Nonmyeloablative Allogeneic Stem Cell Transplantation with/ or without 90yttrium Ibritumomab Tiuxetan (90YIT) Is Curative for Relapsed Follicular Lymphoma: Median 9 Year Follow-up Results
Authors: Khouri Issa F , Saliba Rima M , Valverde Rosamar , Samuels Barry I , Korbling Martin , Alousi Amin M , Anderlini Paolo , Bashir Qaiser , De Lima Marcos , Hosing Chitra , Kebriaei Partow , Nieto Yago , Popat Uday R , Qazilbash Muzaffar , Neelapu Sattva , Fowler Nathan H. , Samaniego Felipe , Wang Luhua , Champlin Richard , Macapinlac Homer A 
Published: October 2019

Abstract
Abstract 662

Purpose:
Fludarabine, cyclophosphamide, and rituximab (FCR) has been found to be an effective nonmyeloablative allogeneic conditioning for relapsed/chemosensitive follicular lymphoma (Khouri et al, Blood 2008;111:5530). Innovative strategies were needed to treat patients with refractory disease. To achieve this goal, we added in a subsequent trial 90YIT to the conditioning (90YIT-FC). We now report updated results of the FCR trial (n=47 pts), and outcomes after 90YIT-FC (n=26 pts). Methods: FCR regimen: Fludarabine (30mg/m2) and cyclophosphamide(750mg/m2) were each given daily for 3 days (-5 to −3) before transplantation. Rituximab was given at a dose of 375 mg/m2 on day –13 and 1000 mg/m2 on days −6, +1, and +8, as previously described. 90YIT-FC: A diagnostic dose of 111In-ibritumomab was administered on day-14, followed by a fixed dose of 0.4 mCi/kg 90YIT on day −7. FC chemo was then administered at the same dose and schedule (days −5 to −3) as described above. Tacrolimus and methotrexate was used for GVHD prophylaxis. In addition, thymoglobulin of 1 mg/kg was given on days −2, −1 in pts receiving an unrelated or HLA-mismatched donor. Results: A. Transplant with FCR. Median age was 53 years (range, 33–68) years. Median prior treatments was 3 (range, 2–7). At transplant, 96% had chemosensitive disease (38% CR, 62% PR); 15% were PET+; and 53% had IPI = 0. Forty five pts (96%) had a transplant from a matched sibling donor, and 2 from unrelated ones. Since the last update (Blood 2008), one pt had recurrent disease (responded to donor lymphocytes + rituximab); three deaths occurred while pts were in CR: one because of pancreatic cancer (with strong family history), one of infection, and one of unknown causes. With a median follow-up time of 107 months (range, 72–142), the OS and PFS rates at 10-year were 78% (95%CI, 62–87) and 72% (95% CI, 56–83), respectively. Lymphoma-free OS and PFS rates were 82% and 76%, respectively. B. Transplant with90YIT-FC. Compared to the FCR group, more pts within this group had refractory disease (non-responding or progressing with chemo-immunotherapy) at transplant (38% vs 4%, respectively, p<0.001), were PET+ {44% vs 15%, respectively, p=0.01; (expert review by H.A.M)}, and more had a matched unrelated or mismatched transplant (43% vs 4%, respectively, p <0.001). Other characteristics such as age, number of prior chemotherapy regimens, time from diagnosis to transplant, were not significantly different between the two groups. With a median follow-up of 23 months (range, 7–70), the 2-year OS and PFS rates were 88% and 85%, respectively, not statistically different from the 2-year OS and PFS of the FCR group (83% and 85%, respectively) (p=0.9) (Figure). The 2-year PFS rates for pts with refractory and sensitive disease were 80% and 87%, respectively (p=0.7). Findings after the 111In-ibritumomab scans (40% were positive) did not impact outcomes. The incidence of acute II-IV GVHD was 13% in FCR- and 23% in the 90YIT-FC group (p=0.2); the rates of acute III-IV GVHD were 2% and 8%, respectively; p= 0.3. We noticed an unexpected trend for a lower incidence of chronic extensive GVHD in the 90YIT-FC group (24% vs 40%, respectively, p=0.3), despite the higher proportion of unrelated transplants in that group. Conclusions: Nonmyeloablative allogeneic transplant can induce complete responses lasting over a decade in the majority of patients with relapsed follicular lymphoma. The addition 90YIT to the regimen appears to be particularly effective in relapsed refractory patients.

Disclosures:
No relevant conflicts of interest to declare.