classical Hodgkin’s lymphoma

Prognostic Value of the Degree of Tumor Tissue Infiltration by CD15-Positive Granulocytes in Nodular Sclerosis Classical Hodgkin’s Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA

EA Perfilova, DA D’yakonov, MS Minaev

Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027

For correspondence: Elena Aleksandrovna Perfilova, PhD in Veterinary Medicine, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(996)896-08-67; e-mail: lperf78@gmail.com

For citation: Perfilova EA, D’yakonov DA, Minaev MS. Prognostic Value of the Degree of Tumor Tissue Infiltration by CD15-Positive Granulocytes in Nodular Sclerosis Classical Hodgkin’s Lymphoma. Clinical oncohematology. 2022;15(3):253–8. (In Russ).

DOI: 10.21320/2500-2139-2022-15-3-253-258

ABSTRACT

Classical Hodgkin’s lymphoma (cHL) nodular sclerosis type is one of the most common malignant lymphoproliferative diseases among younger people. The tumor is considered to be potentially curable. However, despite successful application of standard treatment methods, primary resistance and relapses occur. At present, many researchers focus on studying the value of tumor microenvironment in the prognosis of the course and progression of cHL, aiming at identifying new therapeutic targets. The present paper shows that the relative count of CD15-positive granulocytes in patients with favorable course of the disease is significantly lower than in therapy-refractory patients. The cut-off of tumor microenvironment cells expressing CD15 was 8 %. The data obtained provide the basis for determining prognostic value of CD15-positive granulocytes in nodular sclerosis cHL and presenting this cell pool as a potential therapeutic target.

Keywords: classical Hodgkin’s lymphoma, nodular sclerosis, CD15 granulocytes, tumor microenvironment.

Received: April 8, 2022

Accepted: June 17, 2022

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Статистика Plumx английский

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The Efficacy of Brentuximab Vedotin in Relapsed/Refractory Classical Hodgkin’s Lymphoma and Quality of Life: Results of a Multi-Center Observational Prospective Study in the Context of Real Clinical Practice

AUTOIMMUNE THROMBOCYTOPENIA , ,

TI Ionova1,2, AA Amdiev3, MI Andrievskikh4, EA Baryakh5, EV Vasilev6, MV Volkov7, EM Volodicheva8, VV Ivanov9, OV Kaverina10, KD Kaplanov11, TYu Klitochenko12, VI Kurakin13, DG Lazareva10, OG Larionova7, KV Lepik14, IB Lysenko15, VYa Melnichenko16, RI Minullina17, OV Mironov18, EN Misyurina5, NB Mikhailova14, NE Mochkin16, TP Nikitina1,2, TS Petrova17, NM Porfireva1, OA Rukavitsyn19, AA Samoilova16, RN Safin17, PI Simashova19, EG Smirnova16, NA Trenina13, NV Fadeeva4, GN Khusainova17, VL Chang18, TV Shelekhova20, DG Sherstnev20

1 Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., Saint Petersburg, Russian Federation, 191014

2 NI Pirogov Clinic for High Medical Technology, Saint Petersburg State University, 154 Fontanki emb., Saint Petersburg, Russian Federation, 198103

3 VM Efetov Crimea Republican Clinical Oncology Dispensary, 49A Bespalova str., Simferopol, Russian Federation, 295007

4 Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine, 42 Blyukhera str., Chelyabinsk, Russian Federation, 454087

5 Municipal Clinical Hospital No. 52, 5 Marshala Katukova str., Moscow, Russian Federation, 123181

6 Krasnoyarsk Krai Clinical Hospital, 3A Partizana Zheleznyaka str., Krasnoyarsk, Russian Federation, 660022

7 Primorsky Krai Oncology Dispensary, 59 Russkaya str., Vladivistok, Russian Federation, 690105

8 Tula Regional Clinical Hospital, 1A bld. 1 Yablochkova str., Tula, Russian Federation, 300053

9 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

10 Altai Krai Oncology Dispensary, 110 Zmeinogorskii passage, Barnaul, Russian Federation, 656045

11 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

12 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

13 Clinical Oncology Dispensary, 9 bld. 1 Zavertyaeva str., Omsk, Russian Federation, 644013

14 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

15 National Medical Cancer Research Center, 63 bld. 8 14th line str., Rostov-on-Don, Russian Federation, 344037

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

17 Tatarstan Republican Clinical Oncology Dispensary, 29 bld. A Sibirskii passage, Kazan, Russian Federation, 420029

18 Tambov Regional Clinical Oncology Dispensary, 29B Moskovskaya str., Tambov, Russian Federation, 392000

19 NN Burdenko Central Military Clinical Hospital, 3 Gospital’naya sq., Moscow, Russian Federation, 105229

20 VI Razumovskii Saratov State Medical University, 6/9 53rd Strelkovoi Divizii str., Saratov, Russian Federation, 410028

For correspondence: Tatyana Pavlovna Nikitina, MD, PhD, 1 Artilleriiskaya str., Saint Petersburg, Russian Federation, 191014; e-mail: qolife@mail.ru

For citation: Ionova TI, Amdiev AA, Andrievskikh MI, et al. The Efficacy of Brentuximab Vedotin in Relapsed/Refractory Classical Hodgkin’s Lymphoma and Quality of Life: Results of a Multi-Center Observational Prospective Study in the Context of Real Clinical Practice. Clinical oncohematology. 2022;15(1):42–53. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-42-53

ABSTRACT

Aim. To study the quality of life and symptoms, to assess the clinical effect and treatment safety in relapsed/refractory classical Hodgkin’s lymphoma (r/r cHL) patients treated with brentuximab vedotin (BV) as ≥ 3rd-line therapy in the context of real clinical practice.

Materials & Methods. The study enrolled 62 r/r cHL patients after the second- and subsequent-line chemotherapies, who are either ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) at the time of their enrollment into the study or after the failure of high-dose chemotherapy (HDCT) with auto-HSCT. The median age was 31 years; 46.8 % of patients were women. The patients received BV 1.8 mg/kg intravenously every 3 weeks. Clinical parameters, quality of life, and symptoms were assessed prior to BV therapy and in 3, 6, 9, 12, and 15 months after therapy onset. The RAND SF-36 form was used to assess the quality of life, and the ESAS-R tool was applied to report on symptoms.

Results. Objective response was observed in 68.3 % of patients, 40 % out of them showed complete response. The median progression-free survival was 10.6 months (95% confidence interval 7.4–12.9 months). Safety profile corresponded to the published data. Adverse events of grade 3/4 were identified in 1.6 % of patients. In the period of 15 months after therapy onset, quality of life improvement or stabilization was reported based on all the scales of RAND SF-36 (GEE, p < 0.001), and symptom abatement was proved based on ESAS-R total score (GEE, p < 0.001).

Conclusion. In the context of real clinical practice, BV appeared to be effective in r/r cHL patients either after the second- or subsequent-line chemotherapies or after the failure of HDCT with auto-HSCT. The study demonstrated that BV was well tolerated by the patients. BV therapy contributes to the improvement of r/r cHL patients’ quality of life. Positive changes in quality of life and symptoms on BV therapy testify to its patient-assessed efficacy.

Keywords: classical Hodgkin’s lymphoma, relapsed/refractory form, brentuximab vedotin, quality of life, real clinical practice.

Received: June 29, 2021

Accepted: November 19, 2021

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Статистика Plumx английский

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Results of the Russian Multi-Center Cooperative Prospective-Retrospective Observational Program for Hodgkin’s Lymphoma Treatment RNWOHG-HD1

AUTOIMMUNE THROMBOCYTOPENIA ,

IS Moiseev1, SM Alekseev2,24, NB Mikhailova1, KD Kaplanov3,21, MV Demchenkova4, LV Anchukova5, VV Baikov1, AM Belyaev2, YuA Vasil’eva6, NP Volkov1, YuN Vinogradova7, AYu Zaritskey8, AE Zdorov9, NV Il’in7, LO Kashintseva10, EV Kondakova1, PV Kotselyabina1, VA Lapin11, KV Lepik1, IV Lesechko12, VM Moiseenko13, GM Manikhas14, NV Medvedeva15, YuA Oleinik2, ES Pavlyuchenko16, KS Parfenova17, EV Patrakova18, AV Proidakov19, DV Saidullaeva20, EV Tarasova21, AL Shipaeva22, TV Shneider23, BV Afanasyev1

1 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

2 NN Petrov National Medical Cancer Research Center, 68 Leningradskaya str., Pesochnyi settlement, Saint Petersburg, Russian Federation, 197758

3 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

4 Regional Oncology Dispensary, 32 Frunze str., Irkutsk, Russian Federation, 664035

5 Vologda Regional Clinical Hospital, 17 Lechebnaya str., Vologda, Russian Federation, 160002

6 Pskov Oncology Dispensary, 15a Vokzalnaya str., Pskov, Russian Federation, 180004

7 AM Granov Russian Research Centre for Radiology and Surgical Technologies, 70 Leningradskaya str., Pesochnyi settlement, Saint Petersburg, Russian Federation, 197758

8 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

9 VA Baranov Republican Hospital, 3 Pirogova str. (Perevalka district), Petrozavodsk, Republic of Karelia, Russian Federation, 185002

10 Tula Regional Clinical Hospital, 1a Yablochkova str., Tula, Russian Federation, 300053

11 Yaroslavl Regional Clinical Hospital, 7 Yakovlevskaya str., Yaroslavl, Russian Federation, 150062

12 Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya str., Stavropol, Russian Federation, 355047

13 Saint Petersburg Clinical Applied Research Center for Specialized Types of Medical Care (Oncology), 68A Leningradskaya str., Pesochnyi settlement, Saint Petersburg, Russian Federation, 197758

14 Municipal Clinical Oncology Dispensary, 3/5 2-ya Berezovaya alley, Saint Petersburg, Russian Federation, 197022

15 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

16 EE Eikhvald Clinic, II Mechnikov North-Western State Medical University, 41 bld. 7 Kirochnaya str., Saint Petersburg, Russian Federation, 191123

17 Samara Regional Clinical Oncology Dispensary, 11 Solnechnaya str., Syzran, Russian Federation, 446020

18 Vologda Regional Clinical Hospital No. 2, 15 Danilova str., Cherepovets, Vologda Region, Russian Federation, 162602

19 Komi Republican Oncology Dispensary, 46 Nyuvchimskoe sh., Krasnozatonskii town settlement, Syktyvkar, Republic of Komi, Russian Federation, 167904

20 Tver Regional Oncology Dispensary, 57/37 15 let Oktyabrya str., Tver, Russian Federation, 170008

21 First Republican Clinical Hospital, 57 Votkinskoe sh., Izhevsk, Russian Federation, 426039

22 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

23 Leningrad Regional Clinical Hospital, 45 bld. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

24 LD Roman Leningrad Regional Clinical Oncology Dispensary, 2 Zaozernaya str., Kuzmolovskii settlement, Vsevolozhskii district, Leningrad Region, Russian Federation, 188663

For correspondence: Ivan Sergeevich Moiseev, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: 8(812)338-62-65; e-mail: moisiv@mail.ru

For citation: Moiseev IS, Alekseev SM, Mikhailova NB, et al. Results of the Russian Multi-Center Cooperative Prospective-Retrospective Observational Program for Hodgkin’s Lymphoma Treatment RNWOHG-HD1. Clinical oncohematology. 2021;14(4):455–65. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-455-465

ABSTRACT

Aim. The observational program was aimed at obtaining data on classical Hodgkin’s lymphoma (cHL) incidence in the Russian Federation, therapy options, and clinical outcomes of treatment. The aim of the prospective part of the program was to standardize the approaches to therapy and to compare its outcomes with off-protocol treatment.

Materials & Methods. The prospective-retrospective observational program for Hodgkin’s lymphoma treatment engaged 32 regional and federal centers. It included 218 patients, 21 out of them were included into the prospective part of the RNWOHG-HD1 (Russian North-West Oncology and Hematology Group — Hodgkin Disease Study 1) program. The median age was 36 years (range 22–87 years). cHL stages I/II were identified in 48 % of patients, III/IV stages were reported in 52 % of patients. The prospective part of the program used escalating protocol in patients with stages I/IIA and without risk factors and de-escalating protocol in patients with advanced stages. Overall (OS) and progression-free (PFS) survivals were analyzed in 160 and 152 patients, respectively. PET-CT was used to assess the response in 33 % of patients.

Results. The study used the following first-line chemotherapy regimens: ABVD in 42 %, BEACOPPst in 11 %, BEACOPP-14 in 17 %, BEACOPPesc in 25 %, and EACOPP in 1 % of cases. After the completion of first-line therapy objective response rate was 91 % including 61 % of complete responses. Response structure did not significantly differ in the groups of non-intensive therapy (ABVD and BEACOPPst), intensified regimens (BEACOPP-14, BEACOPPesc, and EACOPP), and treatment according to the RNWOHG-HD1 protocol (91 %, 92 %, and 96 %, respectively; p = 0.7226). In the total cohort the 3-year OS was 97 % (95% confidence interval [95% CI] 94–99 %), PFS was 87 % (95% CI 80–92 %). The 3-year PFS did not differ in ABVD, BEACOPPst, BEACOPP-14, BEACOPPesc, and RNWOHG-HD1 recipients (p = 0.37). International Prognostic Score (IPS) yielded significant results in PFS prediction for patients with IPS score of 5–6, but not for those with IPS score of 1–4 (p = 0.0028).

Conclusion. The observational program showed that the majority of participating centers use the risk-adapted ABVD/BEACOPPesc approach which explains no difference in PFS being found with the use of these chemotherapy options. The study demonstrated the need for PET-CT to assess the response since the CT alone cannot distinguish between complete and partial responses in a considerable number of patients. The prospective unified program for cHL treatment may well be implemented in the Russian Federation.

Keywords: classical Hodgkin’s lymphoma, multi-center study, ABVD, BEACOPP, positron emission tomography, risk-adapted therapy.

Received: May 25, 2021

Accepted: August 30, 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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    [Demina EA, Leont’eva AA, Tumyan GS, et al. First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data). Clinical oncohematology. 2017;10(4):443–52. doi: 10.21320/2500-2139-2017-10-4-443-452. (In Russ)]
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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

  1. Ansell S, Lesokhin A, 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.
  2. 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.
  3. Armand P, Shipp MA, Ribrag V, et al. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016;34(31):3733–9. doi: 10.1200/JCO.2016.67.3467.
  4. 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.
  5. Zinzani P, Lee H, Armand P, et al. Three-Year Follow-up of Keynote-087: Pembrolizumab Monotherapy in Relapsed/Refractory Classic Hodgkin Lymphoma. 2019;134(Suppl_1):240. doi: 10.1182/blood-2019-127280.
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    [Lepik KV. Effektivnost i bezopasnost PD-1 ingibitora (nivolumaba) v lechenii rezistentnoi i retsidiviruyushchei limfomy Khodzhkina. (Efficacy and safety of PD-1 inhibitor (nivolumab) in the treatment of relapsed/refractory Hodgkin’s lymphoma.) [dissertation] Saint Petersburg; 2019. (In Russ)]
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  11. Ansell S, Armand Р, Timmerman J, et al. Nivolumab re-treatment in patients with relapsed/refractory Hodgkin lymphoma: safety and efficacy outcomes from a phase 1 clinical trial. Poster presentation at the 10th International Symposium on Hodgkin Lymphoma (ISHL); October 22–25, 2016; Cologne, Germany. Abstract 583/P090.
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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.
  14. Armand P, Kuruvilla J, Michot J-M, et al. KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure. Blood Adv. 2020;4(12):2617–22. doi: 10.1182/bloodadvances.2019001367.
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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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  10. Ansell S, Lesokhin A, 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.

  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.

Immune Checkpoint Inhibitors in the Treatment of Lymphomas

REVIEWS , , ,

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

BONE MARROW TRANSPLANTATION , ,

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 (p = 0.4) nor ECOG status (p = 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

LYMPHOID TUMORS , , , ,

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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