Phase 2 study of clarithromycin, pomalidomide, and dexamethasone in relapsed or refractory multiple myeloma

Abstract

The addition of clarithromycin enhances the efficacy of lenalidomide plus dexamethasone in treatment-naive multiple myeloma (MM). We conducted a phase 2 trial to evaluate the safety and efficacy of clarithromycin, pomalidomide, and dexamethasone (ClaPd) in relapsed or refractory multiple myeloma (RRMM) with prior lenalidomide exposure. One hundred twenty patients with a median of 5 prior lines of therapy received clarithromycin 500 mg orally twice daily, pomalidomide 4 mg orally on days 1 to 21, and dexamethasone 40 mg orally on days 1, 8, 15, and 22 of a 28-day cycle. The overall response rate (ORR) was 60% with 23% achieving at least a very good partial response. There was no statistical difference in response rates for patients who were refractory to lenalidomide (ORR, 58%), bortezomib (ORR, 55%), or both lenalidomide and bortezomib (ORR, 54%). Median progression-free survival (PFS) for the cohort was 7.7 months and median overall survival (OS) was 19.2 months. A history of dual-refractoriness to lenalidomide and bortezomib did not significantly impact either PFS or OS. The most common toxicities were neutropenia (83%), lymphopenia (74%), and thrombocytopenia (71%). The most common grade ≥3 toxicities included neutropenia (58%), thrombocytopenia (31%), and anemia (28%). ClaPd is an effective combination in RRMM with response and survival outcomes that are independent of lenalidomide- or bortezomib-refractory status. Toxicities are manageable with low rates of nonhematologic or high-grade events. ClaPd is a convenient, all-oral option in RRMM with comparable efficacy to other highly active, 3-drug, pomalidomide-based combinations. This trial was registered at www.clinicaltrials.gov as #NCT01159574.

Conflict of interest statement

Conflict-of-interest disclosure: T.M.M. provided consultation services for Amgen Inc, Takeda Inc, Celgene Inc, and Janssen. A.C.R. received honoraria for speakers’ bureau activities from Celgene Inc. K.A.P. and A.P. received honoraria for speakers’ bureau activities from Celgene Inc and Takeda Inc. M.C. received honoraria for speakers’ bureau activities from, was an advisory board member for, and received research funding from Celgene Inc and Takeda Inc. R.N. received honoraria for speakers’ bureau activities from, was an advisory board member for, and received research funding from Celgene Inc, Takeda Inc, and Onyx Inc. The remaining authors declare no competing financial interests.

© 2019 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Responses over time to ClaPD. Responses by treatment cycle in patients who were lenalidomide refractory (A), bortezomib refractory (B), and refractory to both lenalidomide and bortezomib (double refractory) (C).

Figure 2.

Survival outcomes. (A) PFS. Median PFS was 7.67 months (95% CI, 5.6, 9.5). (B) OS. Median OS was 19.2 months (95% CI, 14.2, 26.7).