Zevalin®/BEAM/Rituximab vs BEAM/Rituximab and Autologous Stem Cell Transplantation (ASCT) for Relapsed Chemosensitive Diffuse Large B-Cell Lymphoma (DLBCL): Impact of the IPI and PET Status.
Authors: Alousi Amin M. , Hosing Chitra , Saliba Rima M. , Valverde Rosamar B. , Maadani Farzaneh , Korbling Martin , Okoroji Grace J. , Fayad Luis E. , Stachowiak Anne M. , Erwin William D. , Anderlini Paolo , de Lima Marcos J. , Giralt Sergio A. , Popat Uday R. , Kebriaei Partow , Ueno Naoto T. , McLaughlin Peter W. , Pro Barbara , Wang Michael , Rodriguez Alma , Hagemeister Fredrick B. , Macapinlac Homer A. , Podoloff Donald A. , Champlin Richard E. , Khouri Issa F. 
Published: October 2019

Background: The addition of rituximab (R) has improved results for pts with relapsed DLBCL who undergo high-dose chemotherapy followed by ASCT (Khouri, JCO, 2005). Recently, the incorporation of radio-labeled antibodies such as Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) to conditioning regimens has been evaluated. Herein, we compare the outcome in pts treated with these 2 regimens.

Methods: Pts with relapsed chemosensitive DLBCL were treated on 2 consecutive trials. Between 1999 and 2003, 53 pts were enrolled on a protocol with BEAM combined with R at 1000 mg/m2 and on days +1 and +8 after ASCT (R-BEAM). Between 2004 and 2006, 25 pts were entered onto a trial of Zevalin given at the fixed dose of 0.4 mCi/Kg on day -14 followed by BEAM (days −7 to −1) with R on days +1 and +8 after ASCT (Z-BEAM). Both groups received R during stem cell collection at a dose of 375 mg/m2 the day before chemotherapy for stem cell mobilization and at 1000 mg/m2 7 days later. There was no statistical difference in age, sex distribution, # of prior therapies between the 2 groups. LDH, PET and remission status at transplant were comparable. However, serum b2- microglobulin level was higher in R-BEAM pts [median 2.2 vs 1.9, (p=.02)] and they were also more likely to have an IPI ≥ 1: 39% vs 8% (p=0.005).

Results: Median follow-up: 18 mos (range, 6–35) in Z-BEAM and 52 mos (range, 21–74) for R-BEAM. Both groups were staged with CT, PET scan and marrow biopsies, every 3 mos for a year, and then every 6 mos. OS and DFS @ 2 yrs were 92% (95% CI, 72–98) and 84% (95% CI, 62–93) for Z-BEAM vs. 83% (95%CI, 70–91) and 72% (95% CI, 57–82) for R-BEAM (P = 0.5 for both OS/DFS). Within the R-BEAM group, PET status and IPI at transplant were important prognostic factors for OS {91% vs 50% for PET (−) and (+), P = 0.004; 94% vs 67% for IPI 0 vs. ≥1, P = 0.02} and DFS. DFS of pts with IPI 0 were 86% vs 81% for Z-BEAM and R-BEAM, respectively (P = 0.9). A comparison for high IPI pts could not be done due to the small number of such pts in the Z-BEAM group. DFS for pts who were PET (+) were 75% vs 44% within the Z-BEAM and R-BEAM groups, respectively: a difference that did not reach significance due to the small number of pts (4 vs 10). Treatment-related mortality was comparable with only one early death within the Z-BEAM group due to sepsis. Results suggest a faster WBC recovery with Zevalin {ANC > 500, day +9 vs. day +11 (p<0.001)}. However, results may be confounded by the use of different cytokines. Platelet engraftment was similar in both groups.

Conclusions: Fixed dose Zevalin of 0.4 mCi/kg can be added to BEAM without increasing toxicity. Z-BEAM and R-BEAM have comparable results in relapsed chemosensitive DLBCL pts with IPI 0 and PET (−) at transplant. Pts with IPI ≥ 1 and PET (+) have suboptimal results with R-BEAM. Randomized trials are needed to address whether the addition of Zevalin for these pts may improve their outcome.