Bendamustine Monotherapy Is Effective As Salvage Therapy in Patients with Refractory / Relapsed Pediatric Hodgkin Lymphoma (HL): A Retrospective Analysis

Introduction: Despite high initial success rates in the treatment of pediatric HL, nearly 20% of patients develop resistant / relapsed disease. While high-dose chemotherapy with autologous stem cell transplantation has improved outcomes, the best of these regimens still have limited success rates and also such therapies are not easily available for most patients in Low and Middle Income Countries (LMICs). Novel therapeutic agents are needed in this setting. Bendamustine is an alkylating agent with clinical activity against various adult lymphomas, including limited data supporting its use in heavily pretreated adult HL patients. There is no such data in pediatric HL patients. Here we retrospectively report the results of single agent bendamustine salvage regimen in pediatric patients with refractory/relapsed HL.

Methods: Retrospective analysis of children with relapsed / refractory HL, who underwent treatment from January 2013 to February 2015, was performed. These patients, who were ineligible for autologous stem cell transplantation (ASCT) or had relapsed after ASCT (1), received bendamustine 120 mg/m² as a 30 minutes infusion on days 1 and 2 every 28 days with growth factor support. Total 6 cycles were planned for each patient. Early response was evaluated using PET-CT following 2 cycles of bendamustine and best response was evaluated post completion of 6 cycles of bendamustine.

Results: Of the 10 patients who were started on bendamustine, 8 received at least 2 cycles of bendamustine and were evaluable for response assessment. Of the 8, 7 were males and 1 female; median age was 13.5 years (range 5 to 15 years); the histology was mixed cellularity in 5 (62%) & nodular sclerosis in 3 (38%). Patients had received a median of 3 prior treatments (range 1 to 5). 5 had relapsed HL and 3 had primary progressive disease.

On evaluation for early PET-CT response post 2 cycles of bendamustine, 4 patients (50%) had Complete Remission (CR) and 4 patients (50%) had Partial Remission (PR) with an Overall Response Rate (ORR) of 100%. One patient with PR post 2 cycles underwent haploidential allo-SCT and later died of sepsis. The remaining 7 patients went on to receive 6 cycles of bendamustine, 6 of them (85%) achieved CR and continue to be in CR. 1 patient who was in PR was started on lenalidomide plus celecoxib maintenance and died of sepsis at home post chicken pox infection at 7 months. The median follow-up for all 8 patients is 15 months (range 6 to 24 months).

In general the treatment was well tolerated and toxicities, both hematological (grade II thrombocytopenia in 2 and febrile neutropenia in 1 patient) and extra-hematological were manageable.

Conclusions: Within the limits of an observational retrospective study, these data indicates that bendamustine shows its efficacy in patients with relapsed/refractory HL, without any significant toxicity. It produces durable responses in patients with relapsed/refractory HL and may be an effective bridge to further therapeutic interventions. It may also be used earlier in the treatment strategy of HL and in combination with other active drugs.