Phase II Study of Hyper-CVAD with Pegylated Liposomal Doxorubicin Alternating with Methotrexate and Cytarabine (HCVIDD/MA) in Patients with Newly Diagnosed T- and NK-cell Lymphoma (T/NKCL).

8538 Background: Prognosis of T/NKCL is poor after standard CHOP therapy. To prospectively evaluate the role of dose intensified chemotherapy, we conducted a phase II trial of HCVIDD/MA in patients with newly diagnosed T/NKCL. Methods: Eligible patients were adults with newly diagnosed untreated T/NKCL excluding ALK positive ALCL. Patients received HCVIDD/MA every 21 days for up to eight cycles. In this trial, pegylated liposomal doxorubicin at 25mg/m2was used instead of conventional doxorubicin. Results: Fifty-three patients were enrolled (PTCL-NOS: 24, AITL: 7, Systemic ALK negative ALCL: 7, HSTL: 7, extranodal NKCL: 5, Others: 3). The median age of patients was 54 (range 20-72). Eighty-five percent of the patients were in advanced stage, 32% had bone marrow involvement and 43% had IPI score > 2. The median cycle number of treatment given was five. Only 5 of 53 patients (9%) received seven or more cycles primarily due to prolonged cytopenias. Of 47 patients who were eligible for response evaluation, the overall response rate was 66% with complete response rate of 57%. Six patients (11%) underwent consolidative autologous stem cell transplant at treating physician's discretion. Median progression free survival (PFS) of all patients was 8.1 months. With the median follow-up time of 83 months, five-year PFS and overall survival (OS) rates were 22% and 49%, respectively. The patients with extranodal NKCL had shorter PFS (all 5 progressed < 13 months) than other types. Patients with HSTL had slightly longer PFS (median 49 months) than other types. There was no significant difference in PFS or OS by treatment cycles beyond five and by consolidative ASCT. Grade3/4 anemia, neutropenia and thrombocytopenia were observed in 66%, 74% and 79%, respectively. Of note, 11 patients (21%) were taken off study due to thrombocytopenia with median of 5 cycles. Conclusions: HCVIDD/MA for the first line treatment of T/NKCL showed response rate and survival outcome similar to previously reported those with conventional CHOP, and was associated with higher hematologic toxicities. (clinicaltrials.gov identifier: NCT00290433) Clinical trial information: NCT00290433.