Abstract
Abstract 662
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.
No relevant conflicts of interest to declare.
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