Duvelisib Plus Romidepsin Yields High Results in Relapsed/Refractory Peripheral T-Cell Lymphoma
A phase 1 dose-expansion trial (NCT02783625) found that utilizing duvelisib (Copiktra) plus romidepsin (Istodax; DR) for patients with relapsed/refractory peripheral T-cell lymphoma (PTL) resulted in high response efficacy, according to results presented at the 2021 American Society of Hematology Annual Meeting.
Efficacy-evaluable patients with relapsed/refractory PTCL treated with the maximum tolerated dose (MTD) of DR (n = 48) achieved an overall response rate (ORR) of 56%, including 21 (44%) patients with a complete response (CR). The combination also proved to be active in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL); among 9 efficacy-evaluable patients the ORR was 44%. The median progression-free survival (PFS) was 6.8 months (95% CI, 4.0-not reached [NR]) and 5.3 months (95% CI, 2.8-NR) in the PTCL and CTCL cohorts, respectively.
The trial employed a parallel 3 plus 3 design with patients in arm A (n = 59) receiving DR and patients in arm B receiving duvelisib plus bortezomib (Velcade) in the dose-escalation stage. Ten patients received a lead-in cycle with single agent duvelisib before the dose expansion phase at the MTD. The MTD of DR was previously determined to be intravenous romidepsin 10 mg/m2 plus 75 mg oral duvelisib twice daily.
The primary end point of the trial was to define the MTD and to characterize the safety and toxicity of DR and duvelisib plus bortezomib. Secondary objectives included ORR at the MTD, CR rate, partial response rate, time to response, duration of response, and event-free survival. The exploratory end points were correlation of response with prior therapy and tissue collection for further correlative predictors of response or resistance to therapy.
The objective of the PTCL expansion cohort was to show that DR is more effective than single agent romidepsin. In a phase 2 study (NCT00426764), treatment with romidepsin resulted in an ORR of 25% (CI 17.6%-32.4%) among 130 patients with relapsed/refractory PTCL. The targeted ORR for DR in the phase 1 trial was 50% to within plus/minus 15% with confidence intervals of 35%-65%.
Patients treated with the combination at the MTD (n = 59) had a median age of 64 (range, 20-81) and were predominately male (66%) and White (80%). The median number of prior lines of therapy was 3 (range, 1-16). Nineteen percent had prior transplants, including 15% previously receiving autologous stem cell transplantation and 3% previously receiving allogenic stem cell transplantation.
Among the 14 previously transplanted patients, the median PFS was NR (95% CI, 12.7-NR). These patients had a median age of 57 (range, 20-69), a median of 2 prior lines of therapy (range, 1-5), and were mostly male (71%).
In terms of safety, the rate of grade 3/4 transaminitis for all patients treated at the MTD was 14%, 40% in patients initiated with a single agent lead-in cycle (n = 10), and 8% in patients initiated with DR at MTD (n = 49). Other common grade 3/4 adverse events for patients initiated with the combination at the MTD included decreased neutrophil count (39%), diarrhea and infections (both 12%), decreased platelet count (10%), and rash (8%).
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