Results from the largest prospective study of primary mediastinal B-cell lymphoma show that radiation therapy can 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 the chances of cure.

The research was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The study found that patients in complete remission had a 99% overall survival rate at 30 months from randomisation, 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.

Induction chemoimmunotherapy was completed and response assessed in 530 patients; 268 (50.6%) had a CMR and were randomly allocated to observation (132) or radiation (136).  

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 most common side effects of the standard chemoimmunotherapy were hair loss, fatigue, sore mouth and throat, 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 (anaemia).

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 scar tissue (fibrosis) or inflammation (pneumonitis), and 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 Emanuele Zucca, MD, 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.”

“These findings are particularly important for this aggressive type of lymphoma, which occurs more often in young adults. These reassuring data demonstrate that patients with primary B-cell lymphoma who have a rapid response to initial dose-intensive chemoimmunotherapy have excellent outcomes with a very low likelihood of the cancer coming back, regardless of whether they receive consolidative radiation therapy as part of their treatment. This means that these patients can safely forgo radiation and its side effects without compromising survival,” said Corey W. Speers, MD, PhD, ASCO Expert.

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 CAR-T cell therapy, are showing promise in patients with lymphoma that comes back after treatment.

Researchers are currently exploring the feasibility of a new study to test whether using ctDNA (liquid biopsy) together with PET scans can help drive appropriate treatment decisions in patients who do not have a complete response with initial immunochemotherapy.

The study was funded by the Swiss Cancer League and Cancer Research UK; the Swiss National Science Foundation partially supported the study in Switzerland.

Watch Prof Zucca's interview here.

Source: ASCO