Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 166, Issue 3, Pages 382-389Publisher
WILEY
DOI: 10.1111/bjh.12906
Keywords
lymphoma; chemotherapeutic approaches; diffuse large B cell lymphoma; radioimmunotherapy; pharmacotherapeutics
Categories
Funding
- University of Rochester SPORE in lymphoma [CA 130805]
- National Cancer Institute, DHHS, PHS [CA32102, CA38926, CA11083, CA20319, CA35090, CA13612, CA46368, CA27057, CA35128, CA35119, CA46282, CA45450, CA12644, CA04919, CA073590]
- GlaxoSmithKline
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Radiolabelled antiCD-20 antibodies have demonstrated single agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). The S0433 clinical trial enrolled patients with newly diagnosed, advanced stage or bulky stage II, histologically confirmed DLBCL. Patients received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles of CHOP, then iodine-131 tositumomab radioimmunotherapy consolidation 30-60 d after completion of chemotherapy. The primary end-point was 2-year progression-free survival (PFS). Eighty-four eligible patients were enrolled, and 56 patients completed the entire course of protocol treatment. Of the 84 patients evaluable for treatment response, 72 [86%, 95% confidence interval (CI): 76-92%] achieved a partial response (n = 21) or a confirmed (n = 41) or unconfirmed (n = 10) complete response to therapy. With a median follow-up of 3.9 years, the 2-year PFS estimate is 69% and the 2-year overall survival estimate is 77%. Rituximab levels at time of radioimmunotherapy did not correlate with toxicity or outcome. Twenty percent of patients had double hit features (MYC+; BCL2+) by immunohistochemistry, and had inferior outcome. These current results suggest that the incorporation of novel agents earlier in therapy may ultimately have greater impact in DLBCL, as early progressions, deaths and declining performance status during CHOP chemotherapy limited the number of patients who ultimately could benefit from radioimmunotherapy consolidation.
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