Comparative evaluation of the effectiveness of primary treatment regimens in patients with classical Hodgkin’s lymphoma from the group of unfavorable prognosis

Abstract

Objective. Comparative evaluation of the effectiveness and toxicity profile of intensified chemotherapy regimens BEACOPP escalated (esc.), BEACOPP-14 and EACOPP‑14 in primary patients with classical Hodgkin’s lymphoma of an unfavorable prognostic group.Materials and methods. The study included 149 patients: 84 women (56 %) and 65 men (44 %) with a newly diagnosed classic Hodgkin’s lymphoma, who received antitumor treatment in the Department of high-dose chemotherapy with a bone marrow transplantation unit at the Р. A. Hertzen Moscow Oncology Research Institute from 2006 to 2018. The median age was 31 years (17–69). The majority of patients were diagnosed with Hodgkin’s lymphoma nodular sclerosis (88.6 %). All patients belonged to an unfavorable prognostic group, despite the fact that more than 1/3 of them had local stages of the disease. The most frequent adverse factors identified in the majority of patients were: massive lymph node lesion (bulky disease) – in 111 patients (74.5 %), B-symptoms – in 84 (56.4 %), increased erythrocyte sedimentation rate – in 55 (36.9 %), extranodal lesion – in 105 (70.5 %), including bones and bone marrow – in 10 (6.7 %) and 14 (9.4 %), respectively. Antitumor treatment was performed under the BEACOPP program in the following modifications: BEACOPP‑14 – 94 (63.1 %), EACOPP-14 – 32 (21.5 %), BEACOPP-esc. – 23 patients (15.4 %). Consolidating radiotherapy was performed in the majority of patients – 132 (88.6 %).Results. After the chemotherapy, remission of the disease was achieved in 141 patients (94.6 %), a complete response was in 101 of them (67.8 %). The immediate antitumor effect was more expressed when using the program BEACOPP‑14 (in 72.3 %), compared to EACOPP‑14 and BEACOPP-esc. (in 59.4 % and 60.9 %, respectively).Chemotherapy resistance was observed in 8 patients (5.4 %). Chemotherapy results were improved in combination with radiation therapy in 40 patients (26.8 %). After the end of chemoradiotherapy, complete remissions were achieved in more than 93.6 % of patients. Relapses occurred in 8 patients: early – in 3 (2.1 %) and late – in 5 (3.5 %). Four patients died (2.7 %): 1 – from disease progression, 2 – from resistant relapse, and 1 patient from other causes.With a median follow-up of 46 months, the 5-year overall survival rate was more than 93.7 %, event-free-more than 83 %, and relapse-free – 90.3 % or more. When evaluating long-term treatment results depending on the induction chemotherapy program, the outcome was better when using the BEACOPP-esc. in comparison with EACOPP‑14 and BEACOPP‑14. The most frequent myelotoxic complication – more than 90 % – on all chemotherapy programs was deep leukopenia. Thrombocytopenia III–IV degree developed more often on the BEACOPP-esc. (in 52.2 %), severe anemia – on EACOPP‑14 (in 44 %). Among infectious complications, mucositis prevailed and was most often observed on BEACOPP-esc. (in 74 %). Febrile neutropenia and herpetic infection developed less frequently, mainly in the BEACOPP-esc. and EACOPP‑14 program. Another serious complication was pneumonia, which was more frequently reported during BEACOPP‑14 (18.1 %). Secondary tumors, as a later complication, were less likely to be detected in the treatment program BEACOPP‑14 (1 %), compared to BEACOPP-esc. and EACOPP-14 (4.3 % and 3.1 %, respectively).Conclusion. All modifications of the BEACOPP program showed good direct effectiveness. However, the best long-term results, despite slightly more expressed toxicity, were noted on the BEACOPP-esc. program.