For patients with gastric MALT (mucosa-associated lymphoid tissue) lymphoma, an “ultra-low dose” of radiotherapy was as effective as the higher, standard dose in providing local control and freedom from distant relapse, researchers from The University of Texas MD Anderson Cancer Center reported at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition.1
“This is the first prospective study evaluating a response-adapted approach with ultra-low–dose (4 Gy) radiotherapy for patients with gastric MALT lymphoma. A complete response to 4 Gy was achieved by 83% of patients. After an additional 20 Gy, all experienced a complete response,” said Jillian R. Gunther, MD, PhD, Associate Professor, Department of Radiation Oncology, MD Anderson Cancer Center, Houston.
There was one relapse, and this patient was effectively salvaged with 20 Gy. The rates of local control and freedom from distant relapse at 3 years were both 96%.
“Radiation therapy is the preferred treatment for stage I to II Helicobacter pylori–negative gastric MALT lymphoma, based on rates of high complete response and local control in patients receiving 24 to 30 Gy over 2.5 to 4 weeks. Although moderate, these radiotherapy doses may still be associated with acute and late toxicities. Given the excellent prognosis for patients with MALT lymphoma, especially gastric MALT, there is interest in treatment de-escalation,” Dr. Gunther said. The benefits of ultra-low–dose, response-adapted therapy, she added, are minimal toxicity, convenience for patients (2 days of treatment), reduced financial burden, and minimal interruption in any systemic treatment plan.
A complete response to 4 Gy was achieved by 83% of patients. After an additional 20 Gy, all experienced a complete response.— Jillian R. Gunther, MD, PhD
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Background
Previously, the randomized phase III noninferiority FoRT trial compared outcomes with 24 Gy and 4 Gy in follicular and marginal zone lymphomas, concluding that 24 Gy is preferred.2 However, in the marginal zone subset, the 88% local progression–free rate achieved with 4 Gy (as compared with 70% in follicular lymphoma) led the authors to conclude the superiority of 24 Gy has not been established in this subtype, Dr. Gunther explained.
These findings led the investigators to propose a response-adapted approach, wherein patients receive 4 Gy initially and only those with an incomplete response receive an additional 20 Gy. After showing this approach was safe and effective in stage I indolent B-cell lymphoma involving the orbit, they evaluated ultra-low–dose (4 Gy) gastric radiation in patients with marginal zone lymphoma involving the stomach. Efficacy was measured as complete gastric response 1 year after treatment.
Study Details
The study’s 24 patients had stage I to IV newly diagnosed or relapsed gastric MALT lymphoma involving the stomach who were H pylori–negative by immunohistochemistry (with additional confirmatory testing in 71%). In 15 patients, translocation 11;18 was tested, and 17% were positive. Pretreatment positron-emission tomography (PET) and computed tomography (CT) were performed on 21 patients, showing avid disease in 6.
Patients received 4 Gy in two fractions to the entire stomach. Response was assessed at 3 to 4 months and again at 6 to 9 months (to allow time for a complete response). Complete responders were followed with observation, whereas patients with partial responses, minimal responses, stable disease, or progressive disease received an additional 20 Gy in 10 fractions. Median follow-up was 36 months.
Effectiveness of Ultra-Low–Dose Radiotherapy
For the 24 patients, 20 (83%) experienced a complete response to 4 Gy at 1 year, at a median time to response of 4 months. Four patients required an additional 20 Gy to treat residual disease, including two patients with stable disease at 3 to 4 months and two patients with persistent disease at 10 to 12 months. “All patients are now in complete response after a total dose of 24 Gy,” Dr. Gunther said.
The 3-year local control rate of 96% reflects one local failure, which occurred 13 months after an initial complete response with 4 Gy of radiation. This patient was salvaged with 30 Gy and again experienced a complete response. The rate of freedom from distant relapse at 3 years was also 96%, which represents one patient with stage IV disease who experienced distant relapse after a confirmed complete response to 4 Gy in the stomach. This patient had transformation to diffuse large B-cell lymphoma at the time of relapse and is now in complete response after systemic therapy, she reported.
Gastrointestinal-related symptoms are common in this population, and 18 patients (75%) experienced these adverse events after treatment. All 18 reported some symptom improvement or resolution. There were no grade ≥ 3 toxicities.
KEY POINTS
- Gastric MALT (mucosa-associated lymphoid tissue) lymphomas may be effectively treated with a response-adapted approach, wherein patients receive 4 Gy of radiotherapy, and patients not achieving a complete response receive an additional 20 Gy.
- This approach led to a 96% rate of local control and a 96% rate of freedom of distant relapse.
Other Considerations
Future analyses should look at the impact of t(11;18) with de-escalated therapy, according to Dr. Gunther. Half of the patients known to have t(11;18) alterations required the additional 20 Gy for response, compared with 27% of patients without the translocation.
“We also want to emphasize the importance of response assessment,” she added. For patients in complete response after 4 Gy, the median time to this response was 4 months, whereas for those requiring an additional 20 Gy, the median time to complete response was 9 months (range, 3–12 months and 4–12 months, respectively). “It’s imperative that patients be given sufficient time to respond before they are moved on to the next therapy,” she emphasized.
Dr. Gunther will co-lead a study of this approach in marginal zone lymphoma (all anatomic sites), with the completion radiotherapy dose being 12 Gy instead of 20 Gy. In addition, forthcoming is a randomized trial of response-adapted radiotherapy for 355 patients with stage I to Il follicular and marginal zone lymphomas, with 2-year progression-free survival as the primary endpoint.
DISCLOSURE: Dr. Gunther reported no conflicts of interest.
REFERENCES
1. Gunther J, Xu J, Bhutani MS, et al: Ultra low dose 4 Gy radiation for definitive therapy of gastric MALT lymphoma. 2023 ASH Annual Meeting & Exposition. Abstract 298. Presented December 9, 2023.
2. Hoskin P, Popova B, Schofield O, et al: 4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): Long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol 22:332-340, 2021.
