Nivolumab monotherapy in childhood refractory and relapsed Hodgkin’s lymphoma

Introduction Immune checkpoint inhibitors (ICIs) demonstrate substantial efficiency in Hodgkin’s lymphoma (HL). Pembrolizumab was approved for the treatment of children with HL, but the role of other ICIs in pediatrics should only to be elucidated.

Methods Thirteen children and adolescents with refractory and relapsed(R-R) HL received nivolumab (nivo) monotherapy in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Pavlov First St. Petersburg State Medical University. Median age was 17 years (11 to 18). Histological forms of HL were as follows: nodular sclerosis was diagnosed in 11 patients (84.6%); mixed cellularity HL, 1 case (7.7%) and nodular lymphocyte predominant Hodgkin’s lymphoma, 1 (7.7%). Median number of previous therapy lines was 4 (2-7) with autologous hematopoietic stem cell transplantation (HSCT) in 5 cases (38.5%). Prior to nivo therapy, 10 children (77%) had progression; 1 (7.7%), stabilization, and 2 (15.3%), partial remission according to Lugano criteria. Treatment schedule consisted of 3 mg/kg of nivo biweekly in 8 (61.5%) or 40 mg of nivo biweekly in 5 (38.5%). Median number of nivo cycles was 10 (5-24). Response to treatment was evaluated by the LYRIC criteria.

Results Nivo resulted in overall response of 92% (12 patients); complete response, in 61.5% (8), partial response, in 30.8% of cases (4) and indeterminate response, in 7.7% (1). Three-year overall survival (OS) was 100%. Progression free survival (PFS) rates according to Kaplan-Meier method at 1, 2 and 3 years were 80.8%, 69.3% and 34.6%, respectively. With median follow-up of 447 days (91-1137) nine patients (69.2%) remained in remission state. Median PFS was 30 months. Complications of nivo were registered in 1 adolescent (7.7%). This patient developed autoimmune thyroiditis which required hormone replacement therapy. It didn’t lead to discontinuation of the drug. We did not observe any unacceptable toxicity of nivo.

Conclusion Nivo is effective in the majority of children and adolescents with R-R HL. However, many patients relapse after treatment. Therefore, it is important to improve the results by shifting to combination therapy, incorporation of ICIs earlier in treatment and consolidation with HSCT. Nivo is relatively safe with only one clinically significant adverse effect (autoimmune thyroiditis) observed in our study.