Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice

KV Lepik1, NP Volkov1, NB Mikhailova1, EV Kondakova1, LA Tsvetkova1, YuR Zalyalov1, EE Lepik1, LV Fedorova1, AV Beinarovich1, MV Demchenkova2, OG Smykova1, PV Kotselyabina1, IS Moiseev1, VV Baikov1, 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 Regional Oncologic Dispensary, 32 Frunze str., Irkutsk, Russian Federation, 664035

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

For citation: Lepik KV, Volkov NP, Mikhailova NB, et al. Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice. Clinical oncohematology. 2020;13(3):280–8 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-280-288


ABSTRACT

Aim. To assess prognostic factors and to analyze the outcomes of nivolumab therapy in patients with relapsed/refractory classic Hodgkin’s lymphoma (cHL) after autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The retrospective analysis included 42 patients treated with nivolumab 3 mg/kg after auto-HSCT in the period from 2016 to 2020. The response to nivolumab therapy was assessed every three months by whole-body PET/CT based on LYRIC criteria. Toxicity profile was assessed by establishing adverse events (AE) based on NCI CTCAE 4.03 criteria.

Results. The study included 42 patients with relapsed/refractory cHL: 21 (50 %) men and 21 (50 %) women. The median age was 32.5 years (range 22–43 years). At diagnosis the following cHL stages were identified: stage II in 14 pts (33.3 %), stage III in 12 pts (28.6 %), and stage IV in 16 pts (38.1 %). Primary chemoresistance after the first-line therapy was observed in 26 pts (61.9 %) and early relapse in 4 pts (9.52 %). The median follow-up was 38 months, 3-year overall survival was 97 % (95% confidence interval, 95% CI, 83.2–99.6 %), 3-year progression-free survival (PFS) was 34.8 % (95% CI 20.3–49.9 %; median 12.9 months). Objective response was reported in 69 % of patients, complete response (CR) in 33.3 %, partial response in 35.7 %, stable disease in 7.1 %, indeterminate response in 14.3 %, and progression in 9.5 % of patients. The analysis of factors affecting PFS revealed significant differences in patients who reached CR after 6 nivolumab cycles: 3-year PFS 56.2 % (95% CI 24.4–79.1 %) vs. 25.2 % (95% CI 10.46–43.1 %) in patients who did not reach CR (= 0.054). If extranodal lesions were identified at nivolumab therapy onset, PFS was 29 % (95% CI 7.8–37.5 %) vs. 68 % (95% CI 35.9–86.8 %) in their absence (= 0.0079). The overall rate of AEs on nivolumab therapy was 92.9 %, severe AEs of grade 3–4 were observed in 19.1 % of patients.

Conclusion. Nivolumab shows high efficacy in the treatment of patients with relapsed/refractory cHL after the failure of auto-HSCT and considerably improves prognosis compared with historical control. The efficacy of nivolumab is independent of brentuximab vedotin use and duration of prior therapy. Throughout the follow-up period the toxicity level of nivolumab was acceptable and controlled. Clinical factors that affect prognosis for patients on immunotherapy were identified.

Keywords: Hodgkin’s lymphoma, nivolumab, brentuximab vedotin, auto-HSCT, immunotherapy.

Received: March 24, 2020

Accepted: June 15, 2020

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Bendamustine in the Treatment of Relapsed/Refractory Hodgkin’s Lymphoma: Literature Review and Clinical Experience

SS Shklyaev, NA Falaleeva, TI Bogatyreva, AYu Terekhova, MA Danilova

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

For correspondence: Stanislav Sergeevich Shklyaev, MD, PhD, 4 Koroleva str., Kaluga Region, Obninsk, Russian Federation, 249036; Tel.: +7(484)399-30-31; e-mail: staniss1@yahoo.com

For citation: Shklyaev SS, Falaleeva NA, Bogatyreva TI, et al. Bendamustine in the Treatment of Relapsed/Refractory Hodgkin’s Lymphoma: Literature Review and Clinical Experience. Clinical oncohematology. 2020;13(2):136–49 (In Russ).

DOI: 10.21320/2500-2139-2020-13-2-136-149


ABSTRACT

Aim. To assess the efficacy of bendamustine combined with dexamethasone in the treatment of relapsed/refractory Hodgkin’s lymphoma (HL).

Materials & Methods. The article provides an updated review of literature as well as the data of prospective observational clinical trial in 47 HL patients (17 men and 30 women aged 20–65 years, median age 36 years) with relapses after standard and high-dose chemotherapy with autologous hematopoietic stem cell transplantation. The therapy regimen included 120 mg/m2 of bendamustine IV on Days 1 and 2 and 20 mg of oral dexamethasone from Day 1 to Day 4. Retreatment was administered 21 days after the start of the previous one. Radiotherapy was applied only to the regions of massive relapsed lesions and bone destructions with pain syndrome.

Results. From April 2011 to September 2017 all 47 patients received 149 bendamustine + dexamethasone therapy regimens with the overall response of 57 % (complete response 27 %, partial response 30 %). Disease progression on therapy was reported in 20 (43 %) patients, its incidence was the highest after the first (n = 8) or the second cycle (n = 4). In the group of 27 patients with overall response 19 (70 %) patients showed new relapses. In these cases the treatment-free period was from 8 to 31 months (median 11 months). The repeated administration of 57 bendamustine + dexamethasone therapy regimens in 12 out of 47 patients achieved clinical effect for 4–36 months (median 6 months). After the first failure of bendamustine-based therapy 13 patients were treated with brentuximab vedotin and nivolumab, the new salvage therapy drugs. With median follow-up of 22 months (range 1–69 months) median overall survival (OS) and time to the next progression were 35 and 10 months, respectively, in all patients. Multivariate analysis showed that OS was unfavorably affected only by B-symptoms on bendamustine + dexamethasone administration (= 0.046), and the time to the next progression was shorter in the presence of B-symptoms (= 0.017) and in histological variant “nodular sclerosis type II” (= 0.006).

Conclusion. Bendamustine + dexamethasone therapy is a relatively low-toxic and effective method of life prolongation in HL patients with chemotherapy-refractory tumors and recurrent relapses, provided no B-symptoms occur by the start of antitumor therapy.

Keywords: Hodgkin’s lymphoma, bendamustine, chemotherapy-refractory disease, relapses.

Received: December 15, 2019

Accepted: March 20, 2020

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Hodgkin’s Lymphoma: Analysis Results of Volgograd Regional Registry

KD Kaplanov1,2, NP Volkov1, TYu Klitochenko1, IV Matveeva1, AL Shipaeva1, MN Shirokova1, NV Davydova3, EG Gemdzhian4

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

2 Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081

3 Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081

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

For correspondence: Kamil Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Hodgkin’s Lymphoma: Analysis Results of Volgograd Regional Registry. Clinical oncohematology. 2019;12(4):363–76 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-363-376


ABSTRACT

Background. The present paper discusses feasibility of first- and second-line therapies as well as the significance of different risk factors in the population of all patients with newly diagnosed Hodgkin’s lymphomas (HL) in a 14-year period based on the data of Volgograd regional registry.

Materials & Methods. During the period 2003 to 2017 the population registry of Department of Hematology of Volgograd Regional Clinical Oncology Dispensary included the data of all the patients with newly diagnosed HL (n = 622): 272 (44 %) men and 350 (56 %) women aged 18 to 84 years (mean age 38 years, median age 33 years). There were 97 (16 %) patients with early stages and without risk factors, 165 (27 %) patients with early stages and risk factors, 360 (59 %) patients with advanced stages, 308 (50 %) patients with toxic symptoms (stage B), and 179 (29 %) patients with bulky tumor lesions (≥ 10 cm). ABVD treatment regimen was administered in 190 (30.5 %) patients, increased-dose BEACO(D)PP in 39 (6 %) patients, BEACO(D)PP-14 in 159 (26 %) patients, standard BEACO(D)PP in 200 (32 %) patients, IVDG in 25 (4 %) patients, and other regimens in 9 (1.5 %) patients. The second-line treatment was administered in 120 (19 %) out of 622 patients. By the end of August 2018, the number of followed-up patients was 514 (83 %), 108 (17 %) patients had died. The prognostic value of the International Prognostic Score (IPS), PET, and other factors was assessed by means of Cox’s multivariate regression analysis. Pharmacoeconomic analysis of differences between options of first-line therapy was based on Markov model.

Results. In the group of patients with advanced HL stages treated with escalated BEACO(D)PP (the increased-dose regimen and BEACO(D)PP-14) 5- and 10-year overall survival (OS) was 83 % and 74 %, respectively, OS median was not reached. On standard BEACO(D)PP patients with advanced HL stages had OS median of 139 months (11.6 years) and 5- and 10-year OS of 68 % and 54 %, respectively (= 0,012). In the group of patients with early stages and poor prognosis treated with escalated regimens BEACO(D)PP 5- and 10- year OS was 100 % and 90 %, respectively, in the combined group treated with ABVD and standard BEACO(D)PP it was 83 % and 75 % (= 0.035). Replacement of procarbazine with dacarbazine in the standard and increased-dose BEACOPP regimens did not affect treatment efficacy. Markov analysis demonstrated the advantages of the escalated regimens for treatment of early stages with poor prognosis and advanced stages in terms of life years gained. Out of 7 IPS factors male sex, age ≥ 45 years, hemoglobin < 105 g/L, and albumin < 40 mg/L significantly impacted OS. Based on these data an adjusted prognostic index was suggested.

Conclusion. The advantage of the escalated strategy of first-line therapy in HL is reflected in survival parameters and is based on pharmacoeconomic evidence. The significance of some laboratory IPS risk factors can be reviewed; most obvious is increasing importance of PET for predicting the need for salvage therapy.

Keywords: Hodgkin’s lymphoma, BEACO(D)PP, ABVD, International Prognostic Score, survival analysis, pharmacoeconomics, Markov model, life years gained (LYG), incremental cost-effectiveness ratio (ICER).

Received: February 21, 2019

Accepted: September 17, 2019

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PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma

EA Demina

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

For correspondence: Prof. Elena Andreevna Demina, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: drdemina@yandex.ru

For citation: Demina EA. PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma. Clinical oncohematology. 2018;11(3):213–19.

DOI: 10.21320/2500-2139-2018-11-3-213-219


ABSTRACT

During the last two decades individualization of programmed treatment combined with intensified chemotherapy has proven to be effective treatment for the majority of classical Hodgkin’s lymphoma (cHL) patients. However, in 10–30 % of cases relapses and resistance to therapy still occur. Further intensification of therapy induces toxicity that leads to decrease in overall survival and quality of life. The standard second-line treatment with high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) allows for the achievement of long-term 5-year progression-free survival only in 50–60 % of patients with relapsed disease and not more than 40–45 % of patients with refractory disease. Approximately 50 % of patients relapse after HDCT and auto-HSCT. The median overall survival of relapsed patients does not exceed 2 years. Allogeneic HSCT improves treatment results to some extent, but is not an optimal strategy in all patients. A search for new treatment options has been made to improve effectiveness of relapsed and refractory cHL treatment and to reduce toxicity of highly effective programs. А new CD30-targeted conjugate brentuximab vedotin was developed to use anti-CD30 monoclonal antibodies against a specific marker of tumor Reed-Sternberg cells allowing for the transfer of the highly effective antitumor compound of monomethyl auristatin E directly to tumor cells. This drug showed high effectiveness, although failed to provide a complete solution to the problem. The development of anti-PD1 antibody nivolumab opened up new opportunities for cHL treatment. This paper reviews literature information on pharmacological data and antitumor mechanisms of the drug as well as the results of significant international randomised studies.

Keywords: nivolumab, Hodgkin’s lymphoma, relapse, resistance, treatment.

Received: February 5, 2018

Accepted: April 30, 2018

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Polymerase Chain Reaction for Prognosis Assessment and Monitoring of the Epstein-Barr Virus-Associated Hodgkin’s Lymphoma

MA Katin1, IV Zhil’tsov1, VM Semenov1, DK Novik2

1 Vitebsk State Medical University, 27 Frunze pr-t, Vitebsk, Republic of Belarus, 210023

2 Republican Applied Research Center for Radiation Medicine and Human Ecology, 290 Il’icha str., Gomel, Republic of Belarus, 246040

For correspondence: Prof. Ivan Viktorovich Zhil’tsov, MD, PhD, 27 Frunze pr-t, Vitebsk, Republic of Belarus, 210023; Tel.: +375(29)7104368-93-29; e-mail: zhyltsou@tut.by

For citation: Katin NA, Zhil’tsov IV, Semenov VM, Novik DK. Polymerase Chain Reaction for Prognosis Assessment and Monitoring of the Epstein-Barr Virus-Associated Hodgkin’s Lymphoma. Clinical oncohematology. 2018;11(2):182–6.

DOI: 10.21320/2500-2139-2018-11-2-182-186


ABSTRACT

The review provides the analysis of 34 papers on polymerase chain reaction (PCR) as a method of the Epstein-Barr virus (EBV) DNA detection in biological material of patients with EBV-associated cancer diseases including Hodgkin’s lymphoma (HL). A comparative analysis of different methods of EBV DNA detection in biological material is presented. EBV is associated with HL in 20 to 100 % of cases depending on a geographic region and HIV status. EBV-associated HLs are characterized by latency type II. EBV is found in all the atypical cells and can be detected in blood of EBV-associated HL patients by means of the PCR method. The review includes the results of studies on EBV detection using the PCR method compared to in situ methods of hybridization and immunohistochemistry in various EBV-associated cancer diseases including HL. The obtained data indicate that PCR can be used for quantitative determination of EBV DNA in blood plasma of HL patients for therapeutic efficacy monitoring and prognosis assessment of disease and relapses. Quantitative determination of EBV DNA in blood plasma of HL patients using the real time PCR method is a promising technique. Its further practical application requires standardization of the method, larger trials, and comparison to positron emission tomography.

Keywords: Epstein-Barr virus, Hodgkin’s lymphoma, polymerase chain reaction.

Received: December 20, 2017

Accepted: February 28, 2018

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Conventional and Conformal Radiotherapy with and without Beam Intensity Modulation in Patients with Stage II Hodgkin’s Lymphoma with Supradiaphragmal Lesions

YuN Vinogradova1, EI Ivanova1, AI Chumachenko1, EV Smirnova2, GI Andreev2, AM Kalesnik2, NA Vorob’ev2, NV Il’in1

1 AM Granov Russian Research Centre of Radiology and Surgery Technologies, 70 Leningradskaya str., Pesochnyi, Saint Petersburg, Russian Federation, 197758

2 Nuclear Medicine Centre of SM Berezin International Institute of Biological Systems, 43 Karl Marx str., Pesochnyi, Saint Petersburg, Russian Federation, 197758

For correspondence: Nikolai Vasil’evich Il’in, PhD, Professor, 70 Leningradskaya str., Pesochnyi, Saint Petersburg, Russian Federation, 197758; Tel.: +7(812)596-90-35; e-mail: ilyin_prof@mail.ru.

For citation: Vinogradova YuN, Ivanova EI, Chumachenko AI, et al. Conventional and Conformal Radiotherapy with and without Beam Intensity Modulation in Patients with Stage II Hodgkin’s Lymphoma with Supradiaphragmal Lesions. Clinical oncohematology. 2018;11(1):70-7.

DOI: 10.21320/2500-2139-2018-11-1-70-77


ABSTRACT

Aim. To increase the efficacy of chemo-radiotherapy in patients with stage II Hodgkin’s lymphoma (HL) with supradiaphragmal lesions by different fractionation (conventional fractionation [CF] and multi-fractionation [MF]) and various radiation volume (mantle radiotherapy, involved field radiotherapy [IFRT] or involved site radiotherapy [ISRT]).

Materials & Methods. The clinical trial included 317 patients with stage II classical HL with supradiaphragmal lesions who have received chemo-radiotherapy in AM Granov Russian Scientific Centre of Radiology and Surgery Technologies from 1986 to 2015 (n = 301) and in SM Berezin International Institute of Biological Systems from 2014 to 2016 (n = 16). The mean age was 30.9 years (range 18–65); the study group included 107 men and 210 women. The diagnosis in all the cases was confirmed by immunomorphologic analysis. The treatment program included 2 to 6 cycles of ABVD regimen followed by CF (n = 153) or MF (n = 148) radiation therapy. The patients received mantle radiotherapy or IFRT with the cumulative dose of 30 to 40 Gy (2D planning, 237 patients) or ISRT with the cumulative dose of 30 to 40 Gy (3D planning, n = 80, CF only). The MF-regimen was administered only with 2D planning, mantle radiotherapy and IFRT. The CF-regimen was administered with 2D-planning (n = 89) with the same volume of radiation and 3D planning using conformal RT (3D-CRT) as ISRT with the cumulative dose of 30 to 36 Gy (n = 80). From the total of 80 patients 16 patients were treated with beam intensity modulation (IMRT) and 64 patients were treated without IMRT.

Results. The treatment response (both complete and partial remission) was reported in 235 (99.2 %) of 237 patients of 2D planning group. In 2 cases (0.8 %) a progression of disease was diagnosed. Out of 235 patients with remission 222 (94.5 %) had a complete remission and 13 (5.5 %) had a partial remission. Within the group treated with the conventional RT 19 (8.1 %) patients had recurrent disease. Overall 5- and 10-year survival (OS) was equal and accounted for 98.0 ± 1.4 %, the disease-free survival (DFS) was also equal between groups and accounted for 85.9 ± 1.3 %. The rate of 5- and 10-year OS in patients who received CF was 97.8 ± 1.7 %; the DFS rate for the same period was 85.0 ± 1.5 % with standard fractionation and 86.2 ± 1.6 % with MF (> 0.1). The total number of local radiation reactions and the number of radiation pulmonitis were significantly smaller with the exposure twice daily compared to CF at 2D planning and mantle irradiation. Decreasing the radiation volume from the mantle type to IFRT was shown to reduce the incidence of pulmonitis. The incidence of esophagitis remained the same with different fractionation and the irradiation volumes specified above. The results of the analysis proved the total absence of radiation pericarditis with both types of conformal RT with or without IMRT. No pulmonitis cases were observed with IMRT; the use of 3D-CRT and 2D-RT significantly increased the incidence of pulmonitis. The incidence of esophagitis within the CRT-group (n = 80) was 2 times lower compared to the conventional RT (22.5 % and 43.9 %; < 0.01).

Conclusion. The innovative technologies of radiation therapy allowed to reduce the incidence of early local radiation reactions. These technologies will be the basis for preventing severe late radiation complications that reduce the life expectancy and quality of life of patients with HL.

Keywords: Hodgkin’s lymphoma, radiotherapy, fractionation, 2D and 3D planning.

Received: September 16, 2017

Accepted: December 5, 2017

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The Use of Brentuximab Vedotin in Relapsed/Refractory Hodgkin’s Lymphoma in the Kransnodar Region

OD Serdyuk, DA Yaskul’skii

Clinical Oncology Dispensary No. 1 of the Krasnodar region, 146 Dimitrova str., Krasnodar, Russian Federation, 350040

For correspondence: Ol’ga Dmitrievna Serdyuk, 146 Dimitrova str., Krasnodar, Russian Federation, 350040; Tel.: +7(918)441-08-33; e-mail: 7-18@mail.ru

For citation: Serdyuk OD, Yaskul’skii DA. The Use of Brentuximab Vedotin in Relapsed/Refractory Hodgkin’s Lymphoma in the Kransnodar Region. Clinical oncohematology. 2018;11(1):50-3.

DOI: 10.21320/2500-2139-2018-11-1-50-53


ABSTRACT

The treatment of relapsed/refractory Hodgkin’s lymphoma (HL) remains to be a challenging issue. The morbidity of HL is reported to increase in the Krasnodar region. While considerable progress in the treatment of HL has been achieved, the relapse rate still remains high. The standard second-line treatment allows for the disease control in only half of cases of relapsed HL. Until recently, however, relapses after autologous hematopoietic stem cell transplantation (autoHSCT) could be treated only by polychemotherapy aimed at slowing the tumor growth. The use of anti-CD30 conjugated monoclonal antibodies and cytotoxic agent was shown to control the relapsed disease after high dose chemotherapy followed by autoHSCT. The present study provides pharmacological characteristics of brentuximab vedotin, its antineoplastic mechanism as well as the author’s own clinical experience in the management of a female patient with HL after autoHSCT.

Keywords: Hodgkin’s lymphoma, brentuximab vedotin, targeted therapy, relapse.

Received: November 25, 2017

Accepted: January 8, 2018

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REFERENCES

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Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives

KN Melkova, GD Petrova, NV Gorbunova, TZ Chernyavskaya, OP Trofimova

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

For correspondence: Kapitolina Nikolaevna Melkova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: frolov63@bk.ru

For citation: Melkova KN, Petrova GD, Gorbunova NV, et al. Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives. Clinical oncohematology. 2017;10(4):494–500 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-494-500


ABSTRACT

Hematopoietic stem cells transplantation is a current standard treatment for many oncohematological diseases. The milestone of any type of transplantation is the choice of conditioning regimen. This article presents the principles of classification of conditioning regimens in terms of myeloablativity and discusses the concepts of “autologous transplantation”, “high-dose chemotherapy supported by hematopoietic stem cells”, “allogeneic transplantation” and “immunotherapy”. Up-to-date uniform classification of conditioning regimens may serve an important prognostic component in assessing both the risks and efficacy of hematopoietic stem cells transplantation.

Keywords: conditioning regimens, allogeneic hematopoietic stem cell transplantation, autologous hematopoietic stem cell transplantation, total therapeutic exposure, acute leukemia, Hodgkin’s lymphoma, multiple myeloma.

Received: March 29, 2017

Accepted: July 8, 2017

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REFERENCES

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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)

EA Demina1, AA Leont’eva1, GS Tumyan1, YuE Ryabukhina1, OP Trofimova1, NV Volkova1, YuI Pryamikova1, VM Sotnikov2, VB Larionova1, EG Medvedovskaya1, EV Paramonova1, LV Manzyuk1, NA Probatova1, NV Kokosadze1, EA Osmanov1

1NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2Russian Scientific Center of Radiology and Nuclear Medicine, 86 Profsoyuznaya str., Moscow, Russian Federation, 117997

For correspondence: Prof. Elena Andreevna Demina, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-90-89; e-mail: drdemina@yandex.ru

For citation: 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 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-443-452


ABSTRACT

Aim. To assess the efficacy and toxicity of intensive 6 courses EACOPP-14 treatment with or without radiotherapy (RT) for advanced stages of Hodgkin’s lymphoma (HL).

Materials & Methods. From November 2009 to February 2015, 95 patients with advanced stages of HL (IIX–IIE, III–IV) aged between 17 and 50 years (median 29 years) were selected for the participation in the protocol ЛХМосква1-3. The study population consisted of 46.3 % men and 53.7 % women. The results of the treatment were assessed in 91 patients who have received more than 2 courses of EACOPP-14. The follow up period was at least 3 months after the receiving the therapy. Consolidation RT with a total dose of 30 Gy for residual tumor lesions and/or initially large tumors was performed after the chemotherapy.

Results. Complete remission was achieved in 82 (90.1 %) patients, partial remission in 2 (2.2 %), and the progression was observed in 7 (7.7 %) patients. The overall 4-year survival rate was 90.8 %, the progression-free survival was 88.2 %. The toxicity of the ЕАСОРР-14 program was slightly lower than that of 8 courses of ВЕАСОРРesc, and was comparable to the toxicity of other modifications of intensified ВЕАСОРР scheme. Hematological toxicity grade 3 and 4 was most commonly observed: leukopenia was observed after 64.9 % of courses, anemia — after 24 % of courses, thrombocytopenia — after 3.8 % of courses. The rate of infections did not singificantly differ and accounted for 24 %. The most frequent non-infectious complications were mucositis (21.1 %) and polyneuropathy (11.7 %). Complications resulted in the change of treatment in only 3 (3.01 %) of patients. The exclusion of bleomycine from the ЕАСОРР-14 program reduced the frequency of RT complications. Grade 3 pulmonitis developed in 4.5 % of cases, while radiation-induce pulmonary fibrosis verified by CT developed in 15.2 % of cases. The ЕАСОРР-14 6 courses program showed its high efficacy both with and without RT, high tolerance and the possibility of full administration for the majority of patients with the various stages of HL.

Conclusion. Current research showed the efficacy of treatment without RT for patients with advanced stages of HL with negative PET results and small (< 2.5 cm) residual tumors after intensive ЕАСОРР-14 program. This approach allowed to avoid a number of late treatment complications.

Keywords: Hodgkin’s lymphoma, advanced stages, intensive first-line chemotherapy.

Received: March 10, 2017

Accepted: June 23, 2017

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The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity

KD Kaplanov1,2,3, TYu Klitochenko1,3, AL Shipaeva1, MN Shirokova1, IV Matveeva1, NB Lavrishina1

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

2 Volgograd Medical Research Center, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

3 Volgograd State Medical University, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

For correspondence: Kamil’ Daniyalovich Kaplanov, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Klitochenko TYu, Shipaeva АL, et al. The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity. Clinical oncohematology. 2017;10(3):358–65 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-358-365


ABSTRACT

Background. Among the newly diagnosed patients with Hodgkin’s lymphoma (HL), the proportion of elderly patients account for 15–35 %. In > 60 age group the choice of antitumor treatment requires an more individualised approach compared to a younger population. The ABVD regimen is acceptable in terms of efficiency and hematological toxicity, but is associated with a high risk of bleomycine-induced pulmonary complications. In ≥ 60 age group the morbitity and mortality of pulmonary complications account for 24 % and 18 %, respectively.

Aim. We aimed to evaluate the efficacy of the IVDG regimen in comparison with ABVD by the principle of “non-inferiority”.

Materials & Methods. This single centre, prospective, controlled, randomised study was started in 2009. The study included all primary patients aged ≥ 60 years with verified HL, regardless of the number and severity of comorbidities. The ABVD regimen was administered in 17 patients, and 20 patients received IVDG. The median age in the ABVD and IVDG groups was 67 and 70 years, respectively. The advanced stages of HL were reported in 13 (65 %) patients on IVDG, and in 12 (71 %) patients on ABVD (p = 0.9). Both of the groups were comparable in terms of the prevalence of chronic heart failure and chronic obstructive pulmonary disease. The prevalence of ischemic heart disease was higher in the IVDG group (n = 16) compared to ABVD (n = 8) (p = 0.04).

Results. IVDG and ABVD groups did not differ in the frequency of complete (14 and 10) and partial (3 and 4) remissions. Differences in 5-year overall survival were insignificant: 49 % in the IVDG group, vs 22 % in ABVD group (p = 0.41). No infectious or hemorrhagic complications were observed in both groups. The incidence of drug-induced pulmonary fibrosis after treatment was significantly lower in the IVDG group (n = 0) vs ABVD group (n = 4; 24 %) (p = 0.004).

Conclusion. The IVDG regimen may be used as first line treatment for HL in the elderly patients, especially in those having cardiac or pulmonary comorbidities. Compared to ABVD the IVDG regimen had similar efficacy and more beneficial safety profile in terms of cardiovascular and pulmonary toxicity.

Keywords: Hodgkin’s lymphoma, elderly patients, comorbidity, chemotherapy.

Received: December 22, 2016

Accepted: March 5, 2017

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