Frontline R-EPOCH in HIV-infected patients with non-Hodgkin’s lymphoma
Ivan V. Tsygankov, Marina O. Popova, Yulia A. Rogacheva, Kirill V. Lepik, Yury R. Zalyalov, Lilia V. Stelmakh, Ivan S. Moiseev, Sergey N. Bondarenko, Natalia B. Mikhaylova, Vadim V. Baykov, Boris V. Afanasyev
Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
Contact: Dr. Marina O. Popova
Despite widespread use of antiretroviral therapy (cART), risk of cancer, including non-Hodgkin’s lymphomas (NHL) remains high in HIV-infected patients. The use of cART and possibility of its combination with chemotherapy (CT), as well as supportive care made positive changes in management of HIV-associated lymphomas. Immune prevention with cART has changed therapeutic approach to HIV-associated lymphoma, allowing the use of aggressive treatment strategies. The aim of our study was to estimate that R-EPOCH is safe and effective regimen in patients with HIV-related NHL.
Patients and methods
Thirty-two patients with HIV-related NHL (the study group) were treated since 2016 at the R. Gorbacheva Institute of Children Oncology, Haematology and Transplantation with 24-hour infusion of drugs, according to R-EPOCH regimen. The data of non-HIV-infected patients with NHL who received R-EPOCH therapy at the same period of time (control group, n=18) were also collected, in order to compare efficacy and safety of the regimen (2:1 ratio). Most patients (74%) were diagnosed with diffuse large B-cell lymphoma. The patients with plasmablastic lymphoma (PbL) received a modified chemotherapy (ChT): vincristine was replaced by bortezomib. This concerned two PbL patients from the study group, i.e., one patient received 6 courses of ChT, the second patient was treated by 2 ChT rounds. One PbL patient in the control group received 3 courses of ChT. Some patients with HIV-associated NHL (n=15) received two injections of rituximab per a course of ChT (day 1 and day 5 of each cycle). Virological evaluation of the patients before ChT showed that HIV viral load was undetectable (<50 copies/ml). The median number of CD4+ cells was 255 cells/mcl (50-680). 100% of HIV -infected patients received cART, with respect to possible drug interactions. The median follow-up was 19 (3-44) months in both groups. Objective response, toxicity, overall survival (OS), progression-free survival (PFS) were assessed during 24 months from the start of R-EPOCH regimen. Effectiveness of ChT was estimated using PET CT of the whole body and CT. Common Terminology Criteria for Adverse Events (CTCAE 4.0) were used to estimate toxicity. Kaplan-Meier method was used for OS and PFS analysis.
Objective response rate (ORR), i.e. complete remission (CR) + partial remission (PR), was 80% after finishing the ChT, CR comprised 42%. ORR in the study group was 87.5% (CR, 46.8%); in control group, 66.6% (CR, 33.3%). Toxicity assessed by CTCAE scale in both groups was also assessed. Hepatotoxicity in the study group was higher, probably, due to the presence of concomitant viral hepatitis in the group of patients with NHL associated with HIV infection. Overall survival (OS) for both groups (n=50) within 24 months following the ChT with continuous 24-hour infusion of drugs according to the R-EPOCH scheme was 74%. In the group of patients with HIV (study group) it comprised 67.7% against 84.2% among the control group of patients without HIV infection (p=0.182). Progression-free survival in total lymphoma group was 58.0%, being 51.6% among patients with HIV infection, and 68.4% in the control group (p=0.287).
ORR level was 87.5% in patients with HIV-associated lymphoma and 66.6% in patients without HIV. Toxicity rate did not differ between these groups. The 2-year OS from the start of ChT for the patients with HIV-associated lymphoma was 67.7%, and progression-free survival was 51.6%, showing no significant difference from the patients without HIV. These data confirm general safety and efficacy of R-EPOCH regimen in HIV-infected patients, being comparable with those in the group without HIV infection.
HIV-related lymphoma, NHL, chemotherapy, overall survival, toxicity, HIV status.