Antiretroviral Therapy Has Equalized Presentations and Short-Term Outcomes Between HIV+ and HIV- Lymphoma Patients in Lilongwe, Malawi
Authors: Gopal Satish , Fedoriw Yuri D. , Montgomery Nathan , Moses Agnes , Nyasosela Richard , Mlombe Yohannie , Varela Carlos , Mzumara Suzgo , Chikasema Maria , Itimu Salama , Chimzimu Fred , Kampani Coxcilly , Krysiak Robert , Richards Kristy L. , Shea Thomas C. , Liomba George 
Published: November 2019

Abstract
Introduction. There are scarce prospective data for lymphoma patients in sub-Saharan Africa since antiretroviral therapy (ART) scale-up began. We report early data from the Kamuzu Central Hospital (KCH) Lymphoma Study in Lilongwe,Malawi. KCH is the cancer referral center for Malawi’s northern and central regions.
Methods. The KCH Lymphoma Study is a prospective observational cohort study initiated in June 2013. All diagnoses are pathologically confirmed using core biopsies or cell blocks from fine needle aspirates, supported by immunohistochemistry and weekly telepathology consultation between pathologists in Malawi and the US. Adult patients with confirmed lymphoma receive a comprehensive baseline evaluation including standardized staging. Patients undergo longitudinal follow-up with active tracing and transportation reimbursement to promote adherence to care. Response is assessed using standardized criteria incorporating physical exam, chest x-ray, and abdominal ultrasound. For these analyses, we focused on adults ≥18 years enrolled from June 1, 2013 until May 31, 2014. Chemotherapy protocols are standardized, and HIV+ patients receive ART concurrently with chemotherapy.
Results. Seventeen of 38 (45%) of patients with lymphoma were HIV+. Baseline characteristics for HIV+ and HIV- patients were similar although HIV- patients presented with bulkier disease (median 10 vs 6 cm, p=0.027, Table 1). Among HIV+ patients, 82% were on ART for a median 22.5 months before lymphoma diagnosis (range 0.2-98.8). Median CD4 was 178 cells/µL and 53% had suppressed HIV RNA <400 copies/mL. Thirty-one patients were treated with first-line CHOP (15 HIV+, 16 HIV-; 30 NHL, 1 HL). Five HL patients received first-line ABVD, 1 CLL patient did not require treatment for Rai Stage I disease, and 1 CLL patient received CVP. Patients treated with CHOP received a median 5 cycles (range 1-8). Among 14 of 31 patients receiving <6 CHOP cycles, reasons for stopping were death (n=8), progression (n=1), toxicity (n=3), and social (n=2). Overall survival 6 months after CHOP initiation was 61% (95% CI 38-78%), with no significant differences between HIV+ and HIV- patients (Figure 1).
Conclusions. Early experience in Malawi suggests ART has had equalized presentations and outcomes between HIV+ and HIV- lymphoma patients. CHOP can be safe, effective, and feasible in our setting for HIV+ and HIV- patients in the ART era. Among HIV+ patients, ART use, CD4 count, and HIV RNA at lymphoma diagnosis are comparable to contemporary US HIV+ lymphoma cohorts. Outcomes can be further improved through community education, better supportive care, protocol-based treatment, and incorporation of newer agents.
Table 1. Characteristics of adult lymphoma patients from June 2013-May 2014 in Lilongwe, Malawi. HIV- (n=21) HIV+ (n=17) P value Age (years), median (range) 45.6 (15.8-77.4) 47.2 (22.4-62.6) 0.51 Male, n (%) 16 (76.2%) 10 (58.8%) 0.31 Body mass index (kg/m2), median (range) 21.3 (16.2-28.0) 20.4 (16.0-31.2) 0.99 Histology 0.21 Aggressive B-cell lymphoma NK/T-cell lymphoma Plasmablastic lymphoma Chronic lymphocytic leukemia Non-Hodgkin lymphoma unspecified Hodgkin lymphoma 9 1  1 6 4 12  1 1 1 2 B symptoms, n (%) 18 (85.7%) 12 (70.6%) 0.69 Largest lymph node mass (cm), median (range) 10 (5-20) 6 (2-16) 0.027 Performance status ≥2 10 (47.6%) 4 (23.5%) 0.18 Stage III/IV, n (%) 12 (57.1%) 10 (58.8%) 1.00 White blood cells (103/µL), median (range) 6.8 (2.1-45.7) 5.7 (3.0-17.0) 0.23 Absolute neutrophil count (103/µL), median (range) 2.9 (0.5-29.9) 2.6 (1.0-5.1) 0.19 Hemoglobin (g/dL), median (range) 11.0 (4.4-14.3) 11.6 (5.7-15.1) 0.46 Platelets (103/µL), median (range) 290 (25-725) 190 (101-764) 0.15 Albumin (g/dL), median (range) 3.3 (1.1-4.2) 3.5 (2.1-4.8) 0.78 Lactate dehydrogenase (IU/L), median (range) 321 (134-1,080) 307 (177-2,939) 0.85 Bone marrow involvement, n (%) 2/18 (11.1%) 2/13 (15.4%) 1.00 ≥2 extranodal sites 5 (23.8%) 3 (17.6%) 0.71 Hepatitis B surface antigen positive, n (%) 1/15 (6.7%) 4/15 (26.7%) 0.33 Antiretroviral therapy at enrollment Duration (months), median (range) 14 (82.4%) 22.5 (0.2-98.8) CD4 (cells/µL), median (range) 178 (55-1,288) HIV RNA (log10copies/mL), median (range) 1.8 (ND->7.0) HIV RNA <400 copies/mL, n (%) 9 (52.9%)
ND=not detected.
Figure 1. Overall survival for 31 adult lymphoma patients treated with CHOP in Lilongwe, Malawi during the 6 months after treatment initiation. Figure 1. Overall survival for 31 adult lymphoma patients treated with CHOP in Lilongwe, Malawi during the 6 months after treatment initiation.

Disclosures
Shea: CALGB/Alliance: CALGB Board of Directors Other.