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Mature Results of BEAM/High-Dose Rituximab Vs BEAM/Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) and Autologous Stem Cell Transplantation (ASCT) for Relapsed CD20+ Follicular and Diffuse Large B-Cell Lymphoma: Survival Outcomes and Risk of Secondary Malignancies

2011; Elsevier BV; Volume: 118; Issue: 21 Linguagem: Inglês

10.1182/blood.v118.21.2005.2005

1528-0020

Lisa Zipp, Rima M. Saliba, Rosamar Valverde, Grace‐Julia Okoroji, Martin Körbling, Barry I. Samuels, Lynne V. Abruzzo, Amin M. Alousi, Börje S. Andersson, Chitra Hosing, Bill Erwin, Paolo Anderlini, Uday Popat, Partow Kebriaei, Homer A. Macapinlac, Richard E. Champlin, Issa F. Khouri,

Chronic Lymphocytic Leukemia Research

Abstract Abstract 2005 Background: The addition of high-dose rituximab (hR) has been shown to improve results for pts with relapsed CD20+ diffuse large b-cell (DLBCL) and follicular (FL) lymphoma who undergo high-dose chemotherapy (HDC) with BEAM (hR-BEAM) followed by ASCT (Khouri, J. Clin.Oncol, 2005). More recently, we and others reported upon the safety of incorporating the radio-labeled antibody Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) to the BEAM conditioning (Z-BEAM). Herein, we compare the long-term outcomes, by histology, in 147 pts treated with these 2 regimens. Methods and Patients: Pts were treated on 2 consecutive trials. Both groups received R during stem cell collection with R administered at 375 mg/m2 on the day before initiating chemotherapy for stem cell mobilization, and again at 1000 mg/m2, 7 days later. Pts with hR-BEAM (n =111) received additional R at 1000 mg/m2 on days +1 and +8 after ASCT, as previously described. The Z-BEAM pts (n=36) received Zevalin® given at the fixed dose of 0.4 mCi/Kg on day –14 followed by HDC (days –7 to –1). There was no statistically significant difference in age, gender distribution, number of prior chemotherapies, stage, disease status (CR/PR), LDH and IPI at the time of transplant between the 2 groups. Serum b2- microglobulin level, was higher in the DLBCL pts who received R-BEAM than the Z-BEAM [median 2.3 vs 1.9, range 1.3–8 vs 1.2–6.5, respectively (p=.01). Both groups of pts were staged with CT, PET (whenever indicated) scans and marrow biopsies, every 3 months for the first year, every 6 months x5 years, then yearly thereafter. Results: A- DLBCL pts: Median follow-up for the DLBCL pts who received hR-BEAM (n=65) and Z-BEAM (n=25) was 97 months (range,17–122), and 56 months (range 34–78), respectively. OS at 5-year was 78% and 76%, respectively (p=0.7). PFS rates at 5-year were 78% for both. Within the R-BEAM group, PET status (expert review by H.M.) and LDH >nl at transplant were important prognostic factors for both OS {HR 4.9 and 5.9; p=0.001 for both) and PFS. IPI >1 was also determinant for PFS but not OS. We could not identify prognostic factors for OS in the Z-BEAM group; only advanced stage was found of importance for PFS. B-Follicular pts: Pts were considered for ASCT if they had no donors. Median follow-up for the FL pts who received hR-BEAM (n=46) and Z-BEAM (n=11) was 59 and 56 months, respectively. OS and PFS rates at 5-year were not statistically different [OS 77% vs 60%, (p=0.7), and PFS were 60% vs 45%, (p=0.4)}. The only determinant for both OS and PFS in the combined groups, was the number of prior chemotherapies of >2 prior transplant (HR 4.1 for OS, p=0.04; HR 2.5 for PFS, p=0.05). This confirms our earlier preliminary observation (ASH 2007). C. Secondary malignancies: All pts who received Z-BEAM, had routine cytogenetic analysis as well FISH for −7,-5 abnormalities performed on pre-transplant bone marrow samples. We found that the risk of secondary myelodysplasia or leukemia at 5-year to be 8% in both hR-BEAM and Z-BEAM. The risk of any other malignancies was also comparable (6% and 5%, respectively). Conclusions: Long follow-up analysis suggests that survival outcomes between Z-BEAM and hR-BEAM appear to be comparable, and that fixed dose Zevalin® of 0.4 mCi/kg can be added to BEAM without increasing the risk of secondary malignancies. DLBCL pts with PET+, or LDH> nl, or IPI>1 at transplant had inferior outcomes after hR-BEAM. Whether the addition of Zevalin® to the conditioning in this setting would improve outcomes is under investigation in a randomized trial at our center (protocol 2006–1018), using above prognostic factors for patients stratification. Disclosures: No relevant conflicts of interest to declare.