In ARL, the addition of Rituximab (R) to CHOP chemotherapy may improve tumor response but the benefit may be offset by increased infectious deaths in patients with low CD4 cell counts (

Kaplan et al. Blood2005;106:1538
). We hypothesized that R with EPOCH will improve tumor kill, allow fewer chemotherapy cycles and reduce toxicity. Patients received EPOCH-R (in mg/m2/d etoposide 50, vincristine 0.4 and doxorubicin 10 all CIV d 1–4; and in mg/m2 cyclophosphamide 750 IV day 5, prednisone 60 po days 1–4 and rituximab 375 IV d 1, 5; and G-CSF sc d 6–15). Prophylactic IT MTX x 6 was administered and HAART was discontinued on all cycles. Cyclophosphamide was adjusted based on absolute neutrophil count (ANC) nadir. Response was assessed by CT and PET and patients received 1 cycle beyond CR for a minimum of 3 cycles. Characteristics of 30 enrolled patients: median (range) age 41 (9–61) years; IPI 3 (0–4); ECOG PS 1 (1–4), CD4 count 213 (0–674) cells/mm3; HIV viral load 55,900 (0–6,080,000) RNA copies/mL; male sex 25 (83%); LDH > N 22 (73%); stage IV 20 (67%) and histology DLBCL 26 (87%) and Burkitt lymphoma 4 (13%). Of 28 evaluable patients (2NE), median (range) cycles given is 3 (3–5) with CR/CRu in 25 (89%) and PR in 1 (3%) patients. All 4 patients with Burkitt lymphoma are in continuous remission. At 35 months median potential follow-up, PFS and OS are 80% and 65%, respectively. For patients with CD4 > and < 100 cells/mm3 OS is 93% and 28%, respectively. IPI did not impact OS and PFS. We assessed the predictive value of early (after cycle 2 or 3) PET scanning on subsequent relapse. This was evaluated in 23 patients in follow-up. 0 of 13 patients with a negative PET study progressed (100% negative predictive value) whereas 2 of 10 patients with a positive PET progressed (20% positive predictive value). One death from MAI occurred on treatment and toxicity over 91 cycles of therapy included fever/neutropenia on 27 (30%), ANC < 500/mm3 on 36 (40%), and platelets < 50,000 on 21 (23%) cycles. EPOCH-R was associated with less CD4 loss - median 128 cells/mm3 (range +154 to −639) compared to EPOCH alone (median 189 cells/mm3 (range +19 to −973)(
Little et al. Blood2003;101:4653
). Abbreviated EPOCH-R is highly effective with acceptable tolerability in ARL and enables the administration of fewer treatment cycles (median 3 versus 6). Patients with CD4 < 100/mm3 have good tumor control with EPOCH-R with a PFS of 61% at 35 months, but survival continues to be limited by HIV-associated complications. In contrast, patients with high CD4 counts > 100/mm3 have an extremely favorable outcome with EPOCH-R. Albeit limited data, EPOCH-R was effective in all 4 patients with Burkitt lymphoma. PET scanning has a high negative but low positive predictive value for subsequent relapse. Accrual continues.

Figure 1
Figure 1.
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Figure 2
Figure 2.
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Topics:
antiretroviral therapy, highly active, burkitt's lymphoma, epoch protocol, lymphoma, aids-related, rituximab, positron-emission tomography, neoplasms, chemotherapy regimen, cyclophosphamide, follow-up

Disclosures: EPOCH-R agents are ot all approved for HIV associated lymphoma.

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2006, The American Society of Hematology
2006
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