Combo is preferentially active in T-cell lymphomas
LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.
In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.
“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.
Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.
The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.
The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.
Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.
The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.
“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”
“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”
Treatment
Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.
Romidepsin doses ranged from 10 mg/m2 to 14 mg/m2. The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.
There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m2 on days 8 and 15 every 21 days.
There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m2 on days 8, 15, and 22 every 35 days.
Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m2 on days 8, 15, and 22 every 35 days.
Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.
Safety
Treatment-emergent adverse events occurring in at least 5% of patients included:
- Anemia—3% grade 3
- Anorexia—9% grade 1
- Back pain—6% grade 2
- Constipation—6% grade 1
- Cough—9% grade 1
- Depression—3% grade 1 and 2
- Diarrhea—15% grade 1 and 6% grade 2
- Dyspnea—3% grade 1 and 2
- Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
- Febrile neutropenia—3% grade 3 and 4
- Fever—6% grade 1 and 3% grade 2
- General disorders and administration site conditions—15% grade 1
- Hyperglycemia—3% grade 3
- Hypokalemia—6% grade 1
- Hypotension—3% grade 3
- Insomnia—6% grade 1
- Oral mucositis—9% grade 1 and 3% grade 2
- Nausea—18% grade 1, 27% grade 2, and 3% grade 3
- Neutrophil count decrease—3% grade 3 and 4
- Pain—3% grade 1 and 6% grade 2
- Pain of skin—3% grade 1 and 2
- Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
- Urinary tract infection—3% grade 3
- Vomiting—18% grade 1 and 21% grade 2.
