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. 2015 Aug 10;33(23):2516-22.
doi: 10.1200/JCO.2014.59.7534. Epub 2015 Jun 29.

Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

Carla Casulo  1 , Michelle Byrtek  1 , Keith L Dawson  1 , Xiaolei Zhou  1 , Charles M Farber  1 , Christopher R Flowers  1 , John D Hainsworth  1 , Matthew J Maurer  1 , James R Cerhan  1 , Brian K Link  1 , Andrew D Zelenetz  1 , Jonathan W Friedberg  2
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Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

Carla Casulo et al. J Clin Oncol. .

Erratum in

  • J Clin Oncol. 2016 Apr 20;34(12):1430
  • ERRATUM.
    [No authors listed] [No authors listed] J Clin Oncol. 2016 Apr 20;34(12):1430. doi: 10.1200/JCO.2016.67.4879. J Clin Oncol. 2016. PMID: 31265520 Free PMC article.

Abstract

Purpose: Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death.

Patients and methods: In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility.

Results: Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index-adjusted hazard ratio, 19.8).

Conclusion: In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram for participant selection. One patient who experienced progression of disease (POD) before receiving rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was excluded. FL, follicular lymphoma; NLCS, National LymphoCare Study; R-CVP, rituximab with cyclophosphamide, vincristine, and prednisone; R-Flu, rituximab with fludarabine.
Fig 2.
Fig 2.
Estimated hazard of progression for the (A-C) National LymphoCare Study and (D) University of Iowa and Mayo Clinic Molecular Epidemiology Resource validation cohorts. (A) Rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP); (B) rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); (C) rituximab with fludarabine (R-Flu); (D) validation set (R-CHOP).
Fig 3.
Fig 3.
(A) Overall survival (OS) from a risk-defining event after diagnosis in patients who received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in the National LymphoCare Study group. Patients with early progression of disease (POD) had poor survival. Two-year OS was 68% (95% CI, 58.2% to 76.3%). Five-year OS was 50% (95% CI, 39.4% to 59.2%). OS in the reference group was 97% (95% CI, 94.6% to 98.1%) at 2 years and 90% (95% CI 86.2% to 92.4%) at 5 years. (B) Patients in the validation set who received R-CHOP with early POD also had inferior OS.
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Comment in

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