Abstract
In ARL, rituximab may slightly improve CHOP response but is associated with greater toxicity (
Proc Am Soc Hem102:1488, 2003
). We hypothesized that the addition of rituximab to DA-EPOCH may increase fractional tumor cell kill and allow fewer treatment cycles and lower immune suppression. Patients received DA-EPOCH-R (E=etoposide 50 mg/m2/d, O=vincristine 0.4 mg/m2/d and H=doxorubicin 10 mg/m2/d all CIV d 1–4 (96 hours); C=cyclophosphamide 750 mg/m2 IV d5; P=prednisone 60 mg/m2 PO qd d1–5 and R=rituximab 375 mg/m2 IV d1 and 5) with G-CSF. Prophylactic IT MTX x 6 was administered. HAART was discontinued before and recommenced after DA-EPOCH-R. Unlike our previous study of DA-EPOCH in ARL (BLOOD101:4653, 2003
) where the dose of C was lower and based on CD4 cell count, all patients on this study received full dose C on cycle 1 with subsequent reduction if the ANC nadir was < 500/mm3 for ≥ 2 days. Patients received 1 cycle beyond CR, based on CT and PET, for a minimum of 3 cycles. Characteristics of 21 patients include median (range) age 39 (9–61) years; IPI 3 (0–4); ECOG PS 2 (1–4); CD4 212 (0–674) cells/mm3 and HIV viral load 53100 (0– 286472) RNA copies/mL. Additionally, male sex 17 (81%); LDH> nl 15 (71); stage IV 15 (71%) and histology with diffuse large B-cell 9 (90%) and Burkitt’s lymphoma 2 (10%). The 18 patients who completed treatment (2 TE; 1 NE) received a median (range) of 3 (3–5) cycles. Responses are CR/CRu 15 (83%); PR 1 (6%) and NR 2 (11%). At 19 mos median follow-up, overall PFS and OS are both 77%, and both 90% in patients with CD4 > 100 cells/mm3. Treatment outcome of DA-EPOCH-R is similar to DA-EPOCH (CR 74% and PFS 73% at 53 months) but with significantly shorter treatment (median cycles 3 vs. 6). Toxicity on 57 cycles include ANC < 500/mm3 on 27 (47%); platelets < 50,000/mm3 on 15 (26%) and; fever/neutropenia on 20 (35%) cycles. DA-EPOCH-R produced a median (range) CD4 cell decrement of 64 (−541 to + 239) cells/mm3 compared to 189 (−973 to +19) with DA-EPOCH. Hematological toxicity is higher with DA-EPOCH-R compared to DA-EPOCH with ANC < 500/mm3 47% vs 30% and fever/neutropenia 35% vs. 13%, respectively, likely due to higher C dose intensity and/or rituximab. Other toxicities are similar. Abbreviated DA-EPOCH-R is equivalent to DA-EPOCH x 6 and appears to produce less CD4 cell loss. Accrual continues.
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