Radiotherapy consolidation post-autologous stem cell transplant in Relapsed/Refractory aggressive non-Hodgkin lymphoma improves progression-free and overall survival in patients with partial but not complete metabolic response pre-transplant

Abstract

Abstract Background: Salvage chemotherapy followed by autologous stem cell transplant (ASCT) is a potentially curative procedure for patients with relapsed/refractory (R/R) aggressive non-Hodgkin lymphoma (NHL). To improve long-term outcomes, the International Lymphoma Radiation Oncology Group (ILROG) guidelines recommend the use of radiotherapy (RT) after ASCT for limited stage relapse, sites of bulk, and sites with partial metabolic response (PMR) prior to transplant. However, there are limited data supporting this recommendation in the PET era. Our study objective was to evaluate whether consolidative RT per the ILROG guidelines improves progression-free survival (PFS) and overall survival (OS), compared to patients not receiving consolidative RT. Methods: Retrospective single centre study of patients receiving ASCT between October 2014 and December 2024. Inclusion criteria: adults ≥18 years with histological diagnosis of aggressive NHL (B- or T-cell) who received salvage chemotherapy (anthracycline or platinum-based) with pre-ASCT PET demonstrating complete metabolic response (CMR, Lugano 2014 criteria) with limited stage disease or baseline bulk (≥5 cm), or PMR with one residual avid site. To prevent immortal time bias, we only included patients without progression ≥6 weeks following ASCT so they would have been eligible for RT. The exposure variable was consolidative RT. Outcomes included PFS and OS from ASCT. Survival probability and effect sizes were calculated using Kaplan-Meier method and cox regression. Sensitivity analyses were conducted including only patients without progression >90 days following ASCT, with a residual nodal mass ≥2 cm, and assessing the impact of post-ASCT metabolic response in patients with a post-ASCT PET within 90 days (PMR cohort only). A two-sided p-value of 0.05 was considered significant. Results: Out of 424 patients receiving ASCT, we included 172 (92 PMR (57 received RT), 80 CMR (11 received RT)). Median age was 60 years (IQR 49-66) with 38% female patients. In the PMR cohort, baseline characteristics (age, sex, T or B-cell origin, timing of relapse, stage, international prognostic index risk score, bulk, Deauville score) did not differ significantly between RT and non-RT patients. In the CMR cohort, patients receiving RT were younger compared to those who did not, but there were otherwise no differences in baseline characteristics. Median dose of RT was 35 Gy (IQR 30-36 Gy) over 20 fractions. Median follow-up was 688 days (IQR 330-1605). In the PMR cohort, patients receiving RT had significantly higher 2-year PFS (72% (95% CI 60-84) vs. 25% (95% CI 10-40), HR 0.19 (95% CI 0.11-0.35), p<0.0001) and OS (78% (95% CI 67-90) vs. 59% (95% CI 41-76), HR 0.32 (95% CI 0.15-0.65), p=0.002) than patients who did not. In the CMR cohort of patients with limited stage disease or bulk (>5 cm), there were no significant differences in 2-year PFS (74% (95% CI 43-100) vs. 66% (95% CI 54-77), HR 0.41 (95% CI 0.10-1.74), p=0.2) or OS (71% (95% CI 38-100) vs. 75% (95% CI 64-87), HR 0.61 (95% CI 0.14-2.65), p=0.5) between RT and non-RT patients. In subgroup analysis, a trend towards improved 2-year PFS was observed in patients receiving RT for limited stage relapse (N=8) (100% vs. 73% (95% CI 59-87), p=0.08), though this did not reach statistical significance. There was no difference in 2-year PFS for patients receiving RT for bulk in CMR (N=5) compared to those who did not (57% (95% CI 39-75) vs. 55% (95% CI 37-73), p=0.7). The primary outcome of PFS did not change in sensitivity analyses including only patients without progression >90 days following ASCT, with a residual nodal mass ≥2 cm, or considering post-ASCT metabolic response. In patients with PMR with disease relapse, the most common site of relapse was both in-field/out-of-field for patients receiving RT (35%), whereas for patients not receiving RT the most common sites were both in-field (37%) and in-field/out-of-field (37%). In patients with CMR with disease relapse, the most common site of relapse was out-of-field for patients receiving RT (100%), and in-field for patients not receiving RT (33%). Conclusion: Our data represent a sizable cohort of patients meeting ILROG guidelines for post-ASCT consolidation RT. RT consolidation appears to significantly improve PFS and OS in patients with PMR in one site. RT does not appear to benefit patients in CMR with limited stage or bulk, but analyses were limited by sample size and power.