It may be possible to spare patients with primary mediastinal B-cell lymphoma (PMBCL) from unnecessary side effects and costs of radiation therapy, according to study results presented at the ASCO Annual Meeting 2023. Researchers of the largest prospective study of PMBCL have found that radiation therapy can be omitted in patients who have a complete metabolic response (CMR) after chemoimmunotherapy. The IELSG37 international study demonstrated that these patients may be able to avoid late toxicities without compromising the chances of cure.
The trial compared mediastinal radiotherapy and observation only in patients who had complete remission of lymphoma on PET/CT scans after standard chemoimmunotherapy with an anthracycline and rituximab-containing regimen. The study included 545 patients (209 male, 336 female) aged 18 to 70 years (median age 35 years) from more than 13 countries.
The researchers were able to assess 530 patients who completed induction chemotherapy and found that 268 patients (50.6%) had CMR and were randomly assigned to observation (n=132) or radiation (n=136). The median follow-up was 63 months (interquartile range, 48-69).
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The progression-free survival (PFS) was 98.5% in the radiation arm and 96.2% in the observation arm at 30 months. The estimated relative effect of radiotherapy compared to observation was a hazard ratio (HR) of 0.47 (95% CI, 0.12-1.89) without adjustments and 0.79 (95% CI, 0.19-3.31) after stratification for the variables used for randomization.
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 HR. The study found that patients in complete remission had a 99% overall survival rate at 30 months from randomization, regardless of whether they received radiotherapy.
These findings are notable for several reasons, as standard chemoimmunotherapy causes a host of complications, including cardiotoxicity. Radiation fields targeting the lung can cause fibrosis, pneumonitis, and restrictive or obstructive lung disease.
Study investigator Emanuele Zucca, MD, consultant and head of the Lymphoma Unit at the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland, noted in an email interview about the study that the need to maximize cure rates with initial therapy has made consolidation radiotherapy a historical standard of care.
However, he also stated that the long-term toxicities of mediastinal radiotherapy are well documented. “I truly hope that this study will put an end to the long-lasting controversy about the need for radiotherapy in primary mediastinal lymphoma and will bring about a paradigm shift in clinical practice,” said Dr Zucca.
Recent studies have shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), may provide excellent results without the use of radiation therapy in this patient population. Additionally, checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and other novel immunotherapies are showing promise in patients who have their lymphoma return after treatment.
“The study revealed that the additional benefit of radiotherapy was minimal, as both groups of patients demonstrated very similar progression-free survival rates of over 96% at 30 months after the completion of chemotherapy. Regardless of whether they received radiotherapy or not, 99% of the randomized patients were alive 3 years after study entry,” Dr Zucca said in his interview. “The omission of radiotherapy in patients in remission can not only spare them from the adverse effects associated with this treatment but also reduce the overall cost of treatment while still ensuring a very high probability of cure.”
The researchers are currently planning a 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.
Reference
Zucca E, Davies A, Kryachok I, et al. Observation vs. radiotherapy in primary mediastinal B-cell lymphoma patients with complete response to standard immunochemotherapy: the IELSG37 randomized trial. ASCO 2023. June 2-6, 2023. Abstract LBA7505.
