Impact of Myc-Altered Pathology on Radiotherapy Efficacy Among Patients with Relapsed/Refractory Large-B Cell Lymphoma: A Collaborative Study by XXX: Impact of double hit pathology on RT efficacy.

Abstract

Purpose: Presence of MYC and BCL2 translocations (i.e. double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy.

Methods/materials: Patients with LBCL that received their first course of RT for relapsed/refractory (r/r) disease between 2008-2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per WHO (5^th edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up.

Results: 383 patients (102 DHL, 281 non-DHL, 44% curative) were treated to 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post stem cell transplant. Median biological equivalent dose (alpha/beta 10) was 28 Gy (range 3.2-60.0) for palliative and 46.9 Gy (range 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI 1.05-3.67,p=.03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative).

Conclusions: Relapsed/refractory LBCL remains radioresponsive with 60-80% response rate to RT. While DHL pathology does not appear to influence RT response, its presence is associated with higher rates of local recurrence, suggesting it may be more radioresistant.