Patterns of Failure in Patients with Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy

Publication date: Available online 31 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Vasu Tumati, Lakshya Trivedi, Hsiao-Ching Li, Prapti Patel, Pier P. Scaglioni, Madhuri Vusirikala, Navid Sadeghi, Syed Rizvi, Weina Chen, Jason Wachsmann, Robert Collins, Neil B. Desai
PurposeLymphomas 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 radiotherapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiotherapy in unselected diffuse large B-cell lymphoma (DLBCL).Materials/MethodsA retrospective single institution study of all patients diagnosed with 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.ResultsScreening of 275 DLBCL patients yielded a fifty-three 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 following complete response to initial chemotherapy. Of these, 6 (55%) failed at initially involved site(s), and 4 (36%) were isolated initial site relapses. Consolidative radiotherapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95% CI 0.02-0.94, p=0.04).ConclusionDHL/DEL are associated with high relapse rates which preferentially occur at initially involved sites. Amongst patients achieving complete response to chemotherapy, consolidative radiotherapy was associated with improved PFS. This provides a rationale for the continued role of RT in the treatment of DHL and DEL and requires validation in larger cohort.



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