New evidence strongly supports the omission of mediastinal radiotherapy in patients with primary mediastinal B-cell lymphoma (PMBCL) who achieve a complete metabolic response after immunochemotherapy, according to research presented at the International Conference on Malignant Lymphoma 2023.
The International Extranodal Lymphoma Study Group (IELSG37; ClinicalTrials.gov Identifier: NCT01599559) conducted a randomized trial with a non-inferiority design to assess whether radiotherapy can be omitted in patients with PMBCL who achieve a complete metabolic response after immunochemotherapy.
The study included patients with newly diagnosed PMBCL. All patients underwent a standard (rituximab and anthracyclines-based) immunochemotherapy regimen. Complete metabolic response was determined (Lugano classification, Deauville score 1-3) by central review of positron emission computed tomography scans. Patients with complete metabolic response were randomized to observation or consolidation radiotherapy (30 Gy).
The primary endpoint was progression-free survival (PFS). Based on Independent Data Monitoring Committee recommendations, the primary endpoint analysis was performed when ≥80% of patients had a minimum follow-up of 30 months. The secondary endpoint was overall survival at 5 years from registration and long-term toxicity.
After induction immunochemotherapy, 268 of 530 patients (50.6%) achieved a complete metabolic response, with 132 and 136 patients subsequently assigned to the observation and radiotherapy arms, respectively. Baseline characteristics were similar between the arms. Patients had a median age of 35.5 years and were predominantly female (63-65%) in both arms.
At a median follow-up of 5 years, the researchers found no significant difference in 30-month PFS between the radiotherapy arm (98.5%; 95% CI, 94.3-99.6) and observation arm (96.2%; 95% CI, 91.1-98.4; P =.278). The 30-month OS at 5 years was also similar between the arms (99% in both).
Severe cardiac event and secondary malignancies all occurred in the radiotherapy arm, including episodes of left ventricular systolic dysfunction (grade [Gr] 3) and hypertension (Gr 3) as well as 3 secondary malignancies (metastatic melanoma, glioblastoma, and acute myeloid leukemia). There were 3 deaths in the radiotherapy arm (2 infection and 1 secondary malignancy) and 1 death in the observation arm (progressive disease).
“In summary, IELSG37 is the largest randomized trial of primary mediastinal lymphoma ever conducted. Mediastinal radiotherapy can be safely omitted in patients with a metabolic complete response after frontline immunochemotherapy,” concluded the study presenter.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.
Davies, A.J., Zucca, E., Ceriani, L., et al. A randomized trial of observation versus radiotherapy in primary mediastinal B-cell lymphoma patients with complete metabolic response after standard immunochemotherapy. ICML 2023. June 13-17, 2023. Abstract 019.