High rates of durable responses with anti-CD22 fractionated radioimmunotherapy: results of a multicenter, phase I/II study in non-Hodgkin's lymphoma.
ABSTRACT Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL).
A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined.
At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months.
Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.
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ABSTRACT: Targeted therapies represent a major breakthrough in the treatment of adult acute lymphoblastic leukaemia (ALL). Because lymphoblastic leukaemia cells express a variety of specific antigens, those ones can serve as targets for monoclonal antibodies (MoAbs). Anti-CD20 (rituximab), anti-CD19 (blinatumomab, SAR3419), anti-CD22 (epratuzumab, inotuzumab ozogamicin), and anti-CD52 (alemtuzumab) have therefore been developed. Possible strategies even include recruitment of CD3 cytotoxic T cells (blinatumomab) or adoptive T-cell therapy by gene transfer of CD19-chimeric antigen receptors (CD19-CARs). Recent data show that antibody-based therapy is a highly promising treatment approach. However, optimal treatment approach still needs to be defined.This article is protected by copyright. All rights reserved.European Journal Of Haematology 06/2014; · 2.41 Impact Factor
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ABSTRACT: A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabelled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated anti-CD22 90Y-epratuzumab tetraxetan with anti-CD20 veltuzumab in patients with aggressive lymphoma who had failed at least one prior standard treatment, but had not undergone stem cell transplant. Eighteen patients (median age 73 years, 3 median prior treatments) received 200 mg/m2 veltuzumab once-weekly for 4 weeks, with 90Y-epratuzumab tetraxetan at planned doses on weeks 3 and 4, and 111In-epratuzumab tetraxetan on week 2 for imaging and dosimetry. Veltuzumab effectively depleted B-cell blood levels prior to radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. 111In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For 90Y, transient myelosuppression was dose-limiting with 6 mCi/m2 (222 MBq/m2) x 2 the maximal tolerated dose. Of 17 assessable patients, 9 (53%) had objective responses by 2007 revised treatment response criteria, including 3 (18%) complete responses (two relapsing after 11 and 13 months, one continuing clinically disease-free at 19 months), and 6 (35%) partial responses (one relapsing after 14 months, 5 at 3 - 7 months). Responses occurred across different lymphoma histologies, 90Y dose levels, and prognostic risks of poor outcome, most importantly including 5/6 patients at the maximal tolerated dose (two achieving durable complete responses). In conclusion, this combination regimen was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.Haematologica 08/2014; · 5.94 Impact Factor
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ABSTRACT: Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies (including those fragments) or peptides. In a clinical field, two successful examples of this treatment protocol are currently extended by (90)Y-ibritumomab tiuxetan (Zevalin) and (131)I-tositumomab (Bexxar), both of which are anti-CD20 monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the treatment of non-Hodgkin lymphoma patients. In addition, some beneficial observations are obtained in preclinical studies targeting solid tumors. To date, in order to reduce the unnecessary exposure and to enhance the therapeutic efficacy, various biological, chemical, and treatment procedural improvements have been investigated in RIT. This review outlines the fundamentals of RIT and current knowledge of the preclinical/clinical trials for cancer treatment.TheScientificWorldJournal. 01/2014; 2014:492061.