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

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.

• Authors: 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 (Leuk Lymphoma) Vol. 56 Issue 2 Pg. 342-6 (Feb 2015) ISSN: 1029-2403 [Electronic] United States
• PMID: 24730538 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Iodine Radioisotopes
• Radiation-Sensitizing Agents
• Bortezomib
• tositumomab I-131

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Bortezomib (adverse effects, therapeutic use)
• Chills (etiology)
• Combined Modality Therapy
• Disease-Free Survival
• Fatigue (etiology)
• Female
• Humans
• Iodine Radioisotopes (adverse effects, therapeutic use)
• Lymphoma, Non-Hodgkin (therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neutropenia (etiology)
• Radiation-Sensitizing Agents (adverse effects, therapeutic use)
• Radioimmunotherapy (adverse effects, methods)
• Remission Induction
• Thrombocytopenia (etiology)
• Treatment Outcome