Results from the largest prospective study of patients with primary mediastinal B-cell lymphoma (PMBCL) showed that radiation therapy may be omitted in patients who have a complete metabolic response after chemoimmunotherapy. The IELSG37 international study found that these patients may be spared from late toxicities—without compromising their chances of a cure. These findings were presented at the 2023 ASCO Annual Meeting by Emanuele Zucca, MD, and colleagues (Abstract LBA7505).
PMBCL is clinically and biologically distinct from other types of aggressive lymphoma. An aggressive form of diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma appears as a large mass in the center of the chest and is most common in women between 30 and 40 years old. About 2.5% of people with non-Hodgkin lymphoma have this subtype. IELSG37 is the largest prospective study ever conducted in patients with PMBCL, which has a poor prognosis if remission is not rapid, or the disease recurs; it enrolled patients aged 18 to 70 years (median age = 35 years) from more than 13 countries.
Emanuele Zucca, MD
The trial compared mediastinal radiotherapy and observation only in patients who had complete remission of lymphoma on positron-emission tomography (PET)/computed tomography (CT) scans after standard chemoimmunotherapy with an anthracycline and rituximab-containing regimen. Induction chemoimmunotherapy was completed and response assessed in 530 patients; 268 (50.6%) had a complete metabolic response and were randomly allocated to observation (n = 132) or consolidation radiation at 30 Gy (n = 136).
Key Findings
The study found that patients in complete remission had a 99% overall survival rate at 30 months from random assignment, regardless of whether they received radiotherapy. The additional benefit of radiotherapy in reducing the risk of relapse was minimal, with very similar progression-free survival rates observed in both groups of patients.
Median follow-up time was 63 months (interquartile range = 48–69). Progression-free survival at 30 months was 98.5% in the radiation arm and 96.2% in the observation arm.
The estimated relative effect of radiotherapy vs observation in terms of hazard ratio was 0.47 (0.12–1.89) without adjustments and 0.79 (0.19–3.31) after stratification for the variables used for random assignment. At 30 months, the absolute risk reduction from radiation therapy was 2.3% (–1.5 to 6.2) unadjusted, and 0.8% (–3.0 to 8.3) with stratified hazard ratio.
The most common side effects of the standard chemoimmunotherapy were hair loss; fatigue; sore mouth and throat; and transient reduction of the number of white blood cells (with subsequent risk of infection), platelets (with risk of bruising and bleeding), and red blood cells (anemia). Radiation treatment may lead to heart problems that include ischemic heart disease, high blood pressure, valve problems, and scarring or inflammation of the heart tissue. Radiation fields involving the lung can lead to fibrosis or pneumonitis, as well as restrictive or obstructive lung disease.
“The need to maximize cure rates with initial therapy has made consolidation radiotherapy a historical standard of care, based on the poor results obtained with chemotherapy alone before rituximab and the excellent results shown in trials in which almost all patients underwent irradiation,” said lead author Dr. Zucca, consultant and Head of the Lymphoma Unit at the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland. “However, the long-term toxicities of mediastinal radiotherapy are well documented, particularly second breast, thyroid, and lung cancers, and increased risk of coronary or valvular heart disease, in a patient group dominated by young adults. This study shows chemoimmunotherapy alone is an effective treatment for primary mediastinal B-cell lymphoma and strongly supports omitting radiotherapy without impacting chances of cure.”
Next Steps
Recent studies have shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) can provide excellent results without the use of radiation therapy. Additionally, novel immunotherapies, such as checkpoint inhibitors and chimeric antigen receptor T-cell therapy, are showing promise in patients with relapsed lymphoma.
Researchers are currently exploring the feasibility of a new study to test whether using ctDNA together with PET scans can help drive appropriate treatment decisions in patients who do not have a complete response with initial immunochemotherapy.
Disclosure: The study was funded by the Swiss Cancer League and Cancer Research UK; the Swiss National Science Foundation partially supported the study in Switzerland. For full disclosures of the study authors, visit coi.asco.org.
