麻豆传媒

CHICAGO -- Patients with primary mediastinal large B-cell lymphoma (PMBCL) in complete remission following standard chemoimmunotherapy may be able to safely avoid radiation therapy, despite negative findings from a noninferiority trial.

At 30 months, progression-free survival (PFS) rates were similar among patients in PET-confirmed remission after an anthracycline and rituximab-containing regimen whether they continued on to mediastinal radiotherapy or observation alone, though that difference missed statistical significance for noninferiority (98.5% vs 96.2%, respectively, P=0.274), reported Emanuele Zucca, MD, of the Oncology Institute of Southern Switzerland in Bellinzona.

"Due to very few progression events, the noninferiority calculation was not achieved," he told 麻豆传媒. "However, I think it is safe to say that the outcomes for those who had radiation and for those who were assigned to observation were quite similar."

In an adjusted analysis, the number needed-to-treat with radiotherapy reached 126 to prevent one PFS event, according to findings presented at the American Society of Clinical Oncology (ASCO) annual meeting here.

Overall survival at 30 months was essentially identical between the two arms, at 99.3% in the radiation group versus 99.2% in the observation group (P=0.601), Zucca reported at a press conference.

"Mediastinal radiotherapy can be safely omitted in patients with complete remission after frontline immunochemotherapy," he concluded. "Longer follow-up is needed to examine late toxicity. To date, three severe cardiac events and three second cancers have been reported -- all in the patients randomized to radiotherapy."

PMBCL is an aggressive disease that disproportionately affects white women in their 30s, Zucca explained. The disease represents about 5% of non-Hodgkin lymphomas. Patients have a good prognosis if remission is rapidly achieved with initial therapy, with radiation therapy typically used as consolidation.

"The omission of radiation therapy in these patients seems to be safe," said designated ASCO discussant Corey Speers, MD, of Case Western Reserve University and University Hospitals in Cleveland.

"Although radiation has never been safer than it is today, that still puts these women at risk of secondary malignancies, including breast cancer," he said at the press conference. "These are women and patients that are likely to live many more decades, so anything that we can do to eliminate the toxicity of therapy for these women is a win for our field and a win for these patients and their families."

Speers noted that the rates of progression in the study were far lower than expected, which impeded the ability to accurately test for noninferiority with the number of patients enrolled. "We all should be very encouraged by the low event rates in this trial," he said.

The international study enrolled 545 PMBCL patients from 13 countries in North America and Europe -- the majority from Italy. They were treated with standard frontline chemoimmunotherapy. Most received -based regimens, while 17-18% received .

After initial therapy, 268 of the patients who were determined to be PET-negative for cancer were randomly assigned to either observation (n=132) or mediastinal radiation therapy at a dose of 30 Gy (n=136). The radiation treatment had to be initiated within 8 weeks after the negative PET scan. The study's primary endpoint was PFS at 30 months.

Baseline characteristics were similar between the randomized groups. Patients had an average age of 35.5 years, about 64% were women, and over 90% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. A majority had bulky disease (>10 cm), two-thirds had elevated lactate dehydrogenase (LDH), and over 70% were diagnosed as intermediate risk on the Revised International Prognostic Index.

In the radiation arm, six grade 3/4 cardiac events (left ventricular systolic dysfunction, acute heart failure, hypertension) or cases of secondary cancers (glioblastoma, metastatic melanoma, acute myeloid leukemia) occurred, all in patients who had been in complete remission at their last visit. Two of the patients who developed second cancers died.

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