SAN DIEGO, CA—Clinical findings presented at the American Society of Hematology’s 53rd Annual Meeting and Exposition demonstrated fractionated radioimmunotherapy (RIT) using 90Y-ibritumomab tiuxetan to be effective as initial chemotherapy of advanced-stage follicular lymphoma (FL) in patients with high tumor burden. Dr. Timothy M. Illidge, MD, PhD, of the School of Cancer and Enabling Sciences, University of Manchester, Manchester, UK and colleagues conducted an international, multicenter Phase 2 trial to evaluate the efficacy and toxicity of fractionated 90Y-ibritumomab tiuxetan RIT as a first-line treatment of relapsed FL.
Patients enrolled included those with untreated FL (Grade 1, 2, or 3a) and at least one criterion of high tumor burden: one lymphoma lesion >7cm or three separate nodes of ≥3cm; symptomatic splenic enlargement; raised serum concentrations of either lactate dehydrogenase or ß2-microglobulin; compressive syndrome; or the presence of B symptoms. 90Y-ibritumomab tiuxetan 11.1MBq/kg was administered as two doses given 8–12 weeks apart. Patients with >20% bone marrow (BM) involvement received fractionated RIT only if a repeat BM biopsy demonstrated a reduction to ≤20% involvement following four weekly infusions of rituximab 375mg/m2. The primary endpoint was the end of treatment response (EOR) of the intent-to-treat population according to International Workshop Criteria 1999. EOR was assessed 12 weeks after the last 90Y-ibritumomab tiuxetan infusion (21 weeks after start of treatment). Secondary objectives were safety and progression free survival (PFS).
A total of 72 patients were included in the study. Fifty-nine patients (78%) patients were Stage III/IV, 24 patients (31.6%) were classified as intermediate-risk Follicular Lymphoma International Prognostic Index (FLIPI) 2, and 35 patients (46.1%) were high risk FLIPI 3–5. Fourteen (18.4%) patients had >20% BM involvement and required rituximab pre-treatment. At least one 90Y-ibritumomab tiuxetan dose was administered to 72 patients, although two did not have any recorded response data. The second infusion was withheld if hematologic toxicity occurred following the first infusion or if the patient tested positive human anti-murine antibodies. Overall, 55 patients (76%) completed the full treatment schedule. Twelve out of 72 patients did not receive the second infusion due to hematological toxicity (16.7%), 4/72 declined due to HAMA (5.6%), and 1 patient developed manic psychosis (premorbid condition).
Study results showed the EOR to be 95.8% (67/70) with a complete response or unconfirmed complete response (CR/CRu) rate of 60% (41/72). Responses subsequently improved for six patients, resulting in an adjusted overall response rate (ORR) of 97.2% (68/70) (95% CI: 90–99.7) and CR/CRu of 65% (45/70) (95% CI: 51.9–75.4). For the 17 patients who only received the first 90Y-ibritumomab tiuxetan infusion, ORR and CR/CRu were 100% and 76.5%, respectively. PFS was 67% (median follow-up, 1.52 years): 20 patients have progressed and 12 have required additional treatment (eight chemotherapy, two radiotherapy, and two other).
Ten patients experienced a serious adverse event (AE); three were related to study treatment (one case of rigors associated with the first infusion of rituximab and two cases of neutropenic sepsis associated with the second RIT dose). Hematologic toxicities were the most common and included transient Grade 3–4 neutropenia (20.8%) and thrombocytopenia (20.8%) following the initial 90Y-ibritumomab tiuxetan dose. After the second 90Y-iritumomab tiuxetan dose, the rate of neutropenia and thrombocytopenia increased (36.4% and 56.4%, respectively). Anemia also occurred in 14% of patients.
Dr. Illidge states that, “fractionated RIT using 90Y-ibritumomab tiuxetan is an effective frontline treatment of advanced-stage FL in patients with high tumor burden requiring treatment and delivers high response rates.” The study investigators concluded that the treatment was well tolerated by patients with few infectious episodes and had a manageable toxicity profile. This is a convenient regimen for the patient and a feasible treatment option for patients who require treatment for follicular lymphoma, the researchers concluded.