Phase 1 study of radiosensitization using bortezomib in patients with relapsed non-Hodgkin lymphoma receiving radioimmunotherapy with 131I-tositumomab.

Rebecca L Elstrom, Jia Ruan, Paul J Christos, Peter Martin, Daniel Lebovic, Joseph Osborne, Stanley Goldsmith, June Greenberg, Richard R Furman, Anca Avram, Ryan Putman, Erica Chapman, Madhu Mazumdar, Kent Griffith, Morton Coleman, John P Leonard, Mark S Kaminski

Journal: Leukemia & lymphoma 2016;56(2):342-6

PMID: 24730538

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Abstract

Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin lymphomas (NHLs), but response durations are usually limited, especially in aggressive NHL. We hypothesized that administration of bortezomib as a radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This phase 1 dose-escalation study evaluated escalating doses of bortezomib combined with 131I-tositumomab in patients with relapsed/refractory NHL. Twenty-five patients were treated. Treatment was well tolerated, with primarily hematologic toxicity. The maximum tolerated dose (MTD) was determined to be 0.9 mg/m2 bortezomib, in combination with a standard dose of 75 cGy 131I-tositumomab. Sixteen patients responded (64%), including 44% complete responses (CRs), with 82% CR in patients with follicular lymphoma (FL). At a median follow-up of 7 months, median progression-free survival was 7 months, and seven of 11 patients with FL remained in remission at a median of 22 months. In conclusion, bortezomib can be safely administered in combination with 131I-tositumomab with promising response rates.

Address: Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College , New York, NY , USA.

DOI: 10.3109/10428194.2014.914195

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MeSH Terms: Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Bortezomib, Chills, Combined Modality Therapy, Disease-Free Survival, Fatigue, Female, Humans, Iodine Radioisotopes, Lymphoma, Non-Hodgkin, Male, Middle Aged, Neoplasm Recurrence, Local, Neutropenia, Radiation-Sensitizing Agents, Radioimmunotherapy, Remission Induction, Thrombocytopenia, Treatment Outcome