Combination pembrolizumab and vorinostat may induce a response in some patients with relapsed or refractory B-cell lymphomas, particularly primary mediastinal B cell lymphoma (PMBCL), according to an analysis from a phase 1 trial published in Haematologica. Other non-Hodgkin lymphoma (NHL) subtypes, however, did not show a high overall response rate.
Immunotherapies including PD-1 inhibitors, such as pembrolizumab, have not been shown to drastically improve outcomes in previous lymphoma trials. Although response rates are approximately 50% among patients with PMBCL, few patients have a complete response (CR), and among those who do not, progressive disease is common.
Previous evidence suggests that histone deacetylase inhibitors, such as vorinostat, may have immunomodulating effects that work synergistically with PD-1 inhibition. For this phase 1 study (ClinicalTrials.gov Identifier: NCT03150329), researchers are evaluating the safety and efficacy of combination pembrolizumab and vorinostat among patients with relapsed or refractory lymphoma. For the present paper, researchers analyzed data from patients with NHL, and gave data from the dose-escalation cohort.
Two dose levels (DLs; DL1: 100 mg; DL2: 200 mg) of vorinostat were administered to 6 patients each over a 3-week cycle. A dose-limiting toxicity was noted for both DL1 and DL2: at DL1, 1 patient had a case of Stevens-Johnson syndrome that led to death after intervention and at DL2, 1 patient had a thromboembolism. The researchers set DL2 as the recommended phase 2 dose.
Overall, among patients with NHL, 11 patients with diffuse large B-cell lymphoma (DLBCL) were enrolled and treated, among whom 5 had PMBCL; 9 patients had follicular lymphoma (FL). Among patients with DLBCL, the median age was 51 years, 45% were male sex, and 9% of patients had double-hit disease. Among patients with FL, the median age was 60 years, 89% of patients were male sex, and 100% of patients had double refractory disease.
The median numbers of treatment cycles in the FL, non-PMBCL DLBCL, and PMBCL groups were 4, 3, and 32, respectively. Analysis showed that, in the FL, non-PMBCL DLBCL, and PMBCL groups, the CR rates were 11%, 17%, and 80%, while the partial response rates were 11%, 17%, and 0%.
The median duration of response was not reached for any patient with DLBCL. Median overall survival was not reached for any subgroup in the population. Grade 3 or worse adverse events noted in at least 10% of patients included neutrophil count decrease (15%) and lymphocyte count decrease (10%).
“Particularly high rates of durable CRs in [PMBCL] support further investigation of this treatment regimen in this specific patient population (both in the PD-1 naïve and PD-1 refractory settings),” the authors wrote in their report.
Godfrey J, Mei M, Chen L, et al. Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin. Haematologica. Published online July 20, 2023. doi:10.3324/haematol.2023.283002