The use of immunotherapy for the treatment of refractory forms of Hodgkin lymphoma in real clinical practice.

With a frequency of 2.2 cases per 100,000 population in Russia, Hodgkin's lymphoma (HL) is one of the most common malignant neoplasms in young people. In connection with the predominant spread of HL among young people, the issue of effective treatment of various forms of HL remains relevant. Currently, 70-90 % of patients with HL who have received standard chemotherapy or chemoradiotherapy have a long period of remission. However, 10 % of patients with progressive course, can`t achieve a response, and 30 % of patients subsequently recur. The standard approach of treating recurrent and/or refractory HL after initial treatment is “salvage therapy” followed by consolidation with high-dose chemotherapy and stem cell transplantation. Although there is a model for treating these patients, recent research has focused on improving the effectiveness and tolerability of rescue therapy. The use of anti- PD-1 drugs opens up new possibilities for the treatment of recurrent/refractory HL. The article describes the results of using checkpoint inhibitors for patients with a history of multi- course chemotherapy. Inhibitors of immune check points were supplemented in the 3rd and subsequent lines of ChT. A clinical case with immunotherapy supplementation in a patient with severe comorbidity is also presented.

1. Russian clinical guidelines for the diagnosis and treatment of malignant lymphoproliferative diseases. Ed. by Demina EA, Poddubnaya IV, Savchenko VG. General principles of lympho ma diagnosis. 2018, 470 p. (In Russian).

2. Malignant neoplasms in Russia in 2017 (morbidity and mortality). Ed. by A.D.Kaprin, V.V.Starinsky, G.V.Petrova. Moscow: P.A.Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, 2018, 250 p. (In Russian).

3. Baryakh E.A. treatment of relapse and refractory Hodgkin lymphoma. Oncohematology. 2017;12(2):8–13. (In Russian). https://doi.org/10.17650/1818-8346-2017-12-2-8-13

4. Steidl C, Connors JM, Gascoyne RD. Molecular pathogenesis of Hodgkin’s lymphoma: increasing evidence of the importance of the microenvironment. J Clin Oncol. 2011 May 10;29(14):1812–1826. https://doi.org/10.1200/JCO.2010.32.8401

5. Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin. 2018 Mar;68(2):116–132. https://doi.org/10.3322/caac.21438

6. Yudin DI, Laktionov KK, Sarantseva KA, Breder VV, Reuto va EV, Borisova OI, et al. Pseudoprogression in patients on immunotherapy. Medical Council. 2019;(10):10-14. (In Russ.) https://doi.org/10.21518/2079-701X-2019-10-10-14

7. Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, et al. Long-Term Follow-Up of Contemporary Treatment in Early-Stage Hodgkin Lymphoma: Updated Analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 Trials. J Clin Oncol. 2017 Jun 20;35(18):1999–2007. https://doi.org/10.1200/JCO.2016.70.9410

8. Schmitz N, Pfi stner B, Sextro M, Sieber M, Carella AM, Haenel M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemo sensitive Hodgkin’s disease: a randomised trial. Lancet. 2002 Jun 15;359(9323):2065–2071. https://doi.org/10.1016/S0140-6736(02)08938-9

9. Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, et al. Reduced-intensity chemotherapy and PET-guided radio therapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012 May 12;379(9828):1791–1799. https://doi.org/10.1016/S0140-6736(11)61940-5

10. Voorhees TJ, Beaven AW. Therapeutic Updates for Re lapsed and Refractory Classical Hodgkin Lymphoma. Cancers (Basel). 2020 Oct 8;12(10):2887. https://doi.org/10.3390/cancers12102887

11. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183–2189. https://doi.org/10.1200/JCO.2011.38.0410

12. Bekoz, H, Ozbalak M, Karadurmus N, Paydas S, Turker A, Toptas T, et al. Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. Ann Hematol. 2020 Nov;99(11):2565–2576. https://doi.org/10.1007/s00277-020-04077-4

13. Patent for the invention RU 2487727 C1, 20.07.2013. Application No. 2012106961/14 on 27.02.2012. Kit OI, Sne zhko TA, Lysenko IB, Ushakova ND, Zlatnik EYu. Method of treatment of patients with refractory and recurrent Hodgkin's lymphoma.