Комбинация Nivo-DHAP с последующей высокодозной химиотерапией и трансплантацией аутологичных гемопоэтических стволовых клеток у пациентов с рецидивами и рефрактерным течением классической лимфомы Ходжкина: результаты многоцентрового проспективного клинического исследования (ClinicalTrials.gov, NCT04091490)

Abstract

Background. High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is currently regarded as a standard treatment for patients with relapsed/refractory classical Hodgkin lymphoma (cHL). The efficacy of transplantation correlates with the depth of antitumor response achieved on pre-transplantation chemotherapy. A combination of PD-1 inhibitors with chemotherapy is a new forward-looking approach ensuring a higher rate of complete responses prior to auto-HSCT as well as better outcomes of the treatment in general. Aim. To assess the efficacy and safety of the combined program with Nivo-DHAP and subsequent HDCT and auto-HSCT in patients with relapsed/refractory cHL. Materials & Methods. From March 2020 to January 2022, 38 patients were enrolled in the study. The Nivo-DHAP program consisted of two stages. At stage 1 nivolumab immunotherapy was administered: two 240 mg/day IV infusions as a monoregimen 14 days apart. Stage 2, Nivo-DHAP immunochemotherapy, started in 14 days after stage 1: nivolumab 480 mg/day IV infusion on Day 1 in combination with DHAP chemotherapy, total of 4 cycles. The efficacy of this therapy was evaluated after 2 nivolumab infusions as well as after 2 and 4 Nivo-DHAP cycles. The program was fully implemented in 36 patients. HSCs were collected after remission had been reported, in most cases it was after 2 Nivo-DHAP cycles. For various reasons, auto-HSCT was performed only in 23 out of 36 patients. The median follow-up of patients after auto-HSCT was 24 months. Results. After completing the pre-transplantation stage of the program to the full extent, which included Nivo, Nivo, and 4 Nivo-DHAP cycles, 36 patients showed a 100 % overall objective response. Complete response was achieved in 27 (75 %) patients, and partial response was reported in 9 (25 %) patients. The signs of hematological toxicity grade 3/4 were manifested in 26 % of patients. In the total cohort of 36 patients with (n = 23) and without (n = 13) auto-HSCT, progression-free survival (PFS) was 81 % with the follow-up of 12 months, 78 % with the follow-up of 24 months, and 74 % with the follow-up of 36 months. Overall survival (OS) in the total cohort with the same follow-up end-points was 95 %. A comparative assessment revealed that PFS was 87 % in the cohort with auto-HSCT with the follow-up of 12, 24, and 36 months and 70 %, 64 %, and 48 % in the cohort without auto-HSCT with the same follow-up end-points, respectively (p = 0.056). Conclusion. A combination of PD-1 inhibitors with chemotherapy as a stage prior to HDCT followed by auto-HSCT is a promising strategy resulting in high PFS and OS rates. Preliminary data on using PD-1 inhibitors combined with chemotherapy cannot yet provide substantial basis for disregarding HDCT with subsequent auto-HSCT which is considered to be the optimal method for remission consolidation.