A phase II study of gemcitabine, ifosfamide, and oxaliplatin (GIFOX) as upfront treatment for high-risk, non-anaplastic large cell, peripheral T-cell lymphomas.

Abstract

8564 Background: Patients (pts) with peripheral T/NK cell lymphomas (PTCL) and intermediate-high/high IPI risk have a 5-yr overall survival < 20%. Current chemotherapy is unsatisfactory while benefit of upfront autologous transplantation (ASCT) is limited by high pre-transplant progression rates and pts advanced age. We evaluated efficacy and stem cells (SCs)-mobilizing activity of a biweekly regimen of gemcitabine (G), ifosfamide (Ifo) and oxaliplatin (Ox) (GIFOX), as an upfront strategy ensuring fast cytoreduction and early ASCT access or an effective alternative to CHOP-like programs in transplant-inelegible pts. Methods: Six biweekly courses of GIFOX [G 1000 mg/m2 D1, Ox 130 mg/m2 D2, Ifo 5 g/m2 D2 as 24h infusion (fractionated over days 2-4 in pts>65 yrs), G-CSF DD 7-11] were planned for all pts, with SCs mobilization at course 3 in ASCT-eligible pts. Simon's minimax two-stage design was adopted with the primary and secondary endpoints of response rate (RR) and progression-free survival (PFS), respectively. Results: Thirty-four pts (median age 63 yrs, r 42-80) [PTCL, nos (n=16), AITL (n=7), extranodal NK/T-cell (n=5), SS (n=6)], with IPI score intermediate-high (62%) or high (38%) were accrued [stage IV: 71%; BM involvement: 38%; E-site >1: 47%; hi LDH: 71%; ECOG>1: 38%; B-symptoms: 44%]. A total of 172 courses was delivered (median 6, r 2-6). Only 5 pts received <4 courses, due to progression (n=4) or early death (n=1). Overall RR was 82% [95% CI, 66-92; 22 complete (CR) and 6 partial (PR) responses]. Twelve pts mobilized SCs (median CD34+ cells harvest: 4.36x106/kg) and 8 (7CRs,1PR) underwent ASCT, 6 to 13 weeks after the 6th course. Estimated 5-yr PFS was 48% (95%CI: 28-65); median PFS for non-transplanted pts was 15 mo.s. Estimated 4-yr disease-free survival was 58%. Relevant toxicities were G4 thrombocytopenia (13%), G4 anemia (23%), G3/G4 infection (29%/6%), G3 encephalopathy (6%). Conclusions: Response and survival rates of GIFOX in high-risk PTCL compared more than favorably to CHOP-based regimens. Effective cytoreduction and prompt access to ASCT were ensured, together with safe delivery of a full induction program to transplant-ineligible pts.