A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by ⁹⁰Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma.
ABSTRACT A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkin's lymphoma (NHL) patients.
Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of (90)Y-ibritumomab tiuxetan ((90)Y-IT), 8-14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤ 25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS).
All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received (90)Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%.
This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with (90)Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.
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ABSTRACT: During the past decades, several radio-labelled monoclonal antibodies (mAb) have been tested in preclinical and clinical settings for radioimmunotherapy (RIT) of non-Hodgkin's Lymphomas (NHL). The only compounds that have been registered for RIT of relapsed/refractory NHL are 131 I-tositumomab (Bexxar ®) and 90 Y-ibritumomab-tiuxetan (Zevalin ®), both directed against CD20, indicating the favorable immunological characteristics of such antigen expressed by B-cell surface. The presence of a high-energy β -emitting radioactive source offers the unique chance to enhance the therapeutic effect of the antibody itself. Indeed, the proposed ―cross-fire effect‖ seems to overcome some of the mechanisms underlying resistance to mAb, allowing for killing neighboring cancer cells not expressing the CD20 antigen. The present chapter will summarize the clinical results of both Zevalin ® and Bexxar ® in the treatment of relapsed/refractory B-cell NHL. Efficacy in first line and consolidation therapy will be also discussed, as well as the inclusion of RIT in myeloablative chemo-regimens.01/2013: pages 103-123; , ISBN: 978-1-62257-533-6