CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

Abstract

There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV.

Mature outcomes and prognostic indices in diffuse large B‐cell lymphoma in Malawi: a prospective cohort

“…KCH is the referral hospital for the central and northern regions of Malawi, with a catchment area of around nine million people. For this report, we included participants ≥18 years of age with newly diagnosed DLBCL or high‐grade B‐cell NHL, not otherwise specified (B‐NHL, NOS), enrolled between June 2013 and May 2017 (Gopal et al , ). We excluded participants with DLBCL transformed from prior low‐grade lymphoma.…”

“…All participants were followed until death, loss to follow‐up, or administrative censoring on 30 September 2017. The full protocol is described elsewhere (Gopal et al , ). Briefly, all diagnoses were pathologically confirmed using tissue biopsy and immunohistochemistry with real‐time evaluation in weekly telepathology conferences, involving clinicians and 2–5 pathologists in the United States and Malawi who rendered a consensus opinion.…”

“…Patients underwent comprehensive baseline clinical and laboratory evaluation, as described previously (Gopal et al , ). Staging was completed by physical examination, chest x‐ray, abdominal ultrasound and bone marrow biopsy.…”

“…We previously reported early experience with baseline characteristics and outcomes for all aggressive NHL from the Kamuzu Central Hospital (KCH) Lymphoma Study, a prospective cohort of lymphoproliferative disorders in Malawi (Gopal et al , ). Here, we report the more deeply characterized, four‐year experience of baseline characteristics, tumour immunophenotypes, treatment course, outcome, and prognostic factors specifically for DLBCL, from the largest and most mature prospective longitudinal cohort in SSA.…”

HIV-associated malignancies in sub-Saharan Africa

“…Despite availability in LMIC of generic chemotherapy drugs which remain key components of NHL treatment even in high-income countries, stock outs are common, supportive care is limited including often absent hematopoietic growth factors, infusional and higher-intensity regimens are often impractical, infectious complications during chemotherapy and anti-infective prophylaxis strategies are poorly defined, and newer non-cytotoxic agents including rituximab are often not available. In Malawi, HIV-infected patients with aggressive NHL present with advanced bulky disease and poor performance status, although interestingly with less tumor bulk and shorter symptom durations than HIV-negative patients, perhaps reflecting primary care and referral networks established for HIV which are absent for HIV-uninfected populations [50*]. With appropriate monitoring and dose adjustment, even unselected HIV-infected patients can be treated with standard chemotherapy (CHOP; cyclophosphamide, doxorubicin, vincristine, prednisone), with comparable treatment intensity to HIV-negative patients, reasonably good outcomes, and deaths primarily related to relapsed/refractory NHL, although treatment-related mortality is also considerable.…”