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Fractionated 90Y-Ibritumomab Tiuxetan Radioimmunotherapy Produces High Response Rate in Initial Therapy for Follicular Lymphoma

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Key Points

  • Fractionated radioimmunotherapy with 90Y-ibritumomab tiuxetan produced response in 95.8% of patients, including complete response or unconfirmed complete response in 69.4%.
  • Hematologic toxicities were manageable and low rates of grade 3 or 4 infective complications and other nonhematologic adverse events were observed.

In a phase II trial reported in the Journal of Clinical Oncology, Illidge et al evaluated radioimmunotherapy with fractionated 90Y-ibritumomab tiuxetan (Zevalin) as initial treatment in patients with mostly advanced follicular lymphoma. The treatment was well tolerated, with manageable hematologic toxicity, and was associated with a high response rate.

Study Details

In this international trial, 74 patients requiring therapy according to Groupe d’Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria received two doses of 90Y-ibritumomab tiuxetan (11.1 MBq/kg) given 8 to 12 weeks apart. Patients with > 20% lymphoma infiltration of bone marrow received a weekly infusion of rituximab (Rituxan) at 375 mg/m2 for 4 consecutive weeks and then received fractionated radioimmunotherapy if repeat biopsy showed reduction in lymphoma to < 20% involvement. Patients had a median age of 61 years (range, 28–80 years), 78% had stage III or IV disease, and 32% and 44% had Follicular Lymphoma International Prognostic Index (FLIPI) intermediate and high risk.  

Responses

Initial response occurred in 68 (94.4%) of 72 evaluable patients, with complete response or unconfirmed complete response occurring in 42 (58.3%). Improvements in response subsequently occurred in nine patients, yielding an overall response rate of 95.8%, with complete response or unconfirmed complete response in 50 patients (69.4%). Median progression-free survival was 40.2 months.

At a median follow-up of 3.1 years, estimated 3-year progression-free survival was 58%, treatment-free survival was 66%, and overall survival was 95%. A total of 24 patients received additional treatment after progression, including chemotherapy in 21 and radiotherapy in 3.

Three-year progression-free survival was 66% in patients who initially achieved complete response or unconfirmed compete response and 54% in those achieving partial response. For patients achieving complete response, 3-year progression-free survival was 85% and median progression-free survival was not reached. Three-year progression-free survival was 49% vs 60% in patients with > 20% vs < 20% bone marrow involvement at baseline (P = .19), 50% vs 65% in those with tumors ≥ 50 mm vs < 50 mm (P = .47), and 65%, 76%, and 43% in those with low, intermediate, and high FLIPI risk (P = .051 for trend).

Toxicities

Among grade 3 or 4 hematologic toxicities, thrombocytopenia occurred in 21% of patients after one 90Y-ibritumomab tiuxetan infusion and 56% after two, thrombocytopenia occurred in 22% after two doses, and neutropenia occurred in 21% after one dose and 36% after two; grade 3 anemia occurred in 5.5% after two doses. Human antimouse antibody positivity was found in 9% of patients, with two patients having symptomatic skin rash.

The most common nonhematologic adverse events of grade 1 or 2 were lethargy/asthenia (42%), nausea (21%), musculoskeletal pain (15%), and dermatologic events (15%). Six grade 3 events were observed (8%), consisting of infective episodes in two patients (2.8%; both neutropenic sepsis), adverse reactions to rituximab in two, and lethargy and rash in one each. An additional 11% of patients had grade 1 or 2 infective complications.

Two cases of myelodysplastic syndrome were considered treatment-related. Six secondary malignancies were observed, consisting of acute myeloid leukemia, metastatic breast cancer, and incidental breast, basal cell skin, endometrial, and sigmoid carcinomas. Five patients died, two from progressive disease, one from metastatic breast cancer, one from acute myeloid leukemia, and one after allogeneic bone marrow transplantation for myelodysplastic syndrome.

The investigators concluded, “Fractionated [radioimmunotherapy] using [90Y-ibritumomab tiuxetan] is an effective initial treatment for advanced-stage [follicular lymphoma] in patients with higher tumor burden requiring treatment.”

Tim M. Illidge, BSc, PhD, MBBS, DRCOG, MRCP, FRCR, FRCPath, of the University of Manchester, United Kingdom, is the corresponding author for the Journal of Clinical Oncology article.

The study was funded by Bayer Schering Pharma. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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