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Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy
Vasu Tumati1, Lakshya Trivedi1, Hsiao-Ching Li2
1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Purpose:
Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL).
Methods And Materials:
A retrospective single-institution study of all patients with diagnoses of non-Hodgkin lymphoma between 2011 and 2015 was performed. DHL status was determined by fluorescence in-situ hybridization, and DEL status was determined by immunohistochemistry. Progression-free survival (PFS) was calculated from the end of chemotherapy using the Kaplan-Meier method. Cox modeling was used for multivariable analysis.
Results:
Screening of 275 DLBCL patients yielded a 53-patient cohort, including 32 patients with DHL, 10 with DEL, 9 with a triple rearrangement, and 2 triple expressors. Of the 26 patients whose disease progressed, 15 had primary refractory disease. The remaining 11 failures were relapses after complete response to initial chemotherapy. Of those failures, 6 (55%) occurred at initially involved site(s), and 4 (36%) were isolated initial site relapses. Consolidative radiation therapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95% confidence interval 0.02-0.94, P = .04).
Conclusions:
DHL/DEL are associated with high relapse rates, which preferentially occur at initially involved sites. Among patients achieving complete response to chemotherapy, consolidative radiation therapy was associated with improved PFS. This provides a rationale for the continued role of radiation therapy in the treatment of DHL and DEL and requires validation in a larger cohort.
Insights
Double-hit (DHL) and double-expressor (DEL) lymphomas have high relapse rates. Consolidative radiation therapy significantly improved progression-free survival (PFS) in patients achieving complete response to chemotherapy.
Area of Science:
- Hematology
- Oncology
- Radiation Oncology
Background:
- Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangements (double-hit, DHL) or MYC and BCL-2 overexpression (double-expressor, DEL) show poorer outcomes with standard immunochemotherapy.
- Optimal treatment strategies for DHL/DEL lymphomas remain unclear, with limited data on consolidative radiation therapy's role.
- Understanding relapse patterns is crucial for refining treatment approaches in these aggressive lymphomas.
Purpose of the Study:
- To investigate patterns of treatment failure in DHL/DEL lymphomas.
- To assess the impact of initial disease sites on relapse patterns.
- To evaluate the contribution of consolidative radiation therapy to outcomes in DLBCL patients with DHL/DEL.
Main Methods:
- Retrospective analysis of 53 DLBCL patients (2011-2015) diagnosed with DHL, DEL, or triple rearrangements/expressors.
- DHL/DEL status determined by fluorescence in-situ hybridization and immunohistochemistry.
- Progression-free survival (PFS) analyzed using Kaplan-Meier and Cox multivariable models.
Main Results:
- Of 53 patients, 32 had DHL, 10 had DEL, and 11 had triple abnormalities. 26 patients experienced disease progression.
- Relapses occurred preferentially at initially involved sites (55% of failures).
- Consolidative radiation therapy was significantly associated with improved PFS (HR 0.17, P=.04).
Conclusions:
- DHL/DEL lymphomas exhibit high relapse rates, often at primary disease sites.
- Consolidative radiation therapy demonstrates a significant benefit in improving PFS for patients achieving complete response.
- These findings support a continued role for radiation therapy in managing DHL/DEL lymphomas, warranting further validation.
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