Abstract

Allogeneic hematopoietic cell transplantation (HCT) using reduced intensity conditioning (RIC) regimens offers a potential curative therapy to patients with advanced indolent NHL. RIC HCT induces potent graft-versus-lymphoma effects, with best results in patients with low tumor burden at time of HCT. Combined use of radioimmunotherapy (RIT) with RIC may increase anti-lymphoma activity of RIC. A multicenter phase II study of allogeneic HCT combining RIT using yttrium-90-ibritumomab tiuxetan (Y90-CD20, Zevalin®) with 0.4 mCi (15 MBq)/kg on day -14 combined with RIC using fludarabine (30 mg/m2 day -4 to -2) and 2 Gy TBI (day 0) followed by allogeneic HCT from matched related or unrelated donors was initiated. Postgrafting immunosuppression consists of cyclosporine and mycophenolate mofetil. Targeted enrolment is 40 patients with dosimetry on day -21 in the first five patients. Primary objective of this study was the evaluation of treatment related mortality and engraftment after RIT-RIC HCT. Secondary objectives were disease response, relapse rate, disease free and overall survival, GVHD and immune reconstitution.

To date, 36 patients are evaluable. Diagnoses were follicular lymphoma (n=15), mantle cell lymphoma (n=8), chronic lymphocytic leukemia (n=11), marginal zone lymphoma (n=1) and immunocytoma (n=1). Median age was 56 (range, 34–68) years. PBSC grafts were either from matched related (n=11) or matched unrelated donors (n=25). All patients were “high risk” with refractory disease or relapse after preceding autologous HCT. Disease stage at time of HCT was CR=7, PR=24, SD=5. No additional toxicity due to RIT in comparison to our previous experience with the same RIC was observed. Engraftment was rapid and sustained with no graft rejections. Median time to >500 granulocytes/μL was 14 (range, 0–69) days, and to >20000 platelets/μL 8 (range, 0–69) days. In 14 patients platelets never dropped below 20000/μL and in 8 patients granulocytes never below 500/μL, illustrating the non-myeloablative intensity of the conditioning regimen. TRM in the first 100 days was 8% (n=3) and overall 25% (n=9). Incidence of grade II-IV GVHD was 44% (II=4, III=10, IV=2). To date, extensive chronic GVHD occurred in 6 patients. Deaths occurred due to infections=5, GVHD=2, relapse=2 and multi organ failure=2. 25/36 (69%) of all patients are alive with a median follow up of 453 (range, 39–713) days, resulting in a Kaplan-Meier estimate 1 year survival of 67%. Disease status of patients alive is CR=18 and PR=7.

In conclusion, a combination of RIT with RIC is feasible with no additional toxicity due to RIT and with stable engraftment in all patients. Disease response and treatment related mortality seems promising even in this elderly and heavily pretreated cohort but requires further follow-up.

Disclosures: Bethge:Bayer Healthcare: Honoraria, Research Funding. Off Label Use: use of yttrium-90-ibritumomab tiuxetan for mantle cell lymphoma, CLL, marginal zone lymphoma and in the context of reduced intensity conditioning.

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