Final results of phase I/II trial of vorinostat in combination with cyclophosphamide, etoposide, prednisone, and rituximab (R-CVEP) for elderly patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

8054 Background: Standard treatment of relapsed/refractory DLBCL in elderly patients who are not candidates for autologous stem cell transplantation (auSCT) has not been established. Cyclophosphamide (C), etoposide (E), prednisone (P) and procarbazine (CEPP) has been used by many clinicians based on limited data (Blood 76: 1293-98, 1990). Vorinostat (V) is a histone deacetylase inhibitor that is approved for relapsed cutaneous T-cell lymphoma and has activity in B-cell lymphomas. This trial defined the maximum tolerated dose (MTD) of V added to standard therapy and determined the response rate of this combination. Methods: Patients ≥age 60 with relapsed/refractory DLBCL not candidates for auSCT were enrolled on R-CVEP (R 375mg/m 2 IV, d1; C 600mg/m 2 d1 and 8, E 70mg/m 2 IV d1, 140mg/m 2 d2 and 3; V PO and Pred 60mg/m 2 PO d1-10) every 28 days for 6 cycles. In the phase I component V was administered at doses of 300mg/d or 400mg/d for 10 days. The phase I was a 3 + 3 design and the phase II a two stage design requiring 8/20 complete responses (CR) for expansion. Assessment of response utilized end-of-treatment positron emission tomography (PET) (JCO 25: 579-86, 2007). Quality of life (QOL) was measured with the FACT-Lym v.4. Results: 27 pts. were enrolled. 1 died before treatment. For 26 pts: median age 76 yrs. (69-88), 14 females and 12 males, baseline PS (ECOG) 1 (0-2). Median follow-up for survivors: 9.2 mo. Phase I: 6 pts. at 300mg/d (no dose-limiting toxicity-DLT), 6 pts. at 400mg/d (2 grade 3 neutropenia = DLT). MTD 300mg/d x 10d. For 20 pts. at V 300mg/m 2 (6 phase I + 14 phase II): 2 off study for toxicity, 1 withdrew consent, 6 CR (30%), 5 partial response (PR) (25%), 6 progressed (30%). Phenotypic overall responses (OR): germinal center (GC) 4/8 (2 CR), non-GC 6/10 (3 CR), transformed CLL 1/2 (1 CR). Median progression-free survival: 10 mo. QOL results will be presented. Conclusions: OR rate for V added to conventional chemotherapy and R was 55% (CR 30%, PR 25%) in relapsed/refractory DLBCL in elderly pts. not candidates for auSCT. This could provide a baseline for comparison with future clinical trials in this understudied population.