Efficacy and safety of nivolumab combinations in patients with relapsed or refractory classical Hodgkin lymphoma
Polina V. Kotselyabina, Natalya B. Mikhailova, Kirill V. Lepik, Elena V. Kondakova, Andrey V. Kozlov, Yury R. Zalyalov, Marina O. Popova, Eugeniya S. Borzenkova, Ivan S. Moiseev, Vadim V. Baykov, Boris V. Afanasyev
Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
Contact: Dr. Polina V. Kotselyabina
E-mail: jewelpoulina@gmail.com
Summary
Therapy with immune checkpoint inhibitors had shown significant activity in patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL). However, disease relapse or progression is later observed in the majority of patients. One potential approach to enhance the effect of anti-PD1 therapy is a combination with chemotherapy and targeted therapy.
The aim of this analysis was to evaluate the safety and the efficacy of nivolumab (nivo) in combination(nivo) with bendamustine (benda), vinblastine (vin) and brentuximab vedotine (BV) in patients with relapsed r/r cHL after failure of nivo monotherapy.
Patients and methods
This analysis included 3 groups of adult patients. History and clinical status of the patients at the moment of combination therapy were summarized (Table 1) and evaluated according to LYRIC criteria. The first group (n=42) received nivo and benda. Patients were treated in a 28-day cycle for up to 3 cycles. Benda (90 mg/m2) was infused on day 1.2, and nivo (3 mg/kg) on day 1 of the cycle. The second group (n=16) received nivo and vin. The patients were treated in a 14-day cycle for up to 3 cycles. Vin (10 mg/m2) was infused on day 1, 2, and nivo (3 mg/kg), on day 1 of the cycle. The third group (n=11) received nivo and BV. Patients were treated in a 28-day cycle for up to 3 cycles. BV (1.8 mg/m2) was infused on day 1, and nivo (3 mg/kg) was administered on day 1 and14 of the cycle. Toxicity was graded according to the NCI CTCAE (version 4.03). After treatment completion, the clinical responses were evaluated by PET-CT scan and assessed by investigators using LYRIC criteria.
Results
Median follow-up time for first group (nivo/benda) was 24 months (8-33) from the start of the combined treatment. Median OS was not reached, 40/42 (95%) of patients were alive at the time of analysis. Median PFS was 10.6 months (7-14) with 31% of patients alive and free of disease progression (Table 2). Adverse events (AE) during treatment were observed in 40 (95%) of patients. The most common AE were fatigue (74%), nausea (64%), dyspnea (38%). Grade 3-4 adverse events included of severe fatigue, leukopenia, thrombocytopenia, uveitis, colitis, pneumonia, infusion reaction in 1 case each. All cases of immune related AE resolved completely after treatment with glucocorticosteroids. Median follow-up time for second group (nivo/vin) was 13 months (7-16) from the start of combined treatment. All the patients were alive at the time of the follow-up evaluation. Median PFS was 10 months (1-16), 38% of patients free of disease progression. AE during treatment were observed in 12 (75%) of patients. The most common AE were fatigue (63%), nausea (38%) and pruritus (38%). Grade 3-4 AE included of pneumonia in 1 case. Median follow-up time for first group (nivo/bv) was 27 months (10-30) from the start of combined treatment. At the time of analysis 10/11 (91%) of patients were alive. Median PFS was 12 months (4-30), 45% of patients free of disease progression. AE during treatment were observed in 8 (73%) of patients. The most common AEs were creatinine increase (55%), nausea (27%), fatigue (18%). Grade 3-4 AE included 2 cases of anemia and thrombocytopenia, and leukopenia in 1 case.
Conclusions
The results of analysis demonstrate that the nivolumab combinations have promising activity in the treatment of r/r cHL with a manageable toxicity profile.
Keywords
Hodgkin’s lymphoma, classical, PD-1, salvage treatment.
Table 1. Clinical characteristics of the patients treated with nivolumab
Note: PR, partial response; IR, indeterminate response; SD, stable disease; PD, disease progression
Table 2. Results of nivolumab-based therapy in Hodgkin’s disease
Note: OS, objective response; CR, complete response; PR, partial response; IR, indeterminate response;
SD, stable disease; PD, disease progression.