The Use of Checkpoint Inhibitors in Classical Hodgkin’s Lymphoma during the COVID-19 Pandemic (Pirogov Medical Center’s Experience)

VO Sarzhevskii, EA Demina, NE Mochkin, AA Spornik, AA Mamedova, EG Smirnova, AE Bannikova, AA Samoilova, VS Bogatyrev, OYu Bronov, YuA Abovich, VYa Melnichenko

NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Vladislav Olegovich Sarzhevskii, MD, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: +7(495)603-72-17; e-mail: vladsar100@gmail.com

For citation: Sarzhevskii VO, Demina EA, Mochkin NE, et al. The Use of Checkpoint Inhibitors in Classical Hodgkin’s Lymphoma during the COVID-19 Pandemic (Pirogov Medical Center’s Experience). Clinical oncohematology. 2020;13(3):307–15 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-307-315


ABSTRACT

Background. Currently, there are neither systematic data nor clinical guidelines for checkpoint inhibitor immunotherapy in cancer patients in the context of the COVID-19 pandemic. In this respect classical Hodgkin’s lymphoma (cHL) is no exception. The article deals with the experience of Pirogov Medical Center (NI Pirogov Russian National Medical Center of Surgery) in PD-1-inhibitor immunotherapy in relapsed/refractory cHL in the context of the COVID-19 pandemic. The authors endeavour to cover matters of current interest concerning immunotherapy and differential diagnosis of pulmonary adverse events emerging in the context of new realities in providing medical care to cancer patients.

Aim. To assess feasibility and safety of checkpoint inhibitor immunotherapy in relapsed/refractory cHL in the context of the COVID-19 pandemic.

Materials & Methods. This is a retrospective analysis of adverse events of therapy and COVID-19 mortality, and incidence in 50 cHL patients who received immunotherapy at the Pirogov Medical Center in the period of spring COVID-19 pandemic in 2020.

Results. During the reported period (from March 11, 2020, when the COVID-19 pandemic was declared, to May 25, 2020) the group of 50 cHL patients showed relatively low overall incidence rate of newly diagnosed immune-mediated adverse events (14 %; n = 7). Severe adverse events were identified in 2 (4 %) patients. Bacterial infection incidence was 6 % (n = 3). Clinical signs of corona virus confirmed by subsequent laboratory COVID-19 tests were observed in 2 (4 %) patients. One patient died due to the non-COVID-19-associated reason. The main issue the center’s staff was faced with was the need for differential diagnosis between drug-induced (as well as immune-mediated) pulmonitis and COVID-19-associated pneumonia.

Conclusion. The retrospective analysis reveals that PD-1-inhibitor immunotherapy in cHL patients during the COVID-19 pandemic is a feasible method of therapy, but it requires high awareness. Special focus should be given to clinical and radiological similarities of COVID-19-associated pneumonia and pulmonitis as a complication of immunotherapy.

Keywords: classical Hodgkin’s lymphoma, immunotherapy, PD-1-inhibitors, COVID-19 pandemic.

Received: May 29, 2020

Accepted: June 28, 2020

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Immune Checkpoint Inhibitors in the Treatment of Lymphomas

KV Lepik

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Kirill Viktorovich Lepik, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: lepikkv@gmail.com

For citation: Lepik KV. Immune Checkpoint Inhibitors in the Treatment of Lymphomas. Clinical oncohematology. 2018;11(4):303–12.

DOI: 10.21320/2500-2139-2018-11-4-303-312


ABSTRACT

Programmed death receptors and ligands (PD-1 and PD-L1) are the best studied immune checkpoints (ICP) and are considered to be key factors of immune response control. The ability of tumor cells to affect the ICP receptors is one of the principal mechanisms of suppressing antitumor immunity. The development of ICP inhibitors creates an opportunity to control and activate immune response and opens new perspectives for immunotherapy of cancers, including lymphomas. The paper reviews the biological background for the use of ICP inhibitors in the treatment of classical Hodgkin’s and non-Hodgkin’s lymphomas and summarizes the clinical experience of their use. The new approaches for the creation of combination regimens with ICP are also highlighted.

Keywords: immune checkpoints (ICP), PD-1, PD-L1, classical Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, ICP inhibitors.

Received: March 25, 2018

Accepted: July 23, 2018

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Outcome of Classical Hodgkin’s Lymphoma Treatment Based on High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation: The Experience in the NI Pirogov Russian National Medical Center of Surgery

NE Mochkin, VO Sarzhevskii, YuN Dubinina, EG Smirnova, DA Fedorenko, AE Bannikova, DS Kolesnikova, VS Bogatyrev, NM Faddeev, VYa Mel’nichenko

NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Nikita Evgen’evich Mochkin, MD, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: 8(495)603-72-17; e-mail: nickmed@yandex.ru

For citation: Mochkin NE, Sarzhevskii VO, Dubinina YuN, et. al. Outcome of Classical Hodgkin’s Lymphoma Treatment Based on High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation: The Experience in the NI Pirogov Russian National Medical Center of Surgery. Clinical oncohematology. 2018;11(3):234–40.

DOI: 10.21320/2500-2139-2018-11-3-234-240


ABSTRACT

Aim. To estimate the long-term outcome of the programmed treatment of classical Hodgkin’s lymphoma (cHL) including high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) as well as the effect of various factors on the achieved results in a single-center study.

Materials & Methods. In the A.A. Maksimov Clinical Center of Hematology and Cellular Therapy of the NI Pirogov Russian National Medical Center of Surgery 260 cHL patients received HDCT combined with auto-HSCT within the period from December 2006 to March 2017. The median age was 29 years (range 17–62). The study included 40 % men (n = 104), and 60 % women (n = 156). The median pretransplantation chemotherapy line was 3 (range 2–9). At this stage, prior to auto-HSCT, complete remission (CR) rate was 26.5 %, partial remission (PR) rate was 52.3 %, disease stabilisation rate was 13.5 %. HDCT with auto-HSCT was applied beyond progression as a salvage therapy in 7.7 % of patients. In 79.6 % of patients the standard BEAM and CBV conditioning regimens were used.

Results. After HDCT combined with auto-HSCT overall 5-year survival (OS) of 260 cHL patients was 74 %, and 5-year progression-free survival (PFS) was 48 %, which corresponds to the results of some international studies. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during the first CR or PR (85 %) vs the second and subsequent CR and PR (71 %). Neither gender (= 0.4) nor ECOG status (= 0.2) effects on OS and PFS were revealed. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during CR or PR (82 %) vs disease stabilisation and progression (54 %) as well as upon achieving CR (93 %) vs PR (77 %).

Conclusion. In cHL tumor sensitivity to chemotherapy is the essential indication for HDCT combined with auto-HSCT. The optimal time for HDCT and auto-HSCT in cHL is the first CR/PR, and the best treatment outcome is achieved in patients with complete response prior to HDCT and auto-HSCT.

Keywords: classical Hodgkin’s lymphoma, high-dose chemotherapy, autologous hematopoietic stem cell transplantation.

Received: February 9, 2018

Accepted: May 3, 2018

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Epstein-Barr Virus in Patients with Classical Hodgkin’s Lymphoma

VE Gurtsevitch, EA Demina, NB Senyuta, IV Botezatu, KV Smirnova, TE Dushen’kina, DM Maksimovich, UV Paramonova, IS Monin, AV Lichtenshtein

NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Prof. Vladimir Eduardovich Gurtsevitch, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: 8(499)324-25-64; e-mail: gurtsevitch-vlad-88@yandex.ru

For citation: Gurtsevitch VE, Demina EA, Senyuta NB, et al. Epstein-Barr Virus in Patients with Classical Hodgkin’s Lymphoma. Clinical oncohematology. 2018;11(2):160–6.

DOI: 10.21320/2500-2139-2018-11-2-160-166


ABSTRACT

Background. A close relationship between Epstein-Barr virus (EBV) and classical Hodgkin’s lymphoma (cHL) has been established in approximately 1/3 patients. EBV-positive lymphomas are characterized by increased level of EBV specific antibodies emerging long before tumor symptoms, аs well as a high plasma EBV DNA concentration. These viral markers normally correlate with clinical manifestations and the outcome of treatment performed. In patients with EBV-negative lymphomas, however, there has been no attempt to assess the clinical significance of either humoral response to EBV or EBV DNA concentration in plasma.

Aim. To evaluate diagnostic and prognostic significance of EBV markers in patients with EBV-negative lymphomas.

Methods. The clinical trial included 13 cHL-patients admitted at the Department of chemotherapy of hemoblastoses of NN Blokhin National Medical Cancer Research Center. The male to female ratio was 1:1.3, the median age was 26.4 years. Leukocyte and lymphocyte counts were evaluated in all the patients before, during, and after treatment as well as throughout the follow-up period. The same indicators were analysed in the control group which contained 40 healthy persons (with the median age of 41.1 years, male to female ratio 1.5:1). The study was based on serologic test for EBV antibodies and quantitative analysis of the viral DNA copy number in plasma.

Results. The obtained data show a low immunie response to EBV and its diminishment after several polychemotherapy treatment cycles, correlating with decreased leukocyte and lymphocyte levels. As opposed to levels of virus-specific antibodies which do not reflect the efficacy of anticancer therapy, plasma EBV DNA concentration in 2 patients decreased to 0 after remission had been achieved.

Conclusion. Although the number of observations is limited, one could suggest that viral load values in plasma of patients with EBV-negative lymphomas can prove to be a useful marker of anticancer therapeutic effect. Additional studies of these markers are required.

Keywords: Epstein-Barr virus (EBV), classical Hodgkin’s lymphoma, EBV DNA, EBV-negative classical Hodgkin’s lymphoma, level of virus-specific antibodies.

Received: November 13, 2017

Accepted: February 8, 2018

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