Lead author Pier Luigi Zinzani, MD: “In this ongoing trial, pembrolizumab achieved a treatment response rate of 41 percent, while median duration of response and median overall survival have not yet been met, [and] all responders were alive at data cutoff. These results are particularly impressive given that this patient population was heavily pretreated. While very few published studies have been conducted in this patient population, response rates in historic controls were considerably lower [than these results]. If these results are confirmed in larger, later-stage trials, pembrolizumab may offer rrPMBCL patients a potentially more effective treatment option. The potential survival benefits over existing treatments are particularly noteworthy.”
Patients with relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have limited treatment options and poor prognosis, but, according to interim results from the ongoing phase Ib KEYNOTE-013 trial, the anti-PD-1 antibody pembrolizumab could be a promising new agent for this patient population.
Pier Luigi Zinzani, MD, from the University of Bologna in Italy, and his co-authors reported interim results from the multicenter, international, multicohort, open-label trial, which enrolled adult patients with rrPMBCL (a disease associated with PD-L1 and PD-L2 overexpression) who had been failed by, were ineligible for, or refused autologous hematopoietic cell transplantation (HCT). Their findings were published in Blood.
Patients were eligible if they had an Eastern Cooperative Oncology Group performances status score of 0-1, had not received allogeneic HCT within the past 5 years, had no symptomatic central nervous system disease, and had no prior use of agents targeting T-cell co-stimulation or checkpoint pathways.
Eighteen patients (median age = 30 years; median lines of prior therapy = 3; 72% female) were included in the study. The first 11 patients received pembrolizumab 10 mg/kg IV every 2 weeks (one patient withdrew and was not dosed); after a study amendment, the subsequent eight patients received pembrolizumab 200 mg IV every 3 weeks. Treatment continued until disease progression, until unacceptable toxicity, or as long as 2 years.
Eleven patients (61%) experienced drug-related adverse events (AEs), the most common of which were hypothyroidism (n=2), nausea (n=2), fatigue (n=2), pyrexia (n=2), and decreased appetite (n=2). Grade 3/4 AEs included one grade 3 neutropenia and one grade 4 veno-occlusive liver disease subsequent to allogeneic HCT (which occurred after pembrolizumab was discontinued). No AEs resulted in patient death.
After a median follow-up of 11.3 months (range = 3.4-27.4 months), the overall response rate (ORR; primary endpoint) was 41 percent (n=7/17), with two patients achieving complete response (CR) and five achieving partial response (PR). Thirty-five percent of patients had stable disease as best response.
“The ORR [of 41%] was higher than reported in prior retrospective studies, where it ranged from 0 to 25 percent in patients who were primary-refractory to or had relapsed after anthracycline-based chemotherapy,” the authors wrote. “In our study, 81 percent (n=13/16) of patients evaluable by imaging had an overall decrease in target lesions, [and] in two of these patients, reductions were <5 percent.”
The median duration of response (DOR) was not reached, and the DORs in the two patients who achieved CR were 2.4 and 20.5 months, with response ongoing at the time of data cutoff (May 27, 2016).
Ten patients discontinued treatment due to progressive disease (n=9), or physician decision (n=1). Two patients achieving CR or PR reached the maximum 2 years of treatment duration before data cutoff and remain in remission. All patients who had an objective response to pembrolizumab were alive at data cutoff.
The study is limited by its small patient population and lack of a control group. “Additional clinical trials are required before recommendations can be made on whether pembrolizumab represents a new treatment option in PMBCL,” Dr. Zinzani told ASH Clinical News. “Given the rarity of rrPMBCL, randomized trials in this patient population are very difficult to conduct.”
Source: Zinzani PL, Ribrag V, Moskowitz CH, et al. Safety & tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017. [Epub ahead of print]