ISSN 1866-8836
Клеточная терапия и трансплантация

LY-07. Immunochemotherapy with nivolumab, bendamustine, gemcitabine and rituximab (BeGeRN) in relapsed or refractory B-cell Non-Hodgkin Lymphoma: NCT03259529

Olesya G. Smykova, Vladislav V. Markelov, Kirill V. Lepik, Elena V. Kondakova, Lilia V. Stelmakh, Ivan S. Moiseev, Natalia B. Mikhailova, Alexander D. Kulagin

RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia

Contact: Dr. Olesya G. Smykova, phone: +7 (981) 144-67-95, e-mail:

doi 10.18620/ctt-1866-8836-2022-11-3-1-132


There are only limited treatment options for the patients with relapsed/refractory B-cell Non-Hodgkin Lymphoma (r/r NHL). Tumor cells may exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated efficacy and safety of programmed cell death-1 blockade by nivolumab combined with bendamustine, gemcitabine and rituximab (BeGeRN) in the patients with r/r NHL.

Patients and methods

This prospective study included 42 patients with r/r NHL, among them 52.4% (n=22) with diffuse large B-cell lymphoma (DLBCL); 35.7% (n=15) with primary mediastinal B-cell lymphoma (PMBCL) and 11.9% (n=5) with follicular lymphoma grade 3 (FL). Their median age was 42 (range, 18 to 66) years. Most patients (76.2%, n=32) had a primary chemoresistant disease. The median number of prior therapies was 3 (range, 2-6) lines. Ann Arbor stage III-IV was established in 69% patients (n=29), and bulky disease was documented in 35.7% of cases (n=15). Six patients (14.3%) underwent autologous stem cell transplantation prior to BeGeRN treatment. Median number of BeGeRN cycles was 2 (range, 1-4).


At median follow-up of 20.4 months (range, 2-60), the overall response rate (ORR) in the total group of patients was 41% (n=17), with complete response (CR) in 21% (n=9), and partial response (PR) in 20% of cases (n=8). Median duration of response for all patients with ORR (n=17) was 6.5 months (range: 0.8-59). The ORR value in patients with DLBCL was 45.5% (CR 18.1%), being 40% in PMBCL patients (CR 20%), and with ORR of 75% in the patients with FL (CR 50%). ORR in the patients with bulky disease was 33.3% (CR 20%) compared to ORR of 59.3% (CR 22.2%) in the patients without bulky disease. Four patients who achieved objective clinical response to the therapy underwent hematopoietic stem cell transplantation (auto-HSCT n=2, allo-HSCT n=2). Two patients who received auto-HSCT developed a relapse, and both patients after allo-HSCT remained in CR (up to 60 and 58 months). Three patients with BeGeRN failure received CAR-T cell therapy, and four patients were treated with glofitamab. Two-year overall survival and progression-free survival were 30% and 16%, respectively. Most common adverse events (grade 3-4) were associated with hematological toxicities: anemia, neutropenia, and thrombocytopenia developed in 22%, 62% and 37% patients, respectively. Non-hematologic toxicities grade 3-4 included febrile neutropenia in 36%, autoimmune cytopenia in 2% and Stevens-Johnson syndrome (response to glucocorticosteroids) was observed in 2% of patients.


Immunochemotherapy with nivolumab, bendamustine, gemcitabine and rituximab has a manageable toxicity profile and may lead to objective clinical response in the patients with r/r NHL. However, durability of the response to therapy is not long, and consolidation therapy is required, e.g., allo-HSCT, CAR-T, bispecific antibodies.


B-cell non-Hodgkin lymphoma, immunochemotherapy, nivolumab.

Volume 11, Number 3

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doi 10.18620/ctt-1866-8836-2022-11-3-1-132

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