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

Research output: Contribution to journalArticlepeer-review

110 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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