High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in the Third- and Subsequent-Line Therapy for Relapsed/Refractory Classical Hodgkin Lymphoma

BACKGROUND. High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) remains to this day the standard treatment for patients with a first relapse and/or refractory classical Hodgkin lymphoma (r/r cHL). However, in Russia in a real-world setting, this therapeutic procedure, for this or that reason, is often left to subsequent therapy lines.

AIM. To assess the efficacy and safety of HDCT with auto-HSCT in the third- and subsequent-line therapy for r/r cHL.

MATERIALS & METHODS. This study enrolled 90 r/r cHL patients treated at the NI Pirogov National Medical and Surgical Center from November 2019 to December 2024. The key enrollment eligibility criterion was the administration of PD-1 inhibitor as a monoregimen or combined with chemotherapy to achieve remission prior to auto-HSCT. The median age of patients was 36 years (range 19–56 years). In 48.9 % (n = 44) of cases, primary refractory disease was reported. The median number of prior therapy lines was 2 (range 2–7). PD-1 inhibitor as a monoregimen was administered directly prior to auto-HSCT to 53.3 % (n = 48) of patients, whereas 46.7 % (n = 42) of patients received it in combination with various chemotherapy protocols. BeEAC (n = 62; 68.9 %) and BEAM (n = 28; 31.1 %) were used as conditioning regimens.

RESULTS. Prior to auto-HSCT, overall objective response was achieved in 95.6 % (n = 86) of patients (complete response in 82.3 % and partial response in 13.3 % of patients). According to the LYRIC response criteria, 4.4 % (n = 4) of patients showed indeterminate response. Generally, early hematologic toxicity of the high-dose stage was similar to the complications observed after auto-HSCT in the treatment of lymphoproliferative diseases. It is worth noting that in 9 (10 %) patients, clinical and laboratory signs of autotransplant engraftment syndrome as well as relatively high cardiac toxicity (grade 3–5 in 8.9 % of patients; n = 8) were reported, if BeEAC was administered as conditioning regimen. With the follow-up median of 31 months, the 2-year progression-free survival was 79 % and overall survival was 90 %. During the follow-up period, 9 (10 %) relapses were registered, 8/9 within the first year after auto-HSCT.

CONCLUSION. HDCT with auto-HSCT in the third- and subsequent-line therapy for cHL patients with antitumor response to PD-1 inhibitors is a relatively safe and effective method. However, currently, there is not enough evidence to plan a shift of auto-HSCT to the third line due to the potential risk of the toxicity burden increasing after the prior therapy.

• Vladislav Olegovich Sarzhevskiy NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0001-7164-6595 (unauthenticated)
• Yu.V. Protopopova NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0001-8960-6241 (unauthenticated)
• N.E. Mochkin NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0001-5622-0828 (unauthenticated)
• E.A. Demina NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0002-0318-9051 (unauthenticated)
• A.A. Mamedova NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0002-7296-9190 (unauthenticated)
• A.A. Samoylova NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0002-3876-3869 (unauthenticated)
• V.S. Bogatyrev NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0001-6061-9428 (unauthenticated)
• A.A. Rukavisyn NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0002-5027-6932 (unauthenticated)
• E.G. Smirnova NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0003-1114-2592 (unauthenticated)
• N.S. Shorokhov NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0003-4442-289X (unauthenticated)
• A.E. Bannikova NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0003-3697-6876 (unauthenticated)
• V.Ya. Melnichenko NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203 https://orcid.org/0000-0002-6728-6264 (unauthenticated)

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