An all-oral, three-drug regimen may be a treatment option for relapsed or refractory multiple myeloma, according to researchers.
The regimen – clarithromycin, pomalidomide, and dexamethasone (ClaPd) – produced an overall response rate (ORR) of 60% in a phase 2 trial of patients with relapsed/refractory multiple myeloma (RRMM). Response rates were similar whether patients were refractory to lenalidomide, bortezomib, or both drugs.
The most common adverse events (AEs) in this trial were hematologic toxicities.
, of the University of Colorado at Denver, Aurora, and his colleagues, reported these results in
The trial () included 120 patients with RRMM. They had a median age of 63 years (range, 42-87 years) and were a median of 4.6 years (range, 0.8-21.2 years) from diagnosis at baseline.
The patients had received a median of 5 (range, 3-15) prior lines of therapy. Most patients were refractory to lenalidomide (n = 101), bortezomib (n = 94), or both (n = 81).
The ClaPd regimen consisted of clarithromycin given at 500 mg twice daily, pomalidomide at 4 mg on days 1-21, and dexamethasone at 40 mg on days 1, 8, 15, and 22 of a 28-day cycle. The patients received ClaPd until intolerance or disease progression. In addition to ClaPd, patients received thromboprophylaxis (aspirin at 81 mg daily) and Pneumocystis jiroveci prophylaxis (trimethoprim-sulfamethoxazole or an alternative).
The toxicities were manageable, with low rates of nonhematologic and high-grade events, according to the researchers. The most common grade 3 or higher AEs were lymphopenia (60%), neutropenia (58%), leukopenia (34%), thrombocytopenia (31%), and anemia (28%).
Among all evaluable patients, the ORR was 60% (70/117). One patient had a complete response, 6 had a stringent complete response, 20 had a very good partial response, and 43 had a partial response.
ORRs were similar whether patients were refractory to bortezomib, lenalidomide, or both. The ORR was 58% (n = 59) among lenalidomide-refractory patients, 55% (n = 52) among bortezomib-refractory patients, and 54% (n = 44) among double-refractory patients.
For the entire cohort, the median progression-free survival was 7.7 months and the median overall survival was 19.2 months.
In a multivariate analysis, there were two factors significantly associated with inferior overall survival – having a revised International Staging System score greater than 1 (hazard ratio, 2.75; P = .044) and having at least 5% of CD138 cells positive for Ki67 on immunohistochemistry (hazard ratio, 1.84, P = .030).
“The ClaPd regimen demonstrated high rates of overall response and significant duration of disease control in a heavily pretreated RRMM population while maintaining a toxicity profile similar to Pom-dex [pomalidone-dexamethasone] alone,” Dr. Mark and his colleagues wrote. “The clinical efficacy advantage of adding clarithromycin to Pom-dex should be explored further in a phase 3 clinical trial.”
This research was supported by Celgene; the Myeloma Center at Weill Cornell Medicine, New York; and a grant from the National Institutes of Health. Dr. Mark reported relationships with Amgen, Takeda, Celgene, and Janssen. Other study authors reported relationships with Celgene, Takeda, and Onyx Pharmaceuticals.
SOURCE: Mark TM et al. .