ISSN (print) 1997-6933     ISSN (online) 2500-2139
Vol. 17 No. 1 (2024), CLINICAL TRIALS
Vol. 17 No. 1 (2024)
CLINICAL TRIALS

Nivo-DHAP Combined with Subsequent High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma: Results of a Multi-Center Prospective Clinical Trial (ClinicalTrials.gov, NCT04091490)

Published 17.05.2024
V.O. Sarzhevskii
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
Aisel Akifovna Mamedova
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
N.E. Mochkin
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
E.A. Demina
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
A.A. Spornik
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
A.A. Samoilova
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
V.S. Bogatyrev
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
A.A. Rukavitsyn
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
E.G. Smirnova
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
N.S. Shorokhov
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
A.E. Bannikova
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
V.Ya. Melnichenko
NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203
N.B. Mikhailova
RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022
E.S. Borzenkova
RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022
L.V. Stelmakh
RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022
Yu.R. Zalyalov
RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022
A.A. Semenova
NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478
G.S. Tumyan
NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478
M.A. Danilova
National Medical Research Center of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
O.A. Konova
National Medical Research Center of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
N.A. Falaleeva
National Medical Research Center of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
AYu Terekhova
National Medical Research Center of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
M.A. Vernyuk
PA Gertsen Moscow Oncology Research Institute, branch of the NMRC of Radiology, 3 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284
A.M. Chervontseva
PA Gertsen Moscow Oncology Research Institute, branch of the NMRC of Radiology, 3 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284
L.S. Khairullina
PA Gertsen Moscow Oncology Research Institute, branch of the NMRC of Radiology, 3 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284
A.A. Maslov
PA Gertsen Moscow Oncology Research Institute, branch of the NMRC of Radiology, 3 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284
I.B. Lysenko
National Medical Research Center for Oncology, 63 korp. 8 14th liniya ul., Rostov-on-Don, Russian Federation, 344037
Yu.A. Alekseeva
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
E.S. Pavlyuchenko
II Mechnikov North-Western State Medical University, 47 Piskarevskii pr-t, Saint Petersburg, Russian Federation, 195067
A.A. Mirsaitov
NN Petrov National Medical Cancer Research Center, 68 Leningradskaya ul., pos. Pesochnyi, Saint Petersburg, Russian Federation, 197758
A.A. Zverkova
NN Petrov National Medical Cancer Research Center, 68 Leningradskaya ul., pos. Pesochnyi, Saint Petersburg, Russian Federation, 197758
I.V. Ishmatova
NN Petrov National Medical Cancer Research Center, 68 Leningradskaya ul., pos. Pesochnyi, Saint Petersburg, Russian Federation, 197758
S.A. Volchenkov
NN Petrov National Medical Cancer Research Center, 68 Leningradskaya ul., pos. Pesochnyi, Saint Petersburg, Russian Federation, 197758
M.S. Motalkina
NN Petrov National Medical Cancer Research Center, 68 Leningradskaya ul., pos. Pesochnyi, Saint Petersburg, Russian Federation, 197758
I.S. Zyuzgin
NN Petrov National Medical Cancer Research Center, 68 Leningradskaya ul., pos. Pesochnyi, Saint Petersburg, Russian Federation, 197758
2024-1
PDF_2024-17-1_1-10 (Russian)

Keywords

classical Hodgkin lymphoma
nivolumab
immunotherapy
chemotherapy
autologous hematopoietic stem cell transplantation

How to Cite

Sarzhevskii V.O., Mamedova A.A., Mochkin N.E., Demina E.A., Spornik A.A., Samoilova A., Bogatyrev V.S., Rukavitsyn A.A., Smirnova E.G., Shorokhov N.S., Bannikova A.E., Melnichenko V.Y., Mikhailova N.B., Borzenkova E.S., Stelmakh L.V., Zalyalov Y.R., Semenova A.A., Tumyan G.S., Danilova M.A., Konova O.A., Falaleeva N.A., Terekhova A.Y., Vernyuk M.A., Chervontseva A.M., Khairullina L.S., Maslov A.A., Lysenko I.B., Alekseeva Y.A., Pavlyuchenko E.S., Mirsaitov A.A., Zverkova A.A., Ishmatova I.V., Volchenkov S.A., Motalkina M.S., Zyuzgin I.S. Nivo-DHAP Combined with Subsequent High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma: Results of a Multi-Center Prospective Clinical Trial (ClinicalTrials.gov, NCT04091490). Clinical Oncohematology. 2024;(1):1–10. doi:10.21320/2500-2139-2024-17-1-1-10.
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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.

PDF_2024-17-1_1-10 (Russian)

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