Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues

Background & Aims. At least one third of patients with diffuse large B-cell lymphoma (DLBCL) are resistant to first-line therapy. R-CHOP chemo-immunotherapy does not yield acceptable results in high-risk patients. Effectiveness of options based either on increasing the dose intensity or on including auto-HSCT into the first-line therapy was not supported by the results of controlled studies. With this background the present study focuses on options, issues and failures of first-line on the basis of long-term follow-up of DLBCL patient population in the Volgograd Region.

Materials & Methods. From 2004 to 2017 the population-based registry of the Hematology Department in the Volgograd Regional Clinical Oncology Dispensary included all 492 primary DLBCL patients: 235 (48 %) men and 257 (52 %) women aged 18 to 88 years. Mean and median age was 59 and 61 years, respectively. CHOP therapy was administered to 206 (42 %) patients, and 223 (45 %) patients received R-CHOP. Other regimens including NHL-BFM-90 and R-DA-EPOCH were used only in 63 (13 %) patients. Second- and third-line therapies were administered to 145 (30 %) and 54 (11 %) patients, respectively. Value of the International Prognostic Index (IPI) and immunomorphologic characteristics was determined by multivariate Cox regression analysis. Pharmacoeconomic aspect of first-line therapy failures was analyzed using Markov model.

Results. Improvement of DLBCL therapy effects with the use of R-CHOP chemo-immunotherapy is particularly obvious in the groups with favorable and intermediate prognosis with 5-year overall survival (OS) of 90 % and 69 %, respectively. R-CHOP results are not considered to be satisfactory in the high-risk group: 5-year OS was 38 %. Pharmacoeconomic analysis proves the advantage of chemo-immunotherapy strategy in comparison with the period before rituximab era in terms of the life years gained (LYG) and the incremental cost-effectiveness ratio (ICER). With respect to immunotherapy effects the most significant immunomorphologic parameter is bcl-2 tumor cell expression. In the group of patients with bcl-2 > 50 % 5-year OS was 61 % with median of 88 months, event-free survival (EFS) was 52 % with median of 62 months. In the group without bcl-2 expression above the threshold 5-year OS and EFS were 88 % and 75 %, respectively, medians were not achieved. With c-myc and bcl-2 coexpression EFS and OS appeared to be even worse: 5-year EFS was 29 % with median of 6 months, and 5-year OS was 31 % with median of 15 months.

Conclusion. The analysis of actual practice demonstrates the need for new options of first-line therapy for DLBCL high-risk patients and also for introducing new discriminating prognostic factors which include the IPI-independent ones.

• Kamil’ Daniyalovich Kaplanov Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российcкая Федерация, 400138; ГБУ «Волгоградский медицинский научный центр», ул. Рокоссовского, д. 1Г, Волгоград, Российcкая Федерация, 400081
• N.P. Volkov Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российcкая Федерация, 400138
• T.Yu. Klitochenko Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российcкая Федерация, 400138
• I.V. Matveeva Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российcкая Федерация, 400138
• A.L. Shipaeva Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российcкая Федерация, 400138
• M.N. Shirokova Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российcкая Федерация, 400138
• N.V. Davydova Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081 ; ГУЗ «Консультативно-диагностическая поликлиника № 2», ул. Ангарская, д. 114А, Волгоград, Российcкая Федерация, 400081
• E.G. Gemdzhian National Medical Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4а, Москва, Российская Федерация, 125167
• D.S. Abramov Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997 ; ФГБУ «НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России, ул. Саморы Машела, д. 1, Москва, Российская Федерация, 117997
• D.M. Konovalov Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997 ; ФГБУ «НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России, ул. Саморы Машела, д. 1, Москва, Российская Федерация, 117997
• G.L. Snigur Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081 ; ГБУ «Волгоградский медицинский научный центр», ул. Рокоссовского, д. 1Г, Волгоград, Российcкая Федерация, 400081
• N.A. Red’kina Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российcкая Федерация, 400138

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