Pembrolizumab Plus Vorinostat Shows Tolerable Safety and Promising Responses for Patients With PD-1 Blockade Refractory Classical Hodgkin Lymphoma

According to findings from a phase 1 dose-expansion study published in Blood, a combination of pembrolizumab plus vorinostat exhibited tolerable safety and promising overall response rates among patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL), particularly among those refractory to programmed cell death protein-1 (PD-1) blockade. 

In this study, Matthew Mei, MD, City of Hope, Duarte, California, and coauthors aimed to assess the potential value of adding vorinostat to pembrolizumab to treat patients with relapsed/refractory (R/R) cHL, diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). The primary end point was safety and the establishment of a recommended phase 2 dose. 

A total of 32 patients with R/R cHL who had undergone ≥ 1 prior line of therapy and were unable to receive transplantation were included in this study. Among these patients, 78% received anti-PD-1 therapy, and 56% were PD-1 refractory. All patients were assigned to a dose-expansion cohort with 2 dose levels (DLs), followed by an expansion cohort at the determined recommended phase 2 dose in 21-day cycles. 

Patients received vorinostat at 100 mg twice daily (DL1) and 200 mg twice daily (DL2) from days 1 to 5 and 8 to 12. All patients were administered pembrolizumab at 200 mg every 3 weeks. 

Results indicated that patients experienced the following grade ≥ 3 adverse events: hypertension (9%), neutropenia (9%), hypophosphatemia (9%), thrombocytopenia (6%), and lymphopenia (6%). Patients experienced the following immune-related adverse events: grade 1 or 2 thyroiditis (13%), grade 1 rash (6%), and grade 3 esophagitis/duodenitis (3%). 

Patients achieved an overall response rate of 72% and a complete response rate of 34%. Among the 18 patients refractory to prior PD-1 blockade, the overall response was 56% and the complete response rate was 11%. 

Mei and study authors concluded, “Pembrolizumab and vorinostat was well-tolerated with a high ORR rate in R/R cHL, including in anti–PD-1–refractory disease.” 

Source: 

Mei M, Chen L, Godfrey J, et al. Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade. Blood. Published online: October 19, 2023. doi: 10.1182/blood.2023020485