[643] 90Y-Ibritumomab Tiuxetan (Zevalin) Consolidation of First Remission in Advanced Stage Follicular Non-Hodgkins Lymphoma: First Results of the International Randomized Phase 3 First-Line Indolent Trial (FIT) in 414 Patients. Session Type: Oral Session
Anton Hagenbeek, Angelika Bischof-Delaloye, John A. Radford, Ama Rohatiner, Gilles Salles, Achiel Van Hoof, Barbara Putz, Michael Kunz, Franck Morschhauser UMC Utrecht/HOVON, Netherlands; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Christie Hospital, Manchester, United Kingdom; St. Bartholomews Hospital, London, United Kingdom; Centre Hospitalier Lyon Sud, Pierre Bnite, France; General Hospital St. Jan, Brugge, Belgium; Bayer Schering Pharma AG, Berlin, Germany; Hpital Huriez, Lille, France
Radioimmunotherapy is effective in patients with relapsed/refractory and newly diagnosed follicular non-Hodgkins lymphoma (FL). This study investigated the efficacy and safety of Zevalin consolidation in patients with advanced stage FL responding to first-line chemotherapy.
The concept tested was whether a single infusion of Zevalin would prolong progression free survival (PFS) in patients with (minimal) residual disease. Major inclusion criteria were: CD20-positive grade 1 or 2 FL; stage III or IV at diagnosis; normal peripheral blood cell counts; <25% bone marrow involvement; age 18 yrs, and CR/CRu or PR after first line chemotherapy determined by physical examination, CT scans and bone marrow biopsy.
From 8/2001 to1/2005, 414 patients were enrolled at 77 study centers in 12 European countries and Canada. After completing induction therapy, patients were randomized to receive either Zevalin (250 mg/m2 rituximab on day -7 and on day 0 followed on day 0 by Zevalin 0.4 mCi/kg; maximal dose: 32 mCi;[n=208]) or no further treatment [n=206]). The primary end point was prolongation of PFS, calculated from randomization, which was approximately 2 wks before Zevalin administration. Secondary end points were change of response status, ie, PR to CR/CRu and BCL2-JH PCR status from positive to negative; safety/tolerability and quality of life. Patient demographics were similar in both groups (Zevalin/control): males 48%/50%; median age 55/53 yrs; at diagnosis, stage III 35%/31%, stage IV 64%/66%; B-symptoms 22%/20%; response status after induction, PR 49%/47%; CR: 51%/53%. Induction therapies included: CVP n=106, CHOP (-like) n=188, fludarabine combinations n=22, chlorambucil n=39 and rituximab-chemotherapy combinations n=59.
With a median follow-up of 2.9 yrs, the median PFS increased from 13.5 (controls) to 37 mo (Zevalin; p<0.0001; HR 0.463). For patient subgroups in PR or CR after induction, median PFS was 6.3 vs 29.7 mo (p<0.0001; HR 0.304) and 29.9 vs 54.6 mo (p=0.01; HR 0.609), respectively. After Zevalin consolidation, 77% of patients in PR after induction therapy converted to CR; in total, 87% of patients were in CR(u), 76% in CR and 11% in CRu. Subgroup analyses based on induction treatment and outcome according to FLIPI will be presented.
Toxicity was primarily hematologic. Median platelet count nadir was 45x109/L; range 8-404x109/L) at wk 7 (5 wks post Zevalin); median neutrophil nadir was 1.0x109/L (range 0.02-6.6x109/L) at wk 8( 6 wks post Zevalin). Grade 3/4 infections occurred in 16 (8%) patients after Zevalin vs 5 (2%) in the control arm. So far, 11 patients have died, 5 in control arm (1 sepsis, 4 progressive disease); 6 in Zevalin arm (1 neutropenic sepsis after subsequent chemotherapy, 1 pancreas carcinoma, 1 AML, 3 progressive disease).
Conclusion: Zevalin consolidation of first remission in advanced stage FL is highly effective, resulting in a total CR(u) rate of 87% and prolongation of PFS by 2 yrs, with a favorable toxicity profile.
Abstract #643 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Lymphoma Therapy|Radioimmunotherapy|Zevalin
Monday, December 10, 2007 3:30 PM
Session Info: Simultaneous Session: Immunotherapy for Lymphoma, including Radio-Immunotherapy (3:30 p.m.-5:00 p.m.) |
