Rituximab plus gemcitabine, ifosfamide, oxaliplatin (R-GIFOX) as salvage therapy for recurrent Hodgkin lymphoma

Abstract

8579 Background: Gemcitabine (G), ifosfamide (Ifo), oxaliplatin (Ox) and rituximab (R) have been accounted of cross-synergy in preclinical and early clinical studies in Hodgkin lymphoma (HL). We assessed activity, toxicity and stem cells (SCs) mobilizing capacity of a bi-weekly salvage combination with these agents in HL recurring after conventional or high dose therapy (HDT). Methods: Patients were scheduled to receive 3 R-GIFOX courses followed by SCs mobilization and HDT if elegible for autologous transplantation (ASCT) or 3 more courses if not. R-GIFOX consisted of R 375 mg/m2 D1, G 1000 mg/m2 D2, Ox 130 mg/m2 D3 and Ifo 5 g/m2 D3, as a 24-h single infusion, G-CSF 5 mcg/kg/d DD 7–11 (10 mcg/kg/d, 3rd course until SCs mobilization). Results: Twenty-one patients (median age 33 yrs, r 22–64) with relapsed (n = 16) [post-ASCT (n=6), <12 mo.s (n=7), > 12 mo.s (n=3)] or primary progressive (n = 5) HL, were prospectively accrued. Ten patients (48%) had received ≥ 2 previous CHT lines and 15 (78%) had GHLSG recurring HL prognostic score ≥ 2. Eighty-three total courses were delivered (median 3, r 3–6). CTCAE v3.0 G4 thrombocytopenia occurred in 18% of courses, G4 infection in 11%. Ifosfamide was withdrawn at the 4th course in 2 patients, both aged 64 yrs, due to tachyarrhythmia and encephalopathy. Actual dose intensity of the first 3 courses was 82%, 86%, 92 % for G, Ifo and Ox, respectively. The overall response according to FDG-PET/IWC criteria after 3 courses was 86%, with 2 partial and 16 complete responses (CRs) (76%; CR=10, CRu=6). Four CRs were achieved among the 6 patients with post-ASCT relapses. Eight of 14 eligible patients had effective CD34+ cells harvest [median 4,35 × 106/kg (r 2,91–11.45)] and proceeded to subsequent ASCT. Five ’bad mobilizers’ had previously undergone radiation therapy (n=3) and radioimmunotherapy (n=2). At 42 mo.s. Failure Free Survival was 57%. At a median f.u. of 12 mo.s for CRs, Disease Free Survival was 79% in patients eligible for ASCT and 41% in those unfit treated with additional R-GIFOX. Conclusions: R-GIFOX retains an attractive therapeutic potential in recurring HL, enabling pre-ABMT cytoreduction and mobilization, and also a safe delivery of a full salvage program to patients unfit for HDT. No significant financial relationships to disclose.