Combination orelabrutinib and sintilimab can produce rapid responses in patients with relapsed or refractory primary central nervous system lymphoma (PCNSL), according to research presented at the EHA 2022 Hybrid Congress.

Most patients achieved a response after 4 cycles of treatment, and none had relapsed at a median follow-up of 7 months.

This single-arm, phase 2 trial ( Identifier: NCT04899427) has enrolled 13 patients with relapsed/refractory PCNSL. The median age at baseline was 61 years (range, 48 to 71 years), and 7 patients were women.

Continue Reading

Most patients (n=11) had received 1 or 2 prior lines of therapy. All 13 patients had received high-dose methotrexate, 10 had received lenalidomide, 2 had prior whole-brain radiotherapy, and 7 were refractory to their last treatment.

The patients received orelabrutinib (150 mg once daily) in combination with sintilimab (200 mg on day 1 of each cycle) every 3 weeks per cycle. Patients are set to continue with treatment until disease progression, intolerable toxicity, death, or the 2-year mark.

The primary objective was the overall response rate (ORR) after 4 cycles of treatment. Ten patients completed 4 cycles, and 3 patients stopped treatment after the first 2 cycles due to disease progression.

The median follow-up was 7.0 months. At cycle 2, the ORR was 50%, and the complete response (CR) rate was 20%.

At cycle 4, the ORR was 61.5%, and the CR rate was 38.5%. The ORR and CR rate remained the same at cycle 6. The median time to response was 6 weeks (range, 6-12 weeks).

There were no relapses in patients who achieved an ORR at cycle 4. The estimated 1-year progression-free survival rate was 67.7%, and the 1-year overall survival rate was 92.3%.

The most common adverse events of any grade were fatigue (n=6), upper respiratory tract infection (n=6), neutropenia (n=4), and rash (n=3). There was 1 grade 3 adverse event —  Pneumocystis jirovecii pneumonia — and there were no grade 4 adverse events.

The treatment was well tolerated and induced rapid responses, said study presenter Yan Zhang, MD, of Peking Union Medical College Hospital in Beijing. However, the synergistic effects of BTK inhibition and PD-1 inhibition should be evaluated in additional studies of PCNSL, he added.

Disclosures: This research was supported by Innocare Pharma, Innovent, and CAMS Innovation Fund for Medical Sciences.


Zhang Y, Wang W, Zhao D, Zhang W, Zhou D. Preliminary results of a phase II study of orelabrutinib in combination with anti-PD-1 monoclonal antibody in refractory or relapsed primary CNS lymphoma. Presented at EHA 2022; June 9-12, 2022. Abstract S224.