LY-01. Nivolumab-based salvage therapy for relapsing Hodgkin lymphoma after allogeneic stem cell transplantation

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated for the patients with relapsed and refractory classical Hodgkin lymphoma (r/rHL) due to its potential to be cured. While long-term disease control can be achieved by this approach, disease relapse still remains the factor limiting the success of transplantation. Immune checkpoint inhibitors (ICIs) showed encouraging efficiency in patients with rrHL with benign toxicity profile. Intensification the graft vs lymphoma effect by checkpoint inhibitors is an attractive option, although there are concerns about the risks of nivolumab treatment after allo-HSCT due to the risk of severe GVHD, thus the place of ICIs is not yet defined. This report includes the results of treatment with nivolumab or combined regimens in patients with relapse or progression cHL after allo-HSCT.

Patients and methods

We retrospectively evaluated efficacy and toxicity of nivolumab-based treatment in 10 patients with r/rHL relapsing or progression after allo-HSCT at the RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University. Most of the patients (n= 6, 60%) received reduced intensity conditioning: fludarabine 30 mg/m², bendamustine 130 mg/m² per day for 3 days (FluBe) regimen. Post-transplant cyclophosphamide-based GvHD prophylaxis was used for 7 patients (70%). Objective response determined as complete response (CR) or partial response (PR) before allo-HSCT was documented in 7 (70%) patients (6, CR, 60%, 1, PR, 10%) and 3 patients (30%) received transplant during the disease progression (PD). Matched HLA-related siblings and matched unrelated donors were used in 6 (60%) and 4 patients (40%) respectively. All the patients have received the treatment with brentuximab vedotin (BV) as salvage therapy after allo-HSCT, six of them received combination of BV with bendamustine. Six patients received donor lymphocyte infusions before nivolumab initiation. All the patients for the treatment of relapse/progression of cHL were initiated nivolumab therapy as monotherapy at various doses (from 0.5 to 3 mg/kg body weight), administered every 2 weeks. Before nivolumab therapy, 8 and 5 patients had a history of aGVHD and cGVHD, respectively. Median time from allo-HSCT to disease relapse/progression was 3.3 months (1.5-16.5). Median time from disease relapse/progression to first injection of nivolumab was 28.9 months (range 5-42.4).

Results

At the median follow up of 29 month (12-46 mo), 9 patients were alive. The median overall survival (OS) was not reached, and OS was 90% at 46 mo. The median progression-free survival (PFS) was 40 months (21-46 mo) and PFS was 40%. All the patients achieved оbjective response (CR in 50%, and PR in 50%) after a median of 6 (1-6) nivolumab injections. At the median of 6.7 months (5 to 8.5), 6 patients relapsed and received retreatment with nivolumab (n=5), or switched to pembrolizumab (n=1). Due to the achieved disease control, five patients required additional chemotherapy. An objective response was achieved in 3 out of 6 patients with combination therapy. None of the patients developed extensive GVHD after nivolumab administration. During nivolumab treatment, 3 (30%) of the patients experienced grade 3-4 adverse events, which included two cases of aseptic meningitis, and one case of аutoimmune hepatitis, autoimmune hypophysitis. Due to severe adverse events, the nivolumab treatment was discontinued, and patients received short courses of glucocorticoids with complete resolution of the event. In this analysis, there was no correlation between dose of nivolumab and response rate, incidence and severity of adverse events.

Conclusion

Nivolumab as monotherapy or in combination with cytotoxic agents showed promising efficacy in patients with BV-refractory relapse of HL after allo-HSCT. The immune-mediated toxicities and the potential for GVHD exacerbation remain an important issue.

Keywords

Hodgkin’s lymphoma, resistant, nivolumab, efficiency, adverse effects.