A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted R EPOCH Regimen

Background:High‐grade B‐cell NHL's are 200‐fold more common in seropositive as compared to seronegative patients. They have a higher incidence of extranodal involvement, advanced stage and chemoresistance. To add to the complexity, social stigma and financial constraints decrease the compliance to therapy. R‐EPOCH is designed to provide a balance between efficacy and safety. We report on our cohort of patients who were treated with this protocol.Aims:The primary objective was the 3‐year overall survival (OS), secondary objectives were response rates, the incidence of grade3/4 toxicities, dose intensity and correlation of OS with CD4 count, IPI, duration of HIV, Cyclophosphamide dose intensity (CDI).Methods:We analysed seropositive de‐novo high‐grade B‐cell NHL patients who were treated at Tata Memorial Centre from 2011 till 2015. Patients aged ≥18 years who had received at least 1 cycle were included in the analysis. Demographic features, HIV related details, histological diagnosis, disease characteristics, treatment details, response, toxicity and status, at last, follow up were recorded. Descriptive statistics were summarised, survival outcomes were analysed with Kaplan Meier method and impact of CD 4 count, CDI, IPI and duration of HIV on survival was assessed using log‐rank test.Results:A total of 40 patients(31males) with a median age of 40 years (24–65 years) were treated. B symptoms were present in 19(48%). The cohort comprised of DLBCL‐19 (48%), BL‐16(40%), High‐grade B‐Cell Lymphoma‐Unclassifiable‐4 (10%) and PBL 1 (2.5%). 16 (40%) patients had co‐morbidities, including co‐existent Hepatitis C in 5 and Hepatitis B in 2. HIV infection was detected at the time of lymphoma diagnosis in 18 (45%). The median CD4+ T cell count was 202 cells/mm3, 6 patients (15%) had count of <100/mm3. All patients received HAART while on chemotherapy. Performance status (ECOG) ≤2 was seen in 36(90%) patients. 38 (95%) had stage III/IV disease and bulky disease (defined as size ≥7 cm) was seen in 29(72%) patients. Extranodal involvement was seen in 36(90%) patients. Haemoglobin level ≤11 g/dL in 10(25%) patients (range‐ 8.2–15.6 g/dL), serum albumin <4 g/dL in 23(58%) patients, serum LDH ≥ upper normal limit −38 (95%) patients. At least 4 cycles of chemotherapy were administered to 35 (93%) patients, with 28 (70%) receiving 6 cycles. CNS prophylaxis was administered with intrathecal methotrexate (median number‐6) to 36(90%) patients. High dose methotrexate was given to 5 patients. Rituximab was not administered to 5 patients (3 due to CD4 count <100, 2 due to CD20 negativity). Responses were assessed using 18FDG PET‐CT scan with complete response‐32(80%), partial response‐1(3%), disease progression‐4(10%) and not evaluable‐ 4 (7%). Grade 3/4 toxicities were seen in 33(83%) patients, with febrile neutropenia‐26(65%), mucositis‐10(25%) and peripheral neuropathy in5(13%) patients. Out of the 210 cycles administered, there were 41(20%) episodes of hospitalization (duration ranged from 2–51 days). There were 11(28%) deaths (progression‐7, toxicity‐2, Not known‐2) and 7(18%) patients had progression (4‐ on treatment progression, 3‐ relapses). With a median follow‐up of 47 months, estimated 4‐year OS is 72% (Figure 1) and 4‐year disease‐free survival is 82%. There was no difference in survival based on IPI, CD 4+ T cell count, CDI or duration of HIV.Summary/Conclusion:R‐EPOCH is a highly effective regimen in seropositive high‐grade B‐cell lymphoma even in the presence of adverse features.image