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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.
Tomer M. Mark, MD, of the University of Colorado at Denver, Aurora, and his colleagues, reported these results in Blood Advances.
The trial (NCT01159574) 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. Blood Adv. 2019 Feb 26;3(4):603-11.
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.
Tomer M. Mark, MD, of the University of Colorado at Denver, Aurora, and his colleagues, reported these results in Blood Advances.
The trial (NCT01159574) 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. Blood Adv. 2019 Feb 26;3(4):603-11.
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.
Tomer M. Mark, MD, of the University of Colorado at Denver, Aurora, and his colleagues, reported these results in Blood Advances.
The trial (NCT01159574) 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. Blood Adv. 2019 Feb 26;3(4):603-11.
FROM BLOOD ADVANCES