A Phase II Study of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Treatment of Patients with Relapsed and Refractory Mantle Cell Lymphoma (MCL).

Background: The management of MCL is a significant therapeutic challenge, especially in patients with relapsed or refractory disease, who are generally refractory to salvage chemotherapy. Although recent studies have shown the clinical utility of radioimmunotherapy (RIT) in relapsed and transformed indolent B-cell lymphoma, the clinical efficacy of this treatment modality in patients with MCL is unknown. We report the results of an ongoing phase II clinical trial of yttrium 90 ibritumomab tiuxetan (Zevalin®) in patients with relapsed and refractory MCL.

Patients and Methods: Patients with relapsed or refractory MCL with measurable disease, age >18 years, and performance status <3 were eligible. Patients were required to have adequate function of the bone marrow (ANC >1,500/mm3, platelets >100,000/mm3), liver, and kidneys. Patients were excluded if they had prior stem cell transplantation, RIT, CNS lymphoma, HIV infection, pleural effusion, HAMA reactivity, or circulating lymphoma cell count >5000/mm3. Patients with pretreatment platelet counts >150,000/mm3 received a dose of Zevalin at 0.4 mCi 90Y/kg (maximum dose 32 mCi), whereas those with platelet counts <150,000/mm3 received 0.3 mCi 90Y/kg.

Results: Fifteen patients were enrolled and all qualified for evaluation of treatment response and toxicity. The median age was 64 years (range 51–77), and 13 patients were male. All patients had an ECOG performance status of 0 or 1 and had been previously treated with rituximab with or without other chemotherapy. The median number of prior regimens was 3 (range 1–6). Six of the patients did not respond to their last regimen, while another 6 achieved only a partial response to the last regimen. Ten patients were previously treated with Hyper-CVAD alternating with MTX/Ara-C. Zevalin treatment was generally well tolerated, with the most common toxicities being hematologic. The median times to nadir for platelet and neutrophil counts were 41 days (range 26–63) and 48 days (26–65), respectively. Median durations of platelet (<50,000/mm3) and neutrophil (<1,000/mm3) toxicities were 15 days (range 0–68+) and 0 days (range 0–62), respectively. Three patients required platelet transfusions (range 1–3), and 5 experienced neutrophil toxicity (<1,000/mm3), for which G-CSF was administered until neutrophil recovery. One patient was admitted to the hospital with neutropenic fever and documented stenotrophomonas maltophilia sepsis, which was successfully controlled with IV antibiotics. Objective responses were observed in 5 patients (33%), including 3 CR and 2 CRu. Two additional patients had a minor response, and 1 patient had stable disease. Among the 4 patients who received a Zevalin dose of 0.3 mCi 90Y/kg, 1 achieved a CRu while the 3 others had progressive disease. Response was observed in all IPI score groups (0–3). Response rate was higher in patients who had had 1 or 2 prior regimens than in patients with 3 or more prior regimens (67% vs 11%, p<0.001). Median progression free survival for entire group was 4.9 months and median response duration of CR/CRu patients was 5.7 months. At the moment, three patients are free of progression at 123, 200 and 380 days.

Conclusion: The observed responses to Zevalin in heavily pretreated patients with MCL are promising and warrant further investigation of its activity after first or second relapse, and in conjunction with front-line therapy.