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Combined immunochemotherapy in patients with refractory/relapsed classical Hodgkin's lymphoma as a 2nd line treatment before autologous hematopoietic stem cell transplantation (preliminary results)

https://doi.org/10.17650/1818-8346-2022-17-3-40-47

Abstract

Aim. To study the efficacy and safety of combined immunochemotherapy according to the DHAp protocol + nivolumab in patients with refractory/relapsed classical Hodgkin's lymphoma before autologous hematopoietic stem cell transplantation.

Materials and methods. The study consisted of 2 phases: 1st - immunotherapy with nivolumab (2 injections as monotherapy at a dose of 240 mg/day with 14 days interval); 2nd - combined immunochemotherapy according to the DHAp protocol + nivolumab (14 days after the 2nd administration of nivolumab): nivolumab 480 mg/day on day 1 in combination with chemotherapy according to the DHAp protocol, 4 cycles in total. The effectiveness of therapy was evaluated after 2 injections of nivolumab, after 2 and 4 cycles of combination therapy. from March 2020 to November 2021, 32 patients were included in the study. The median age was 34 (18-55) years.

Results. As of November 2021, the result was evaluated in 32 patients after the 1st stage of treatment (nivolumab monotherapy). A complete response was obtained in 4 (12.5 %) patients, a partial response in 20 (62.5 %) patients, disease stabilization was noted in 5 (16 %) patients, an indeterminate response in 3 (9 %) patients. At the 2nd phase, the efficacy after the 2nd cycle of DHAp + nivolumab was evaluated in 31 patients (complete response was obtained in 19 (61 %), partial response in 11 (36 %)); the final efficacy evaluation (after the 4th cycle of DHAp + nivolumab) was performed in 30 patients, and all patients achieved response to therapy (complete response in 25 (83 %), partial response in 5 (17 %)). 2 patients were excluded from the study.

Conclusion. preliminary results of combined immuno- and chemotherapy according to the DHAp protocol showed high efficacy and relatively low toxicity in patients with refractory/relapsed classical Hodgkin's lymphoma before autologous hematopoietic stem cell transplantation.

About the Authors

A. A. Mamedova
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

Ajsel' A. Mamedova.

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



N. E. Mochkin
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



V. O. Sarzhevskiy
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



E. A. Demina
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



V. S. Bogatyrev
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



A. A. Spornik
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



A. A. Samoylova
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



A. A. Rukavitsin
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



E. G. Smirnova
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



A. E. Bannikova
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



V. Ya. Melnichenko
N.I. Pirogov National Medical and Surgical Center, Ministry of Health of Russia
Russian Federation

70 Nizhnyaya Pervomayskaya St., Moscow 105203.



N. B. Mikhaylova
Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, Ministry of Health of Russia
Russian Federation

12 Rentgena St., Saint-Petersburg 197022.



E. S. Borzenkova
Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, Ministry of Health of Russia
Russian Federation

12 Rentgena St., Saint-Petersburg 197022.



L. V. Stelmakh
Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, Ministry of Health of Russia
Russian Federation

12 Rentgena St., Saint-Petersburg 197022.



Yu. R. Zalyalov
Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, Ministry of Health of Russia
Russian Federation

12 Rentgena St., Saint-Petersburg 197022.



A. A. Semenova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.



G. S. Tumyan
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.



M. A. Danilova
National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

4 Koroleva St., Obninsk 249031.



O. A. Konova
National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

4 Koroleva St., Obninsk 249031.



N. A. Falaleeva
National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

4 Koroleva St., Obninsk 249031.



A. Yu. Terekhova
National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

4 Koroleva St., Obninsk 249031.



M. A. Vernyuk
P.A. Hertzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284.



A. M. Chervontseva
P.A. Hertzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284.



L. S. Khayrullina
P.A. Hertzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284.



A. A. Maslov
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037.



I. B. Lysenko
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037.



Yu. A. Alekseeva
V.A. Almazov National Medical Research Centre, Ministry of Health of Russia
Russian Federation

8 Akkuratova St., Saint-Petersburg 197341.



E. S. Pavlyuchenko
I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation

47 Piskarevskiy Prospekt, Saint-Petersburg 195067.



A. A. Mirsaitov
I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation

47 Piskarevskiy Prospekt, Saint-Petersburg 195067.



A. A. Zverkova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.



I. V. Ishmatova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.



S. A. Volchenkov
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.



M. S. Motalkina
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.



I. S. Zyuzgin
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.



References

1. Russian clinical guidelines for the diagnosis and treatment of lymphoproliferative diseases. Eds.: I.V. Poddubnaya, V.G. Savchenko. Moscow, 2018. Pp. 28-38. (In Russ.)]

2. Demina E.A. Hodgkin's lymphoma. Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika = Clinical oncohematology. Basic Research and Clinical Practice 2015;8(4):463-70. (In Russ.).

3. Skoetz N., Trelle S., Rancea M. et al. Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: a systematic review and network meta-analysis. Lancet Oncol 2013;14(10):943-52. DOI: 10.1016/S1470-2045(13)70341-3

4. Kuruvilla J., Keating A., Crump M. How I treat relapsed and refractory Hodgkin lymphoma. Blood 2011;117(16):4208-17. DOI: 10.1182/blood-2010-09-288373

5. Mohty R., Dulery R., Bazarbachi A.H. et al. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J 2021;11(7):126. DOI: 10.1038/s41408-021-00518-z

6. Mochkin N.E., Sarzhevskii V.O., Dubinina Yu.N. et al. Outcome of classical Hodgkin's lymphoma treatment based on high-dose chemotherapy and autologous hematopoietic stem cell transplantation: the experience in the N.I. Pirogov Russian National Medical Center of Surgery. Klinicheskaya onkogematologiya = Clinical Oncohematology 2018;11(3):234-40. (In Russ.). DOI: 10.21320/2500-2139-2018-11-3234-240

7. Schmitz N., Pfistner B., Sextro М. et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet 2002;359(9323):2065-71. DOI: 10.1016/S0140-6736(02)08938-9

8. Aparicio J., Segura A., Garcera S. et al. ESHAP is an active regimen for relapsing Hodgkin's disease. Ann Oncol 1999;10(5):593-5. DOI: 10.1023/a:1026454831340

9. Josting A., Rudolph C., Reiser M. et al. Time-intensified dexamethasone/ cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Ann Oncol 2002;13(10):1628-35. DOI: 10.1093/annonc/mdf221

10. Moskowitz C.H., Nimer S.D., Zelenetz A.D. et al. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood 2001;97(3):616-23. DOI: 10.1182/blood.v97.3.616

11. Santoro A., Magagnoli M., Spina M. et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica 2007;92(1):35-41. DOI: 10.3324/haematol.10661

12. Baetz T., Belch A., Couban S. et al. Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 2003;14(12):1762-7. DOI: 10.1093/annonc/mdg496

13. Armand P., Engert A., Younes A. et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 Trial. J Clin Oncol 2018;36(14):1428-39. DOI: 10.1200/JCO.2017.76.0793

14. Chen R., Zinzani P.L., Fanale M.A. et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 2017;35(19):2125-32. DOI: 10.1200/JCO.2016.72.1316

15. Ansell S.M., Lesokhin A.M., Borrello I. et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015;372(4): 311-9. DOI: 10.1056/NEJMoa1411087

16. Armand P. Immune checkpoint blockade in hematologic malignancies. Blood 2015;125(22):3393-400. DOI: 10.1182/blood-2015-02-567453

17. Sarzhevskii V.O., Demina E.A., Mochkin N.E. et al. Checkpoint inhibitors and classical Hodgkin's lymphoma: efficacy and safety of pembrolizumab in relapsed/refractory tumor (experience at the N.I. Pirogov Russian National Medical Center of Surgery). Klinicheskaya onkogematologiya = Clinical Oncohematology 2021;14(1):53-62. (In Russ.). DOI: 10.21320/2500-2139-2021-14-1-53-62

18. Herrera A.F., Chen R., Palmer J. et al. PET-adapted Nivolumab +/- ICE (NICE) as first salvage therapy in relapsed or refractory Hodgkin lymphoma. Hematol Oncol 2019. DOI: 10.1002/hon.102_2630

19. Moskowitz A.J., Shah G., Schoder H. et al. Phase II trial of pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy for relapsed or refractory classical Hodgkin lymphoma. J Clin Oncol 2021;39(28):3109-17. DOI: 10.1200/JCO.21.01056


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For citations:


Mamedova A.A., Mochkin N.E., Sarzhevskiy V.O., Demina E.A., Bogatyrev V.S., Spornik A.A., Samoylova A.A., Rukavitsin A.A., Smirnova E.G., Bannikova A.E., Melnichenko V.Ya., Mikhaylova N.B., Borzenkova E.S., Stelmakh L.V., Zalyalov Yu.R., Semenova A.A., Tumyan G.S., Danilova M.A., Konova O.A., Falaleeva N.A., Terekhova A.Yu., Vernyuk M.A., Chervontseva A.M., Khayrullina L.S., Maslov A.A., Lysenko I.B., Alekseeva Yu.A., Pavlyuchenko E.S., Mirsaitov A.A., Zverkova A.A., Ishmatova I.V., Volchenkov S.A., Motalkina M.S., Zyuzgin I.S. Combined immunochemotherapy in patients with refractory/relapsed classical Hodgkin's lymphoma as a 2nd line treatment before autologous hematopoietic stem cell transplantation (preliminary results). Oncohematology. 2022;17(3):40-47. (In Russ.) https://doi.org/10.17650/1818-8346-2022-17-3-40-47

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ISSN 1818-8346 (Print)
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