Pembrolizumab plus vorinostat induces response in subset of patients with Hodgkin lymphoma
Click Here to Manage Email Alerts
The combination of pembrolizumab and vorinostat demonstrated efficacy among patients with relapsed or refractory Hodgkin lymphoma, according to phase 2 study results presented at ASH Annual Meeting and Exposition.
Those who benefited from the combination included patients who had previously experienced disease progression on PD-1 blockade.
“Even though PD-1 blockade is effective in patients with Hodgkin lymphoma, a minority of patients achieve complete response and the curative potential of anti-PD-1 monotherapy is relatively low,” Alex F. Herrera, MD, assistant professor in the department of hematology and hematopoietic cell transplantation at City of Hope Medical Center, told Healio. “Additionally, patients with Hodgkin lymphoma who are refractory to PD-1 blockade have limited treatment options, and effective treatments for these patients is an important unmet need. There are preclinical data that demonstrate histone deacetylase inhibition can have immunomodulatory effects and can synergize with PD-1 blockade in a range of tumor types.”
The study included 32 patients (median age, 35 years; 69% men; 72% white) with relapsed or refractory Hodgkin lymphoma who failed at least one prior line of therapy and were ineligible to undergo transplant. The majority (75%) of patients had stage III to stage IV disease. Median number of prior therapies was four (range, 2-12).
Patients received treatment in a dose-escalation cohort with two dose levels. For dose-level one, two patients received 100 mg oral vorinostat (Zolinza, Merck), a histone deacetylase inhibitor, on days 1 to 5 and 8 to 12. For dose-level two, 30 patients received 200 mg vorinostat on days 1 to 5 and 8 to 12. All patients also received pembrolizumab (Keytruda, Merck), an anti-PD-1 antibody, dosed at 200 mg every 3 weeks. Treatment continued for up to 2 years.
Safety and determination of the phase 2 dose served as the primary endpoints.
Among 30 evaluable patients, researchers observed a best overall response rate of 73% and a complete response rate of 33%. The 14 anti-PD-1-naive/sensitive patients demonstrated an ORR of 93% and complete response rate of 64%. Among the 18 patients who were refractory to prior PD-1 blockade, the ORR was 56% and complete response rate was 6%.
Median follow-up was 18 months among the 28 surviving patients. Median duration of response was 14 months, median PFS was 14.9 months and median OS had not yet been reached. Researchers reported a 1-year PFS rate of 52% and 1-year OS rate of 93%.
Common any-grade adverse events included hypertension (72%), fatigue (63%), hyponatremia (63%), nausea (63%), diarrhea (47%), thrombocytopenia (44%) and anemia (41%). The most common grade 3 or higher adverse events included hypertension (9%), neutropenia (6%), thrombocytopenia (6%), hypophosphatemia (6%) and lymphopenia (6%).
Twenty patients discontinued treatment due to disease progression (n = 11), stem cell transplant (n = 6), patient’s preference (n = 2) and 2-year treatment completion (n = 1).
“Our study shows that combination therapies may resensitize patients with Hodgkin lymphoma to PD-1 blockade and allow for patients to continue benefiting from immunotherapy,” Herrera said.
Collapse
Herrera AF, et al. Abstract 234. Presented at: ASH Annual Meeting and Exposition; Dec. 11-14, 2021; Atlanta.
Read more about
Click Here to Manage Email Alerts