Abstract P090

Omission of Radiotherapy is Associated with Inferior Progression-Free Survival in Bulky and Interim-PET-Positive Early-Stage Hodgkin Lymphoma: A Propensity-Matched Multicenter Real-World Analysis

Background: The role of consolidative radiotherapy (RT) in early-stage classic Hodgkin lymphoma (cHL) remains debated, particularly in the era of PET-adapted therapy. We evaluated real-world treatment patterns, outcomes, and toxicity of combined modality therapy (CMT; chemotherapy and RT) v chemotherapy alone.

Methods: We identified 810 consecutive patients with stage I-II cHL treated at eight academic centers between 2012 and 2020. Treatment was analyzed by intention-to-treat. Propensity score matching (PSM) by age, stage, sex, and prognosis (favorable v unfavorable per NCCN) yielded 480 patients for comparison of CMT (N=240) vs chemotherapy alone (N=240). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Subgroups were assessed by disease bulk and interim PET (iPET2) Deauville score (DS).

Results: Median age of the entire cohort was 33 (range 18-84); 436 (54%) were female. By intention-to-treat, 300 (37%) received CMT and 510 (63%) chemotherapy alone, with 90% receiving A(B)VD-based regimens. At median follow-up of 5.4 years, 5-year PFS and OS for the full cohort were 82% and 98%, respectively. In the PSM cohort, 5-year OS did not differ between CMT and chemotherapy alone (99% v 97%; p=0.620), but trended towards improved PFS with CMT (87% v 81%; p=0.053; Fig 1A). CMT improved PFS in bulky disease (92% v 73%; Hazard Ratio [HR] 3.8, 95% CI 1.4-10.2; p=0.005) and iPET2 DS≥4 (75% v 52%; HR 3.0, 95% CI 1.1-7.8; p=0.020; Fig 1B-C). Patients receiving CMT were less likely to relapse at sites of prior disease (7% v 18%; p<0.001). iPET2 DS4-5 was associated with inferior 5-year PFS (46%) v DS1-2 (92%) and DS3 (79%; p<0.001). Among iPET-positive patients, those who received unplanned consolidative RT were less likely to require salvage therapy than those treated with chemotherapy escalation alone (29% v 45%; p=0.037). CMT was associated with higher rates of hyperlipidemia, hypothyroidism, and second malignancy, though 69% of second malignancies occurred outside the RT field. Pulmonary fibrosis was more common with 6 v ≤4 cycles of bleomycin (4% v 0.4%; p=0.008) and when it occurred resulted in worse 5-year OS (50% v 99%; p<0.001).

Conclusion: In this large cohort, CMT and chemotherapy alone yielded comparable OS, but CMT conferred a PFS advantage in bulky or iPET2-positive (DS≥4) disease. These findings support a risk-adapted approach in which consolidative RT is preferentially considered for high-risk subgroup.