ASCO Perspective
“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.
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.
Study at a Glance
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Focus |
Optimizing radiation therapy for primary mediastinal B-cell lymphoma (PMBCL). |
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Population |
545 patients (209 men, 336 women) aged 18 to 70 (median age 35 years) from more than 13 countries. |
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Findings |
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Significance |
PMBCL is clinically and biologically distinct from other types of aggressive lymphoma. An aggressive form of diffuse large B-cell lymphoma (DLBCL), 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. This is the largest prospective study ever conducted on PMBCL, which has a poor prognosis if remission is not rapid, or the disease recurs. 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 option for patients to forgo radiation treatment, as shown in this study, will spare them from unnecessary side effects and cost. |
Key Findings
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. 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 (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 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.”
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.
Next Steps
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.
