Phase I Trial of Combination Therapy with ⁹⁰y Ibritumomab Tiuxetan and Gemcitabine in Patients with Non-Hodgkin's Lymphoma, Final Report.

Abstract 2753

Y⁹⁰-ibritumomab tiuxetan radioimmuotherapy (Y⁹⁰-RIT) is an effective therapy against CD20+ lymphomas approved for use in patients (pts) with relapsed/refractory low grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), as well as consolidation of first remission low grade NHL. Gemcitabine (Gem) also is active against NHL and is a potent radiation sensitizer. We conducted a phase I trial to assess the safety of concomitant administration of Y⁹⁰-RIT and G in patients with NHL. Eligible pts had any histologic subtype of recurrent CD20+ NHL (not candidates for potentially curative options) and met standard Y⁹⁰-RIT criteria: platelets 150,000/ul; < 25% bone marrow involvement by lymphoma; prior radiation to <25% of bone marrow and no prior bone marrow or stem cell transplant. Initially, nine pts in three cohorts were treated with 250 mg/m² of Gem IV on days 1 and 8 of the Y⁹⁰-RIT treatment program (rituximab + ¹¹¹In-ibritumomab day 1 and rituximab + Y⁹⁰ ibritumomab day 8), with Y⁹⁰-RIT at 0.2, 0.3 or 0.4 mCi/kg respectively. We confirmed that a standard Y⁹⁰-RIT dose of 0.4 mg/kg can be safely administered with Gem at 250 mg/m². In subsequent cohorts, escalating doses of Gem were used according to a Bayesian based system. Response evaluation was by CT scan criteria (IWG JCO 1999). Between 2004–2012, twenty pts were treated (10 follicular (FL), 3 marginal zone (MZL), 7 diffuse large B-cell (DLBCL) lymphomas). Median age is 71.5 (range 55–82). The median number of prior treatments is 3 (range 1–6). Gem doses ranged from 250 mg/m² to the maximum planned dose of 800 mg/m² on days 1 and 8. One DLT occurred (thrombocytopenia) and MTD was not reached. Treatment-related toxicities consisted of grades 3 (N=11) and 4 (N = 2) neutropenia, grade 3 (N=11) leukopenia, grades 3 (N=14) and 4 (N=8) thrombocytopenia. One grade 3 infection occurred, unrelated to study drugs. All pts recovered counts to ≤ grade 1 by week 12. The only grade 3 non-hematologic toxicity was elevated bilirubin in 1 and increased GGT in 2 pts. Best responses seen include: 3 CR/CRu, 7 PR, 4 SD, 4 PD and 2 patients still in follow up. Median PFS for all patients is 192 days. Median PFS for all non-DLBCL histologies (10 FL and 3 MALT) is 202 days and for DLBCL is 77 days.