Yttrium-90 Ibritumomab Tiuxetan Among Previously Untreated Patients with Low-Grade Follicular Lymphoma and Marginal Zone Lymphoma

Clinical trials of yttrium-90 ibritumomab tiuxetan [(90)Y-IT] have demonstrated a rate of high efficacy for this radio-immuno conjugate targeted to CD20 in the first-line, standalone treatment of follicular lymphoma (FL) and marginal zone lymphoma (MZL). The Food and Drug Administration (FDA) has approved (90)Y-IT for the treatment of relapsed or refractory, low-grade (LG) or follicular B-cell non-Hodgkin lymphoma (NHL) and of previously untreated patients with follicular NHL who achieved a partial or complete response to first-line chemotherapy. 

To assess long-term survival and toxicities after treatment with (90)Y-IT, researchers retrospectively conducted long-term follow-up of previously untreated patients with FL or MZL who received a standard dose of this radio-immuno conjugate as first-line treatment at a Mayo Clinic Cancer Center between 2000 and October 2019 (Clin Lymphoma Myeloma Leukemia. 2022; doi:10.1016/j.clml.2022.04.004). 

“FL and MZL are highly sensitive to radiation therapy….CD20 is a cell surface B-cell marker expressed in more than 95% of B-cell NHL and is a valid target for therapeutic development in B-cell malignancies,” wrote Muhamad Moustafa, MD, Mayo Clinic, Jacksonville, FL, and colleagues.

Their study group included 51 patients with previously untreated lymphoma; 41 had LG-FL, and 10 had MZL. Their median follow-up was 5.3 years (95% confidence interval [CI], 4.2 yr to 6.2 yr). Treatment resulted in a 100% overall response rate and a complete response rate of 94%. A continuously complete response was noted in 59% of patients with >2 years of follow-up (median follow-up, 6.1 yr), and a long-term (>7-year) complete response occurred in one-quarter of the patients studied. 

The median progression-free survival (mPFS) was not reached (95% CI, 4.9 yr to not reached) by the entire cohort. Bulky disease was associated with a shorter mPFS than non-bulky disease. For patients with bulky disease, mPFS was 3.5 years (95% CI, 0.8 yr to 4.9 yr), and for those with non-bulky disease, mPFS was not reached (95% CI, 5.8 yr to not reached). 

“The other significant finding is that high therapeutic efficacy of (90)Y-IT in the cohort is achieved with highly acceptable and manageable safety profile,” wrote Dr Mustafa and colleagues. More specifically, no patients experienced myelodysplasia or acute myeloid leukemia related to treatment, and the incidence of grade 3 or higher adverse events was 47% for thrombocytopenia, 37% for neutropenia, and 4% for anemia. 

“Grade 3/4 hematologic toxicities seen after (90)Y-IT treatment recover in most patients (96%) without requiring any transfusion or growth factor support,” Dr Mustafa and team continued, adding, “Hematologic recovery is fast with blood counts returning to the baseline in about 6 to 8 weeks. As such, the patients are not subjected to recurrent hematologic toxicities.”

“Long real-life follow-up showed that single-agent (90)Y-IT is highly efficacious with durable long-term survival in previously untreated LG-FL and MZL without significant risk for secondary malignancy,” Dr Moustafa and colleagues concluded, adding, “Moreover, (90)Y-IT treatment schedule is patient-friendly and not taxing on the patient…. The treatment requires only 1 week consisting of 3 intravenous infusions.”