immunotherapy

Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas

AUTOIMMUNE THROMBOCYTOPENIA , , , ,

In memory of Academician A.I. Vorob’ev,
Russian Academy of Medical Sciences and Russian Academy of Sciences

KA Sychevskaya, SK Kravchenko, FE Babaeva, AE Misyurina, AM Kremenetskaya, AI Vorob’ev

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Kseniya Andreevna Sychevskaya, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(910)409-79-44; e-mail: sychevskaya-ka@yandex.ru

For citation: Sychevskaya KA, Kravchenko SK, Babaeva FE, et al. Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas. Clinical oncohematology. 2021;14(2):204–19. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-204-219

ABSTRACT

Background. Chronology of granulopoiesis based on periodic hematopoiesis model has been thoroughly studied. However, the pattern of influence of chemotherapy- and immunotherapy-induced cytotoxic stress on the development rhythm of a stem cell requires further investigation. The interaction of antitumor drugs with normal hematopoietic cells is relevant for assessing the intensity of chemotherapy adverse events. Besides, there is a demand for studying hematopoiesis under cytotoxic stress to predict immunological reactivity as a condition for efficacy of immunotherapeutic agents, the effect of which is based on cell immunity.

Aim. To study the chronological pattern of leukocyte count dynamics after R(G)-DHAP immunochemotherapy in non-Hodgkin’s lymphomas.

Materials & Methods. The dynamics of leukocyte count changes after R(G)-DHAP immunochemotherapy was analyzed using the data of 39 treatment courses in 19 non-Hodgkin’s lymphomas patients. After 18 out of 39 cycles of treatment granulocyte colony-stimulating factor (G-CSF) was administered to prevent granulocytopenia, in other cases the previously planned hematopoietic stem cell mobilization was performed according to the accepted protocol.

Results. Time to activation of spontaneous granulopoiesis depends neither on G-CSF stimulation, nor on the total dose of growth-stimulating factor and corresponds on average to Day 10 or Day 11 of the break from the last day of immunochemotherapy. The tendency of shorter agranulocytosis duration on prophylactic use of G-CSF is associated with transient hyperleukocytosis at an early stage after completing immunochemotherapy. Regimens with platinum-based drugs, like R(G)-DHAP, are suggested to be combined with immunochemotherapeutic agents in patients with the failure of first-line chemotherapy. The time interval preceding myelopoiesis activation within the first days of the break between the courses is likely to contribute to the initiation of treatment with immunotherapeutic drugs after second-line chemotherapy.

Conclusion. The determination of granulopoiesis dynamics under R(G)-DHAP immunochemotherapy-induced cytotoxic stress enables to plan the optimum G-CSF regimen and to predict the optimum timing of immune antitumor effect combined with chemotherapy.

Keywords: periodic hematopoiesis, mathematical hematopoiesis model, non-Hodgkin’s lymphomas, chemotherapy, immunotherapy, G-CSF, antitumor immunity, R(G)-DHAP.

Received: November 15, 2020

Accepted: February 25, 2021

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Nivolumab in a Primary Refractory Hodgkin’s Lymphoma Patient with Absolute Lymphopenia Prior to Chemotherapy: Literature Review and a Case Report

AUTOIMMUNE THROMBOCYTOPENIA ,

TI Bogatyreva, AO Afanasov, NA Falaleeva, LYu Grivtsova, AYu Terekhova

AF Tsyb Medical Radiological Research Centre, branch of the NMRC of Radiology, 4 Koroleva str., Obninsk, Kaluga Region, Russian Federation, 249036

For correspondence: Tatyana Ivanovna Bogatyreva, MD, PhD, 4 Koroleva str., Obninsk, Kaluga Region, Russian Federation, 249036; e-mail: bogatyreva@mrrc.obninsk.ru

For citation: Bogatyreva TI, Afanasov AO, Falaleeva NA, et al. Nivolumab in a Primary Refractory Hodgkin’s Lymphoma Patient with Absolute Lymphopenia Prior to Chemotherapy: Literature Review and a Case Report. Clinical oncohematology. 2021;14(2):179–87. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-179-187

ABSTRACT

The paper presents a case report of PET-adapted therapy of primary refractory classical Hodgkin’s lymphoma, stage IIАХ, in a female patient with absolute lymphopenia prior to chemotherapy. It also provides literature review on the choice of clinical management for similar categories of patients. Nivolumab was prescribed to the patient in February 2019 due to Hodgkin’s lymphoma progression after the failure of 4 chemotherapy lines including brentuximab vedotin. A bulk of mediastinal lymph nodes was exposed to radiation. Complete metabolic response was retained 18 months after nivolumab therapy start and 6 months after its discontinuation. The initial lymphopenia in this patient with primary refractory Hodgkin’s lymphoma did not interfere with the realization of full clinical effect of nivolumab.

Keywords: classical Hodgkin’s lymphoma, absolute lymphopenia, chemotherapy-refractory disease, immunotherapy, salvage therapy.

Received: September 9, 2020

Accepted: February 18, 2021

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    [Bogatyreva TI, Terekhova AYu, Shklyaev SS, et al. Treatment outcomes in patients with relapsed/refractory Hodgkin’s lymphoma: analysis of 142 successive cases. Evraziiskii onkologicheskii zhurnal. 2020;8(Suppl 2):229. (In Russ)]

Checkpoint Inhibitors and Classical Hodgkin’s Lymphoma: Efficacy and Safety of Pembrolizumab in Relapsed/Refractory Tumor (Experience at the NI Pirogov Russian National Medical Center of Surgery)

AUTOIMMUNE THROMBOCYTOPENIA ,

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

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

For correspondence: Prof. 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. Checkpoint Inhibitors and Classical Hodgkin’s Lymphoma: Efficacy and Safety of Pembrolizumab in Relapsed/Refractory Tumor (Experience at the NI Pirogov Russian National Medical Center of Surgery). Clinical oncohematology. 2021;14(1):53–62. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-53-62

ABSTRACT

Background. Checkpoint inhibitors contribute to improving the treatment outcomes in patients with relapsed/refractory classical Hodgkin’s lymphoma (cHL). The paper describes the first generalized experience with pembrolizumab-inducing cHL immunotherapy in Russia. The hallmark of the study is a long follow-up period.

Aim. To retrospectively assess efficacy and safety of pembrolizumab-inducing immunotherapy of relapsed/refractory cHL.

Materials & Methods. The study enrolled 14 cHL patients: 3 men and 11 women aged 24–57 years (median 33 years). Pembrolizumab 200 mg or 2 mg/kg was intravenously administered every 3 weeks. Median pembrolizumab administration number was 27 (max. 52 administrations), median follow-up after immunotherapy onset was 31 months.

Results. Complete response (as best response) was achieved in 8 (57 %) patients, 3 (21 %) patients showed partial response (as best response). Overall objective response was 78 %. Median number of pembrolizumab administrations resulting in better responses to immunotherapy was 4, which corresponded to 3 months of treatment. Maximum number of pembrolizumab administrations before achieving best response was 32. Best response duration (the period from achieving it to disease progression/relapse or to the end-point of data collection in case of sustained response) varied from 3 to 56 months (median 15 months). Most common severe adverse events of grade 3–4 were pulmonary complications. Overall survival for 12, 24, and 36 months was 92.9 %, 85.7 %, and 85.7 %, respectively, and progression-free survival was 76.9 %, 59.3 %, and 37.1 %, respectively; median time before progression was 27.7 months.

Conclusion. The experience with pembrolizumab-inducing immunotherapy of relapsed/refractory cHL in Russia proves the efficacy and relative safety of this treatment approach. Due to long follow-up period a series of crucial practical immunotherapy-related issues were raised, which will need to be dealt with in future studies.

Keywords: сheckpoint inhibitors, immunotherapy, classical Hodgkin’s lymphoma, pembrolizumab.

Received: September 7, 2020

Accepted: December 2, 2020

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Статистика Plumx английский

REFERENCES

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  13. Manson G, Brice P, Herbaux C, et al. Efficacy of anti-PD1 Re-Treatment in Patients With Hodgkin Lymphoma Who Relapsed After anti-PD1 Discontinuation. Haematologica. 2020;105. [Epub ahead of print] doi: 10.3324/haematol.2019.242529.
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The Use of Checkpoint Inhibitors in Classical Hodgkin’s Lymphoma during the COVID-19 Pandemic (Pirogov Medical Center’s Experience)

AUTOIMMUNE THROMBOCYTOPENIA ,

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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  11. 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.

  12. Chen R, Zinzani P, Fanale M, 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.

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  14. Rochefoucauld J, Noel N, Lambotte O. Management of Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Cancer Patients: A Patient-Centred Approach. Intern Emerg Med. 2020. doi: 10.1007/s11739-020-02295-2.

  15. Diamantopoulos P, Gaggadi M, Kassi E, et al. Late-onset Nivolumab-Mediated Pneumonitis in a Patient With Melanoma and Multiple Immune-Related Adverse Events. Melanoma Res. 2017;27(4):391–5. doi: 10.1097/CMR.0000000000000355.

Theory and Practice of Immunotherapy Directed against the PRAME Antigen

REVIEWS , , , , ,

VA Misyurin

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

For correspondence: Vsevolod Andreevich Misyurin, PhD in Biology, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(985)4363019; e-mail: vsevolod.misyurin@gmail.com

For citation: Misyurin VA. Theory and Practice of Immunotherapy Directed against the PRAME Antigen. Clinical oncohematology. 2018;11(2):138–49.

DOI: 10.21320/2500-2139-2018-11-2-138-149

ABSTRACT

The preferentially expressed antigen of melanoma (PRAME) is a significant target for monoclonal antibodies and an oncospecific marker known for its activity on all the tumor cell differentiation stages and its eliciting of a spontaneous T-cell response. Since PRAME protein is active in approximately every second patient with solid tumors and oncohematological diseases, anti-PRAME immunotherapy is very promising. In current review the mechanism of spontaneous immune response against PRAME is discussed as well as the role of this antigen in immunosurveillance. The review deals with the PRAME-specific T-cell genesis and risk assessment of immunotherapy directed against PRAME-positive cells. The risks and benefits of various immunotherapy approaches including the use of dendritic cell vaccines, PRAME vaccination, development of specific T-cells, and development of specific monoclonal antibodies were analysed. Possible causes of treatment failure are analysed, and methods of overcoming them are suggested. The literature search in the Pubmed, Scopus, and eLibrary databases, with the use of “PRAME” as a keyword was performed. Only publications related to various aspects of immunotherapy and anti-PRAME-specific agents were included in the review.

Keywords: PRAME, immunotherapy, dendritic cell vaccines, peptide vaccines, T-cell vaccines, therapeutic antibodies.

Received: December 19, 2017

Accepted: February 5, 2018

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