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
Authors: Zipp Lisa , Saliba Rima M , Valverde Rosamar , Okoroji Grace-Julia , Korbling Martin , Samuels Barry I , Abruzzo Lynne V. , Alousi Amin M , Andersson Borje S , Hosing Chitra M , Erwin Bill , Anderlini Paolo , Popat Uday R , Kebriaei Partow , Macapinlac Homer A , Champlin Richard , Khouri Issa F. 
Published: October 2019

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.