Study Establishes New Standard of Care for Limited Stage DLBCL, Finds Patients Can Skip Radiation

Results from the Intergroup National Clinical Trials Network (NCTN) Study S1001 established 4 cycles of rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) alone as the new standard approach for the majority of patients with limited-stage diffuse large B-cell lymphoma (DLBCL).¹

The preferred treatment for patients with limited stage DLBCL until the release of this study was R-CHOP and radiation therapy. The study, published in the Journal of Clinical Oncology, is the largest prospective study in the US of limited-stage DLBCL in the rituximab era, with the best NCTN results available in this disease subset.

“This can be the new standard of care for limited stage DLBCL patients,” Daniel Persky, MD, associate director for clinical investigations at the UArizona Cancer Center, principal investigator of its Lymphoma Clinical Research Team, and professor of medicine in the Division of Hematology and Oncology at the UArizona College of Medicine – Tucson, said in a press release.² “Many patients can forgo radiation and receive less chemotherapy while still getting excellent results.”

Patients with nonbulky (< 10 cm) stage I or II untreated DLBCL were enrolled in the study and received 3 cycles of standard R-CHOP therapy, then underwent a centrally reviewed interim PET/computed tomography scan (iPET). Participants who had a negative iPET went on to receive 1 additional cycle of R-CHOP, while those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy.

Of the 158 patients enrolled, 132 were found to be eligible for the study and 128 underwent iPET, which was positive in only 14 (11%) of the patients. The 5-year progression-free survival estimate was 87% (95% CI, 79%-92%) and the overall survival estimate was 89% (95% CI, 82%-94%), with iPET-positive and iPET-negative patients experiencing comparable outcomes.

Notably, only 6 patients progressed and 3 died as a result of lymphoma during the study, with a median follow-up of 4.92 years (range, 1.1-7.7 years). However, 11 patients also died as a result of nonlymphoma causes at a median age of 80 years.

“The results were also favorable in subgroups defined by age, [stage modified (Miller) international prognostic index], cell of origin, and histology and were marginally unfavorable for [double protein expressor],” the authors noted.

According to researchers, this study is particularly promising for reducing unintended harmful effects that can be caused by radiation and chemotherapy in this patient population. These effects can be particularly concerning for older patients who may be suffering from, or at risk of, other health conditions as they age. Thus, reducing the toxicity of their cancer treatments may offer significant health benefits and improve their quality of life.

“We serve this population, and tolerance to the treatment is important to them,” Persky explained. “It is much easier to get an older patient through 4 cycles of R-CHOP than it is through 6.”

Moving forward, the investigators suggested that given the small number of patients who required radiation in our study, additional studies are still necessary to confirm this favorable outcome in patients who had a positive iPET and to better recognize the degree to which radiation and radioimmunotherapy contributed to favorable outcomes.

References:

1. Persky DO, Li H, Stephens DM, et al. Positron Emission Tomography–Directed Therapy for Patients With Limited-Stage Diffuse Large B-Cell Lymphoma: Results of Intergroup National Clinical Trials Network Study S1001. Journal of Clinical Oncology. doi: 10.1200/JCO.20.00999

2. Many Non-Hodgkin’s Lymphoma Patients Can Skip Radiation, UArizona Health Sciences Collaborative Study Finds [news release]. Published October 6, 2020. Accessed October 8, 2020. https://uahs.arizona.edu/news/many-non-hodgkins-lymphoma-patients-can-skip-radiation-uarizona-health-sciences-collaborative