Positron emission tomography-directed therapy for patients with limited-stage diffuse large B-cell lymphoma: Results of intergroup national clinical trials network study S1001

Daniel O. Persky, Hongli Li, Deborah M. Stephens, Steven I. Park, Nancy L. Bartlett, Lode J. Swinnen, Paul M. Barr, Jerome D. Winegarden, Louis S. Constine, Thomas J. Fitzgerald, John P. Leonard, Brad S. Kahl, Michael L. LeBlanc, Joo Y. Song, Richard I. Fisher, Lisa M. Rimsza, Sonali M. Smith, Thomas P. Miller, Jonathan W. Friedberg

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81 Scopus citations

Abstract

PURPOSE Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity. METHODS Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy. RESULTS Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes. CONCLUSION To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.

Original languageEnglish
Pages (from-to)3003-3011
Number of pages9
JournalJournal of Clinical Oncology
Volume38
Issue number26
DOIs
StatePublished - Sep 10 2020

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