PO-06. Immune checkpoint inhibitors in pediatric Hodgkin lymphoma
Sabina V. Ryabenko, Andrey V. Kozlov, Asmik G. Gevorgyan, Ilya V. Kazantsev, Natalya B. Mikhailova, Ludmila S. Zubarovskaya
RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
Contact: Dr. Sabina V. Ryabenko, phone: +7 (911) 799-91-21, e-mail: firstname.lastname@example.org
While classical Hodgkin ‘s lymphoma is considered a curable disease and 80% of patients retain stable remission after first-line therapy, approximately 15% of them are primary refractory or develop relapse. Immune checkpoint inhibitors (ICIs) are effective in adults with Hodgkin’s lymphoma (HL), but there are only small pediatric groups described. Pembrolizumab and nivolumab are class IgG4 monoclonal antibodies to programmed death receptor 1 (PD-1). They selectively block interactions between PD-1 and its ligands PD-L1 and PD-L2, which restores the T-cells’ ability to recognize and destroy tumor cells. This study was aimed to evaluate the efficacy and safety of ICIs monotherapy in children and adolescents with relapsed or refractory HL.
Materials and methods
A total of 23 patients received monotherapy with nivolumab, and 2 patients with pembrolizumab. The median age was 15 (7-18) years. The HL morphologic variants were nodular sclerosis (n=20, 80%), HL with mixed cellularity (n=4, 16%), and HL with lymphocytes predominance (n=1, 4%). At the disease onset B-symptoms were registered in 14 (56%) patients, bulky disease (>7 cm) and extranodal lesions in 9 (36%) and 11 (44%) children, respectively. In 15 (60%) cases disease was primary refractory and in 10 (40%) the therapy was given at relapse. The median number of prior therapy lines was 3 (2-7). At treatment initiation 20 (80%) patients had disease progression, 4 (16%) partial response, and 1 (4%) stabilization according to the Lugano criteria. Nivolumab was given at dose of 3 mg/kg biweekly in 11 (48%) patients and as a single 40 mg dose every two weeks in 12 (52%) cases. Pembrolizumab was administered at a dose of 2 mg/kg every 3 weeks. Both drugs were given on outpatient basis. The median number of nivolumab injections was 8 (3-24). The response to the therapy was assessed according to LYRIC criteria. Upon ICIs course completion 11 patients received autologous and 1 allogeneic hematopoietic stem cell transplantation. In 2 (8%) cases, radiation therapy was used as consolidation.
The overall response rate to one observed in adult patients and reached 88% (complete in 40% and partial in 48% of cases). With a median follow-up of 940 (107-2311) days all patients were alive, but PFS at 1, 2, and 3 years was 66%, 49%, and 24%, respectively. However, as patients responded to subsequent therapy, 15 (60%) are currently alive and in remission. Clinically significant complications (autoimmune thyroiditis and tuberculosis) were noted in 2(8%) patients. In case of thyroiditis it was effectively controlled by steroids and ICIs were then reinitiated. In case with tuberculosis the ICIs therapy was interrupted.
Checkpoint inhibitor therapy allows achieving response in the majority of children with primary refractory or relapsed Hodgkin lymphoma. However, as the response is then lost in most cases, some form of consolidation (e.g. autologous HSCT) may be recommended.
Сhildren, Hodgkin’s lymphoma, refractory and relapsed disease, immune checkpoint inhibitors.