Collection of Hematopoietic Stem Cells After Previous Exposure to Ittrium-90 Ibritumumab Tiuxetan (Zevalin) Is Feasible and Does Not Impair Autologous Stem Cell Transplantation Outcome in Follicular Lymphoma.
Authors: Derenzini Enrico , Pellegrini Cinzia , Maglie Roberto , Stefoni Vittorio , Broccoli Alessandro , Gandolfi Letizia , Casadei Beatrice , Quirini Federica , Argnani Lisa , Fanti Stefano , Motta Maria Rosa , Baccarani Michele , Zinzani Pier Luigi 
Published: October 2019

Abstract
Abstract 3019

Background:
Radioimmunotherapy (RIT) is an effective and manageable treatment option for those patients (pts) affected by follicular B-cell lymphoma (FL) who experience disease relapse. The results of RIT in the setting of first line consolidation are also very promising in terms of progression free and overall survival. On the other hand autologous stem cell transplantation (ASCT) is a suitable treatment option for relapsed FL patients. Although major concerns about the widespread use of RIT early in the disease course are the long term hematologic toxicity and the theoretical possible irreparable damage to bone marrow function with impairment of peripheral stem cell harvest, very few data are available about mobilization rates after Zevalin exposure.

Methods:
The aim of this monocentric study was to analyze the impact of prior Zevalin administration on peripheral blood stem cells (PBSC) mobilization and on the outcome of subsequent ASCT. Moreover the impact of different prior treatment regimens [Cyclophosphamide, Doxorubicin, Vincristine, Prednisone plus Rituximab (R-CHOP) or CHOP-like regimens vs Fludarabine, Mitoxantrone plus Rituximab (FM-R) vs Zevalin] and number of previous lines of therapy given earlier in the disease course, was prospectively evaluated in all FL patients (n=100) who underwent stem cell mobilization from January 2005 to March 2012.

Results:
At the time of mobilization, 68 pts had received R-CHOP or CHOP-like regimens, 20 pts FM-R, 12 pts RIT with Zevalin earlier in the disease course. Characteristics of pts such as age, weight and number of prior therapies, were well balanced in the 3 groups. Sixty one pts had received one prior therapy, 31 pts 2 therapies, 8 pts ≥ 3 lines of therapy. All pts received chemotherapy plus granulocyte colony stimulating factor (G-CSF) 5 μg/kg (n=94) or G-CSF alone (10 μg/kg) (n=6) as mobilization regimen. Mean CD34+ cells yield was 8.9 × 106/kg in the CHOP group, vs 5.8 × 106 CD34 + cells/kg in the FM-R group, vs 2.7 × 106 CD34 + cells/kg in the Zevalin group (p=0.05 CHOP vs FM-R; p<0.001 CHOP vs Zevalin; p<0.01 FM-R vs Zevalin; t test). The collection yield of 2.0 × 106 CD34 + cells/kg was reached in 98% (n=67) of pts in the CHOP group, vs 80% (n=16) in the FM-R group, vs 42% (n=5) in the Zevalin group. The number of previous treatments did not significantly affect PBSC harvest (1 vs 2 lines: p=0.1; 1 vs 3 lines: p=0.1; 2 vs 3 lines: p=0.3). Regarding the engraftment no differences were noted between the 3 groups and the median time to neutrophils (> 1000/μL) and platelets recovery (>20000/μL) was 10 and 11 days in all groups respectively. Only one pt in the CHOP group and one in the FM-R group did not undergo ASCT because of insufficient CD34+ harvest. Considering the Zevalin group (n=12), median age was 51 years (range 36–66). Seven pts received Zevalin as first line consolidation, 5 patients at disease relapse. Median number of prior therapies was 2 (range 1–4). Ten pts received chemotherapy plus G-CSF as initial mobilization regimen, 2 pts received G-CSF alone. Median time from RIT to mobilization was 13 months (4–60 months). Five pts (42%) reached the collection yield of > 2.0 × 106 CD34 + cells/kg with the first mobilization attempt. Considering the remaining 7 pts who failed (CD34+ cells below 10/mL before apheresis, or cell harvest below 2.0 × 106 CD34 + cells/kg), a surgical procedure was attempted in 4 pts, G-CSF + Plerixafor (240 μg/kg) in 3 pts. Remarkably the second harvest allowed 5 additional pts (3 pts after surgery, 2 pts after G-CSF + Plerixafor) to undergo ASCT. Finally ASCT was succesfully performed in 9 pts (75%). Median number of reinfused CD34+ cells was 2.3 × 106 CD34 + cells/kg (0.4–4.2). Three pts did not undergo ASCT, one because of disease progression, 2 pts because of insufficient CD34+ harvest.

Conclusions:
The type of previous therapy may significantly influence the mobilization rate in FL pts. Although mobilization was significantly impaired in pts previously treated with Zevalin compared to other chemotherapy regimens, stem cell harvest after RIT was feasible and the vast majority of patients retained the possibility to undergo ASCT with a second stem cell harvest, with no significant impact on engraftment. The use of Plerixafor seems to be particularly promising for those patients previously exposed to RIT who failed the first mobilization.

Disclosures:
No relevant conflicts of interest to declare.