[389] Phase II Study of R-CHOP Followed by ⁹⁰Y-Ibritumomab Tiuxetan in Untreated Mantle Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499. Session Type: Oral Session

Mitchell R. Smith, Lijun Zhang, Leo I. Gordon, James Foran, Brad Kahl, Randy D. Gascoyne, Ranjana Advani, Elisabeth Paietta, Edie Weller, Sandra J. Horning Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA; Biostatistics, Dana Farber Cancer Institute, Boston, MA, USA; Medical Oncology, Northwestern Univ, Chicago, IL, USA; Medical Oncology, University of Alabama - Birmingham, Birmingham, AL, USA; Medical Oncology, University of Wisconsin, Madison, WI, USA; British Columbia Cancer Agency, Vancouver, BC, Canada; Stanford University, Stanford, CA, USA; Our Lady of Mercy Cancer Center, Bronx, NY, USA

Background: As MCL has a continuous relapse pattern with current treatments, we designed a study to determine the safety and efficacy of the anti-CD20 radio-immunoconjugate,⁹⁰Y-ibritumomab tiuxetan (⁹⁰Y-RIT), following 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) induction. Methods: Patients (pt) with untreated stage II-IV MCL (CD20+, cyclin D1+) 18 yr with measurable/evaluable disease and adequate organ function were eligible. At 4-8 weeks after 4 cycles of R-CHOP, responding (CR/PR) and stable pt received 0.4 mCi/kg ⁹⁰Y-RIT. The primary endpoint was failure-free survival (FFS) and secondary objectives were evaluation of response and toxicity after R-CHOP and after ⁹⁰Y-RIT. The study design required 52 eligible pt to demonstrate a prolongation of FFS by 50% compared with R-CHOP alone (median FFS 16 mo, Howard et al., JCO 20:1288, 2002). Results: The characteristics of 56 eligible pt are: 73% male, median age 61 (33-83) yrs, 91% stage III/IV, 68% >1 extranodal site, 78% marrow-positive. IPI was 0-2 in 51%, 3-5 in 49%. Fifty-one (91%) pt received all treatment and best response (n=50) was 42% CR/CRu, 32% PR, 12% stable and 4% unevaluable, with an improvement in response in 16 pt after ⁹⁰Y-RIT. After ⁹⁰Y-RIT, 55% had grade 3/4 neutropenia with no febrile neutropenia and 45% had grade 3/4 thrombocytopenia with recovery at 12 weeks in 22/23 pt. Median follow-up (all pt) is 24.4 months. Median FFS for all 56 pt is 27 months with an estimated 71% FFS and 93% overall survival at 18 months. Among pt who completed all treatment and have been followed 1.5 yr (n=45), 33 remain failure-free and 12 have progressed (4 dead). Conclusions: ⁹⁰Y RIT after 4 cycles of R-CHOP in untreated MCL is safe and improves the number and quality of responses. These data suggest prolongation of FFS over that expected with R-CHOP alone. Consolidation of remission in MCL with 90Y-RIT shows potential as a strategy to prolong remission duration and is applicable to most pt with MCL. However, longer follow-up in needed to evaluate the durability of remissions achieved.
Abstract #389 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Non-Hodgkin Lymphoma|Radioimmunotherapy|Zevalin
Disclosure: Consultancy: Consulting Biogen Idec, Genentech. Research Funding: Biogen Idec, Genentech. Honoraria Information: Genentech. Membership Information: Biogen Idec, Genentech. Off Label Use: Use of Zevalin at approved dose and schedule, but for the non-approved use to consolidate remission in mantle cell lymphoma.

Monday, December 10, 2007 12:00 PM

Session Info:  Simultaneous Session: Lymphoma: Chemotherapy, excluding Pre-Clinical Models-Follicular and Mantle Cell Lymphoma (11:00 a.m.-12:30 p.m.)