Long-Term Outcome of AIDS-Related Lymphoma Treated with Abbreviated Cycles of EPOCH-RR: A Prospective Study of 40 Patients

We hypothesized that the addition of rituximab to EPOCH chemotherapy could improve tumor kill, allowing delivery of fewer cycles of treatment and therefore reducing toxicity. Patients received EPOCH-RR (in mg/m²/d – etoposide 50, vincristine 0.4 and doxorubicin 10 all CIV d 1–5; cyclophosphamide 750 mg IV d 5; prednisone 60 po days 1–5 and rituximab 375 IV d 1,5 and G-CSF sc d 6–15) every 21 days. Prophylactic IT methotrexate was administered and HAART was suspended during therapy. Cyclophosphamide was adjusted based on absolute neutrophil count (ANC) nadir. Response was assessed by CT and FDG-PET scan and patients received 1 cycle beyond CR for a minimum of 3 cycles. Characteristics of 40 enrolled patients are: median (range) age 42 (9–60) years; IPI 3 (0–4); ECOG PS 1 (1–4), CD4 count 222 (0–835) cells/mm³; HIV viral load 34,766 (0–6,080000) RNA copies/mL; male sex 35 (88%); LDH > N 27 (68%); stage IV 27 (68%) and histology diffuse large B-cell lymphoma (DLBCL) 32 (80%) and Burkitt lymphoma (BL) 8 (20%). Of 38 evaluable patients (2NE), median (range) number of cycles given is 3 (3–5) with CR/CRu in 35 (92%) and PR in 1 (3%) patients. At 4 years median follow-up, PFS and OS are 86% and 70%, respectively. Eight patients with BL are in continuous CR. For patients with CD4 > and < 100 cells/mm³, PFS is 96% and 69%, respectively. IPI did not impact OS and PFS. Early PET scanning (after cycle 2) had a high negative predictive value (100%) but low positive predictive value (20%). Fever/neutropenia occurred on 30%, ANC < 500/mm³ on 40%, and platelets < 50,000/mm³ on 23% of cycles. EPOCH-RR was associated with less CD4 loss - median 128 cells/mm³ (range +154 to −639) compared to historical data with EPOCH alone (median 189 cells/mm³ (range +19 to −973). Patients with CD4 < 100/mm³ had good tumor control, but OS was only 31% due to late deaths from advanced AIDS. Patients with CD4 counts > 100/mm³ had an extremely good PFS and OS. The addition of rituximab did not appear to cause serious infection related complications or deaths. However, one treatment-related death occurred from complications of mycobacterium avium intercellulare. Abbreviated EPOCH-RR is highly effective and tolerable in ARL and enables the administration of fewer treatment cycles (median 3 versus 6). PET scanning has a very high negative but low positive predictive value for subsequent relapse, possibly due to HIV associated PET changes. Accrual continues.