Evidence Mounts for the Efficacy of Radioimmunotherapy for B-Cell Lymphomas

Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA.
Journal of Clinical Oncology (Impact Factor: 17.88). 11/2008; 26(32):5147-50. DOI: 10.1200/JCO.2008.18.5447
Source: PubMed
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    ABSTRACT: Metastatic disease after successful treatment of the primary tumor continues to be a therapeutic challenge. Enhancement of therapeutic effects by the administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy (RIT) may provide a means of preventing or delaying the development of metastatic disease. In the present study, Brown Norway rats with syngeneic grafted colon carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg lutetium-177 ((177)Lu)-DOTA-BR96. After 2 weeks, half of the animals were given 15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and toxicity were monitored 100 days after the treatment with unlabeled BR96. The treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19 of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The additional treatment did not affect the number of animals with metastatic disease or the time to clinical symptoms of metastases. RIT resulted in reversible myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity, making it possible to repeat the consolidation therapy.
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    ABSTRACT: Abstract A standard salvage therapy of relapsed/refractory aggressive non-Hodgkin lymphoma (NHL) comprises autologous stem cell transplantation (ASCT) after chemotherapy conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM) regimen. However, the achievement of long-term disease-free survival remains challenging. We have introduced concomitant (131)I-rituximab radioimmunotherapy (RIT) in an attempt to effect the elimination of lymphoma cells. Our phase II physician-sponsored study of 16 consecutive patients with relapsed, refractory, aggressive B-cell NHL reports a median 44 month follow-up after (131)I-rituximab-BEAM conditioning therapy and ASCT. Prospective personalized dosimetry performed in each patient limited the whole body radiation absorbed dose to 0.75 Gy. RIT (131)I-rituximab was administered on an outpatient basis on day -15 before ASCT. The BEAM conditioning regimen was commenced on day -6. Evaluable engraftment data are available for 15 patients who had 16 ASCTs. Engraftment was achieved in all patients, 15 out of 16 ASCTs achieved a complete response, and 1 out of 15 ASCTs achieved a partial response. Twelve out of sixteen patients remained alive and disease free at a median of 44 months (range 4-108 months) post-ASCT. This study suggests that the addition of (131)I-rituximab RIT to BEAM conditioning, before ASCT, for relapsed or primary refractory B-cell NHL improves disease eradication, compared with BEAM conditioning alone, without significant additional toxicity. In particular, there is an impression of improved disease control in the subset of patients with transformed follicular and mantle cell lymphomas.
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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; DOI:10.3324/haematol.2014.112110 · 5.87 Impact Factor


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