Complete response to induction therapy in patients with Myc-positive and double-hit non-Hodgkin lymphoma is associated with prolonged progression-free survival

Cancer. 2014 Jun 1;120(11):1677-85. doi: 10.1002/cncr.28642. Epub 2014 Feb 27.

Abstract

Background: Myc-positive B-cell non-Hodgkin lymphoma (NHL) with or without a B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) rearrangement is associated with inferior progression-free survival (PFS) and overall survival (OS). In this study, the authors reviewed the outcomes of patients with myc-positive and double-hit NHL at The Ohio State University.

Methods: All patients who had non-Burkitt, aggressive B-cell NHL from 2008 to 2011 were assessed for the t(14;18) translocation and for v-myc avian myelocytomatosis viral oncogene homolog (CMYC) rearrangements at diagnosis, and all myc-positive patients were included in the current analysis. Associations with clinical characteristics were described, and univariable and multivariable models were used to assess correlations between clinical variables and outcomes.

Results: Of 49 myc-positive patients, 29 patients also had BCL2 rearrangements (double-hit NHL). No patients underwent autologous stem cell transplantation in first remission. For all myc-positive patients, the median PFS was 16.6 months, and the median OS was 37.7 months. For patients who had double-hit NHL, the median PFS was 8 months, and the median OS was 12.5 months; whereas the median PFS and OS were not reached for myc-positive patients. A complete response (CR) after front-line therapy, the presence of t(14;18), International Prognostic Index (IPI) group, and age were associated with PFS; whereas only the achievement of a CR and age >60 years were associated with OS in the multivariable setting. The median PFS was 3.3 months, and the median and OS was 7.0 months for patients who did not attain a CR; and the medians were not reached for patients who achieved a CR (P < .00001).

Conclusions: The achievement of a CR with front-line therapy is associated with a prolonged PFS and OS in patients with myc-positive NHL, even after adjusting for type of initial therapy, histology, age, IPI, or the presence of a concurrent BCL2 translocation.

Keywords: B-cell lymphoma; C-myc genes; immunoglobulin heavy chain genes; non-Hodgkin lymphoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • Female
  • Genes, bcl-2
  • Humans
  • Induction Chemotherapy
  • Lymphoma, Non-Hodgkin / chemistry
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Prednisone / therapeutic use
  • Proto-Oncogene Proteins c-myc / analysis*
  • Rituximab
  • Tomography, X-Ray Computed
  • Vincristine / therapeutic use

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone