Radiotherapy for early stage diffuse large B-cell lymphoma with or without double or triple hit genetic alterations

Abstract

We investigated whether adding radiation (RT) to systemic therapy improved outcomes in early stage diffuse large B-cell lymphoma (DLBCL) patients with or without double- or triple-hit lymphoma (DHL/THL) biology. This analysis included 183 patients profiled with fluorescent in situ hybridization (FISH) for alterations in MYC, BLC2, and/or BCL6. A total of 146 (80%) were non-DHL/THL, 27 (15%) were DHL, and 10 (6%) were THL. Systemic therapy without RT resulted in inferior freedom from relapse (FFR) (HR: 2.28; 95% CI, 1.10–4.77; p = .02). The median FFR for non-DHL/THL was not reached and was 33 and 22.3 months for DHL and THL, respectively; p < .001. Low-risk (R-IPI <2) DHL/THL patients treated with rituximab-based therapy had 3-year FFR rates of 11% and 71% for systemic therapy without and with RT, respectively; p = .04. No differences in overall survival were observed between the treatment groups. Treatment intensification with RT may improve early stage DHL/THL outcomes.

Reply to E. Hawkes et al

“…8 In addition, several studies now suggest that limited-stage presentations of HGBL with rearrangements of MYC and BCL2 or BCL6 have favorable outcomes with standard therapeutic approaches, including R-CHOP-based treatment delivered in S1001. [9][10][11] Finally, we agree with Hawkes et al 1 that radioimmunotherapy requires further study before being incorporated into standard therapy for the few patients with positive interim fluorodeoxyglucose-PET scans after three cycles of R-CHOP. We note the excellent outcomes for PET-positive patients receiving both involved field radiotherapy and radioimmunotherapy but concede that the relative contribution of each of these components cannot be determined.…”

Prognostication of Primary Tumor Location in Early-Stage Nodal Diffuse Large B-Cell Lymphoma: An Analysis of the SEER Database

“…In the present study, we found that TNFRSF14 is downregulated in Sub-DLBCL by analyzing RNA-sequencing data and screening DEGs, which may have a similar biological function to its inactivation of EZB subtypes, explaining the worst outcome of Sub-DLBCL. Considering that COO and MYC/BCL2 status may not influence the outcome among patients with early-stage DLBCL treated with R-CHOP regimen [26][27][28][29][30][31], other factors (internal or external microenvironmental factors) may drive the poor prognosis of early-stage nodal DLBCL located under the diaphragm. This hypothesis, however, needs to be further confirmed in the future, as we only included early-stage nodal DLBCL patients while only RNA-sequencing data were analyzed and not DNA sequencing.…”

Impact of Double- or Triple-Hit Pathology on Rates and Durability of Radiation Therapy Response Among Patients With Relapsed or Refractory Large B-Cell Lymphoma

“…Despite the chemorefractory nature of DHL/THL, recent retrospective studies 31,32 have shown improved locoregional control in patients with DHL/THL that underwent consolidative RT after induction immunochemotherapy compared with patients who received chemotherapy alone. These studies suggest efficacy of RT in those patients with chemosensitive disease.…”