Response-adapted therapy with infusional EPOCH chemotherapy plus rituximab in HIV-associated, B-cell non-Hodgkin's lymphoma

Joseph A Sparano, Jeannette Y Lee, Lawrence D Kaplan, Juan Carlos Ramos, Richard F Ambinder, William Wachsman, David Aboulafia, Ariela Noy, David H Henry, Lee Ratner, Ethel Cesarman, Amy Chadburn, Ronald Mitsuyasu, Joseph A Sparano, Jeannette Y Lee, Lawrence D Kaplan, Juan Carlos Ramos, Richard F Ambinder, William Wachsman, David Aboulafia, Ariela Noy, David H Henry, Lee Ratner, Ethel Cesarman, Amy Chadburn, Ronald Mitsuyasu

Abstract

Four cycles of rituximab plus CHOP chemotherapy is as effective as 6 cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with HIV-associated DLBCL and high-grade lymphoma treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy. 106 evaluable patients with HIV-associated DLBCL or high-grade CD20-positive non-Hodgkin's lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. 64 of 106 evaluable patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms. The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) because a CR was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with HIV-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036.

Figures

Figure 1.
Figure 1.
Consort diagram.
Figure 2.
Figure 2.
Kaplan-Meier estimates of outcomes in patients achieving complete response to response-adapted EPOCH chemotherapy, stratified by number of treatment cycles. (A-C) Patients are stratified into two groups: a group that received four or fewer cycles of EPOCH chemotherapy and a group that received five or six cycles. Estimates are shown for event-free survival (A), time to progression (B) and overall survival (C).

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