Lenalidomide Refractory Multiple Myeloma

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

Key points

  • PVD is an active combination in relapsed, lenalidomide refractory MM patients.

  • PVD with weekly bortezomib offers a simpler, more convenient and well tolerated regimen option.

Abstract

This phase I/II trial evaluated the maximum tolerated doses (MTD), safety and efficacy of pomalidomide, bortezomib and dexamethasone (PVD) combination in patients with relapsed, lenalidomide refractory, MM. In the phase I, dose level 1 consisted of pomalidomide 4mg PO days 1-21, bortezomib 1.0 mg/m2 IV or SQ days 1,8,15,22 and dexamethasone 40mg PO days 1,8,15,22 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. High-risk status by mSMART criteria was seen in 24% of patients. Median number of prior regimens was 2 (72% had stem cell transplant, 58% had bortezomib and 56% had alkylators). Objective response rate was 86% (95% CI:73-94) among all evaluable patients (sCR 12%, CR 10%, VGPR 28%, PR 36%) and 100% among high-risk patients. With median follow up of 42 months, 20% remain progression free, 66% are alive and 4% remain on treatment. The median PFS was 13.7 months (95%CI:9.6-17.7). The most common toxicities were neutropenia (96%), leukopenia (84%), thrombocytopenia (82%), anemia (74%), fatigue (72%); however, the majority of these were grade 1-2. The most common grade ≥3 toxicities included neutropenia (70%), leukopenia (36%), lymphopenia (20%). DVT occurred in five 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.

  • Submitted May 11, 2017.
  • Accepted June 21, 2017.