Radiation Alone Improves Outcomes in Early-Stage NLPHL Without High-Risk Features

Radiotherapy alone was associated with excellent progression-free survival (PFS) and low rates of late toxicity in patients with stages IA to IIA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and no known high-risk features, according to a retrospective analysis published in Blood. The researchers, led by Michael Binkley, MD, of Stanford University School of Medicine, also found that a variant immunoarchitectural pattern and lymphoma involvement of ≥2 sites were risk factors for lower PFS with a radiotherapy-only approach. The addition of these risk factors to a risk stratification may help in the prediction of patient outcomes.

These findings were based on analysis of patients from 18 institutions with either stage IA (54.9%) or IIA (45.1%) NLPHL. Patients were 16 years of age or older, CD20 positive, and managed by observation, systemic therapy, and/or radiotherapy between 1995 and 2018. Response to treatment was collected from imaging data when available.

The primary endpoints of this study included PFS after primary and salvage therapy, overall survival (OS), and freedom from transformation to large cell lymphoma. Researchers defined PFS as the duration between date of diagnosis and date of recurrent or progressive lymphoma or death from any cause. The investigators also assessed for treatment-related acute and late toxicities.

The median age of the study cohort was 39 years, and the majority of the patients were men (72.3%). In addition, the majority of patients at baseline had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (86.9%). The primary management approaches were as follows:

  • radiotherapy only (n=257; 46.0%)
  • radiotherapy plus chemotherapy (n=184; 32.9%)
  • chemotherapy only (n=47; 8.4%)
  • observation (n=37; 6.6%)
  • rituximab and radiotherapy (n=19; 3.4%)
  • rituximab alone (n=15; 2.7%)

Over a median follow-up period of 5.5 years (interquartile range [IQR] = 3.1-10.1), the overall 5-year PFS was 87.1% (95% CI 83.6-90.0%). The 5-year PFS rates by treatment modality were:

  • radiotherapy only: 91.1% (95% CI 85.3-94.7)
  • radiotherapy plus chemotherapy: 90.5% (95% CI 84.8-94.1)
  • chemotherapy only: 77.8% (95% CI 61.3-88.0)
  • observation: 73.5% (95% CI 50.6-87.0)
  • rituximab and radiotherapy: 80.8% (95% CI 41.0-95.1)
  • rituximab only: 38.5% (95% CI 14.0-62.8)

No difference in 5-year PFS was observed between patients classified as favorable versus unfavorable by German Hodgkin Study Group (GHSG) criteria who were treated with radiotherapy (91.3% vs. 88.9%, respectively; p=0.31) or radiotherapy plus chemotherapy (91.1% vs. 91.3%; p=0.35).

Variant immunoarchitectural pattern and >2 lymphoma-involved sites were associated with significantly lower PFS and higher transformation in the cohort of patients treated with radiotherapy, according to a multivariable analysis (p<0.05).

Approximately 3.8% (n=21) of the overall study population developed transformation to either T-cell rich B-cell lymphoma or diffuse large B-cell lymphoma at a median of 3.6 years (IQR=2.5-7.8) after primary treatment. The median follow-up after transformation was 6.7 years (IQR=1.5-8.8), and the overall 5-year freedom from transformation was 97%. In addition, the 5-year PFS was 62% and the 5-year OS was 89% after diagnosis of transformation.

The 5-year OS across all patients was 98.3% (95% CI 96.4-99.2%). A total of 24 deaths were reported, with 7 confirmed as lymphoma specific. OS was not significantly worse for patients who relapsed within 1 year (p=0.37) or 2 years (p=0.16) of initial diagnosis.

The rates of grade 1 to 3 toxicities were 37.6% for radiotherapy only, 39.2% for radiotherapy plus chemotherapy, 59.3% for chemotherapy only, and 26.3% for rituximab and radiotherapy.

Dr. Binkley told ASH Clinical News that the study was limited by its retrospective nature, as well as the lack of central pathology review. “Outside of a prospective clinical trial, future studies focusing on NLPHL should strive to have central pathology review to confirm diagnosis and score the immunoarchitectural pattern,” he said.


Binkley MS, Rauf MS, Milgrom SA, et al. Stage I-II nodular lymphocyte-predominant Hodgkin lymphoma: a multi-institutional experience of adult patients by ILROG. Blood. 2020 Mar 25. [Epub ahead of print]