MTX-based Chemotherapy Combined with Low-Dose, Whole-Brain Radiotherapy Improves Progression-free Survival for Patients with Newly Diagnosed CNS Lymphoma

May 29 2020

The addition of low-dose, whole-brain radiotherapy (LD-WBRT) to a MTX-based combined chemotherapy regimen consisting of rituximab, methotrexate, procarbazine, vincristine, and cytarabine (R-MPV-A) improved progression-free survival outcomes in patients with primary central nervous system lymphoma (PCNSL) on the NRG Oncology clinical trial NRG-RTOG 1114. These results were recently orally presented during the virtual Annual Meeting of the American Society for Clinical Oncology.

Data from a prior phase II, single-arm clinical study suggested that the combination of MTX-based chemotherapy and LD-WBRT was effective in prolonging progression-free survival and had acceptable neurotoxicity (NT) rates, as compared to standard doses of radiotherapy. However, R-MPV-A had not been previously tested without radiotherapy, and the contribution of the LD-WBRT to the favorable outcomes was uncertain. NRG-RTOG 1114 addressed this question by comparing R-MPV-A treatment with and without the addition of LD-WBRT. The goal was to determine if radiotherapy played a role in the observed disease control, and to characterize differences in NT between the treatment arms.

“MTX-based chemotherapy has been proven effective in PCNSL, however, the combined chemotherapy treatment tends to carry severe risk for neurotoxicity to patients. It was crucial to have a study such as NRG-RTOG 1114 conducted to determine if the addition of a low-dose of radiotherapy to the chemotherapy regimen could provide a progression-free survival benefit, and at the same time avoid severe neurotoxicity,” stated Antonio Omuro, MD, Director of the Brain Tumor Center at Smilow Cancer Hospital, Chief of Neuro-Oncology at Yale Cancer Center, and the lead author of the NRG-RTOG 1114 abstract.

NRG-RTOG 1114 accrued 87 evaluable patients and randomly assigned them to receive either R-MPV-A at 3.5g/m2 infused over 2 hours with LD-WBRT of 23.4Gy (chemoRT) or R-MPV-A alone (chemo). Patients exhibited response rates of 81% (ChemoRT) and 83% (chemo) following R-MPV-A. At the median follow up of 55 months, the median PFS was 25 months in the chemo arm and it was not reached in the chemoRT arm (hazard ratio 0.51, p=0,015). The 2-year PFS was 54% (chemo) and 78% (chemoRT). Median overall survival rates were not reached in either treatment arm, however, longer-term survival data are still being collected. NT rates were not statistically significantly increased between treatment arms and both arms had similar rates of grade 3 or higher toxicities including anemia (27% overall), lymphopenia (41%), neutropenia (35%), thrombocytopenia (26%), ALT (23%) and AST (13%). One patient died from sepsis (chemo arm).

The study met its primary endpoint of demonstrating the improvements in progression-free survival. However, investigators cautioned that further neuropsychological testing and neuroimaging analyses are still ongoing to fully characterize cognitive decline associated with this treatment.

This project was supported by grants U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI). This project is funded, in part, under a Grant with the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions.


Omuro A, DeAngelis LM, Karrison T, Bovi JA, Rosenblum M, Corn B, Correa D, Wefel JS, Aneja S, Grommes C, Schaff L, Waggoner SE, Lallana E, Werner-Wasik M, Iwamoto FM, Robinson TJ, Donnelly ED, Struve T, Won M, Mehta M. Randomized Phase II Study of Rituximab, Methotrexate (MTX), Procarbazine, Vincristine, and Cytarabine (R-MPV-A) With and Without Low-Dose Whole-Brain Radiotherapy (LD-WBRT) for Newly Diagnosed Primary CNS Lymphoma (PCNSL). Abstract presented at the virtual Annual Meeting of the American Society of Clinical Oncology (ASCO).

About NRG Oncology

NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG). The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.

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