High-dose radioimmunotherapy with yttrium 90 (90Y) ibritumomab tiuxetan with high-dose etoposide (VP-16) and cyclophosphamide (CY) followed by autologous hematopoietic cell transplant (AHCT) for poor-risk or relapsed B-cell non-Hodgkin's lymphoma (NHL): Update of a phase I/II trial

Abstract

6504 Background: A phase I/II trial investigated whether high-dose ibritumomab tiuxetan (Zevalin [Z]) can be safely combined with high-dose VP-16 40–60 mg/kg and CY 100 mg/kg as a conditioning regimen for AHCT. Methods: Patients undergo dosimetry study (day -21) with 5 mCi 111In-ibritumomab tiuxetan following 250 mg/m2of rituximab to confirm favorable biodistribution followed by (day -14) 40–100 mCi to deliver a target dose of 1000 cGy to highest normal organ and then VP-16 (day -4) and CY (day -2). Bone marrow biopsy is done on day-7 to estimate radiation dose and stem cells are reinfused when the radiation dose to reinfused cells is estimated to be < 5 cGy. Results: Between 5/00 and 11/03, 31 patients (17 M: 14 F), median age 51 (range, 25–59.6) with follicular (n=9), diffuse large B-cell (n=17) and mantle cell (n=5) were treated. Disease status at AHCT: 1stCR/PR=7, REL/IF = 14 and ≥2ndCR=10. Median number of prior chemo regimens was 2 (range, 1–6). All but two had received rituximab either alone (8), or in combination with chemotherapy (21). Six received VP-16 40 mg/kg while 25 received 60 mg/kg. The median dose was 70.8 mCi (range 36.6–105). The treatment was well tolerated with no transplant-related death. Mucositis, neutropenic fever and skin rash were the most common acute toxicities. All but one patient engrafted; median time to reach ANC > 500/μl and platelet > 20,000/μl was 10 days (range 8–17) and 19 days (range 12–123), respectively. There were 4 relapses at 3, 4, 12 and 24 months post AHCT. At a median follow-up of 21 months (range 1.4–43), the 2-year estimated OS and DFS is 93%(95% CI, 86–96%), and 80% (95% CI, 64–96%), respectively. Conclusion: High-dose can be safely combined with high-dose VP-16 and CY without increase in transplant-related toxicity or delay engraftment. This novel preparative regimen is well tolerated and is effective in patients with refractory B-cell NHL. Further studies and longer follow-up are required to determine the curative potential of this regimen Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Inc. Biogen Idec, Inc. Biogen Idec, Inc. Biogen Idec, Inc.