Treatment of patients with central nervous system lymphoma
Daniil I. Shmidt, Andrey N. Gavrilenko, Alexey Y. Polushin, Elena V. Kondakova, Kirill V. Lepik, Nadezhda V. Medvedeva, Anna V. Klimovich, Yury R. Zalyalov, Natalia B. Mikhailova, Boris V. Afanasyev
Pavlov First Saint Petersburg State Medical University, State Clinical Hospital №31, St. Petersburg, Russia
Contact: Dr. Daniil I.Schmidt
Primary (PCNSL) and secondary (SCNSL) central nervous system lymphoma still carry a poor prognosis. Treatment of relapsed/refractory (r/r) CNS lymphoma remains a challenge. Biological features of CNS lymphoma determine the opportunity to use checkpoint inhibitors in r/r CNS lymphoma. Our aim was to analyze our clinical experience with these patients.
Patients and methods
Retrospective analysis included 35 patients (pts) with CNS lymphoma treated at the First Pavlov Saint Petersburg State medical University between 2010 and 2019. SCNSL comprised 54% of patients (n=19), PCNSL – 40% (n=14), and 6% (n=2) had CNS involvement in primary testicular lymphoma (PTL). Latter would further be analysed together with PCNSL due to shared biological and clinical characteristics. Median age at a diagnosis was 56 (30-65) in pts with PCNSL and 48 (20-65) in pts with SCNSL. Tumor histology was diffuse large B-cell lymphoma in 83% of cases. Relapsed or refractory CNS lymphoma was the case in 21 pts (60%): PCNSL, 81% (n=13/16); SCNSL, 42% (n=8/19). Nivolumab (nivo) was used in 12 pts: in PCNSL, 44% (n=7/16); SCNSL, 26% (n=5/19). Median follow-up was 16 months (mo) (0-99): 24.5 mo (0-99) for PCNSL, and 12 mo (1-34) for SCNSL pts. One patient had been infected with HIV prior to SCNSL diagnosis.
The lesions affected brain parenchyma in 23 pts (14 with PCNSL and 9 with SCNSL), meningeal layers in 7 pts (1 PTL, 6 SCNSL), the both structures were affected in 5 cases (1 PCNSL, 4 SCNSL). Deep structures were involved in 19 pts (11 PCNSL, 8 SCNSL), and 17 pts had multiple lesions (9 PCNSL, 8 SCNSL. Treatment-related mortality was 11% (n=4/35). One-year overall survival (OS) was 74% in PCNSL, and 69% in SCNSL group. Six-months OS in r/r disease was 75% for PCNSL, and 33% for SCNSL. The patients received nivolumab at the doses of 3 mg/kg (n=3), 1 mg/kg (n=6), 100 mg (n=3) и 200 mg (n=1). Median follow-up in the pts receiving nivo was 7 mo (0-31). Objective response rate was 58% (n=7). Complete response was seen in 6 pts (3 PCNSL, 3 SCNSL), partial response – in 1 PCNSL patient, 4 pts had stable disease (2 PCNSL, 2 SCNSL). The disease progression was the case in 1 patient with PCNSL. Nivo was tolerated well. Grade 2 adverse events (AE) were observed, i.e., immune arthritis and maculopapular rash. No severe AE (grade 3-4) were registered. Eight patients who received nivolumab are alive at the moment of data evaluation. Tumor resection was performed in 8 (23%) pts (6 with PCNSL, and 2, with SCNSL). Consolidation took place in 11 (31%) pts (4 PCNSL, 7 SCNSL). Radiation therapy was performed in 11 pts (31%): 5 PCNSL, 4 SCNSL. Autologous hematopoietic stem cell transplant was performed in 1 patient with PCNSL and 5 pts with SCNSL.
Suboptimal number of pts receives consolidation therapy. Nivolumab therapy is a safe and efficient option in some pts with primary and secondary CNS lymphoma pts. Appropriateness, timing and optimal regimen of nivolumab treatment should be determined in prospective trials.
Lymphoma, central nervous system, primary, secondary, nivolumab, therapy.