Impact of Myc-Altered Pathology on Radiotherapy Efficacy among Patients with Relapsed/Refractory Large-B Cell Lymphoma: A Collaborative Retrospective Study

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<h3>Purpose/Objective(s)</h3> Presence of <i>MYC, BCL2</i>, and/or <i>BCL6</i> translocations (i.e., double/triple-hit lymphoma [DHL/THL]) among patients with large cell lymphoma (LCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. <h3>Materials/Methods</h3> This retrospective, multi-institutional, international cohort included 211 patients with LCL and known DHL/THL status, who received RT in the relapsed/refractory (r/r) setting. Only the first RT course was included. Separate analyses were conducted for curative versus palliative intent. Response was defined as a radiographic or clinical complete or partial response (PR). Primary chemorefractory disease was defined as less than a PR to initial chemotherapy. Predictors for response and local recurrence (LR) were evaluated using Cox regression analysis. LR analyses and estimates were restricted to patients treated with curative intent to ensure adequate follow-up (median 39.6 months among surviving patients). <h3>Results</h3> Patients were heavily pretreated prior to RT (25% stem cell transplant, 8.5% CART, 41% >2 lines of therapy); 49% were irradiated with curative intent. Most patients (90% curative, 100% palliative) had macroscopic disease at RT. Response rates were similar among those with versus without DHL/THL pathology: 71.4% vs 81.2% (curative), 54.5% vs 64.7% (palliative). DHL/THL was not associated with response on univariate analysis in either the curative (HR 1.03, 95% CI 0.58-1.84, p=.91) or palliative setting (HR 1.42, 95% CI 0.73-2.76, p=.29). In contrast among patients irradiated with curative intent, presence of DHL/THL pathology was associated with increased LR risk (HR 2.38, 95% CI 1.15-4.92, p=.02), controlling for primary chemorefractory disease and radiation biologically effective dose (BED10). LR at 6 and 12 months was 21% and 30% among non-DHL/THL and 41% and 45% among DHL/THL, respectively. <h3>Conclusion</h3> R/R LCL is radioresponsive. Though presence of DHL/THL pathology does not appear to impact RT <i>response</i>, it is associated with increased LR risk, suggesting that it may influence radiation <i>sensitivity</i>. These findings require confirmation in other cohorts.