Combination pembrolizumab and rituximab produces a high overall response rate (ORR) in patients with relapsed or refractory follicular lymphoma (FL), but the durability of responses could be improved, according to researchers.

The team tested the combination in a phase 2 trial ( Identifier: NCT02446457) and reported their findings in Blood Advances.

The trial included 30 patients with rituximab-sensitive, relapsed/refractory FL. The patients’ median age was 64 years (range, 43-84 years), 57% were men, 87% had stage III-IV disease, and 50% had a high tumor burden. Patients had received a median of 1 (range, 1-4) prior treatment.

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Patients received pembrolizumab (200 mg IV) every 3 weeks for up to 16 cycles and rituximab (375 mg/m2 IV) every week for 4 weeks in cycle 1 only.

The ORR was 67%, which included 15 complete responses and 5 partial responses. The median duration of response was 17.5 months.

Patients with a high tumor burden had a lower ORR than those with a low tumor burden — 53% and 80%, respectively (P =.002). The ORR was also lower in patients whose disease had progressed within 24 months after first-line therapy compared with those whose disease had not progressed in that time — 36% and 84%, respectively (P =.04).

At a median follow-up of 34.9 months, 93% of patients were still alive, 23% were in remission, 77% had disease progression, and 7% had died from disease progression.

The median progression-free survival was 12.6 months, and the median overall survival was not reached. The 3-year overall survival rate was 97%.

The most common grade 3/4 adverse events were liver enzyme abnormalities (3%), diarrhea (3%), nausea (3%), vomiting (3%), aseptic meningitis (3%), and pancreatitis (3%). Grade 3/4 immune-related events occurred in 13% of patients. There were no treatment-related deaths.

The researchers concluded that pembrolizumab plus rituximab has a favorable safety profile and produces a high ORR.

“However, for this approach to be practice changing, improved durability of response is desirable,” they wrote. “Several approaches could be considered to enhance the durability, including extended dosing of rituximab instead of the single cycle of 4 weekly doses administered in this study, or combination approaches to enhance T-cell trafficking into the tumor and blocking of multiple immunosuppressive mechanisms in the tumor microenvironment.”

Disclosures: This research was partially supported by Merck. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Nastoupil LJ, Chin CK, Westin JR, et al. Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. Blood Adv. Published online February 14, 2022. doi:10.1182/bloodadvances.2021006240