Patients with primary central nervous system lymphoma (PCNSL) treated with immunochemotherapy had significantly better overall survival (OS) compared with patients treated with chemotherapy alone (hazard ratio [HR] = 0.75; 95% CI 0.67-0.83), according to an analysis of the National Cancer Database (NCDB). In this study, immunotherapy was defined as treatment with rituximab. The results were published in Blood Advances.
“Our matched survival analysis of patients with PCNSL supports the use of rituximab for these patients, as we demonstrated an OS benefit with the use of immunochemotherapy,” said study author Thomas A. Ollila, MD, of Lifespan Cancer Institute in Providence, Rhode Island. “Interestingly, our study had no clear benefit for patients over the age of 75.”
PCNSL is described by the World Health Organization as an example of primary large B-cell lymphoma of an immune-privileged site. It is uniquely challenging to treat compared to systemic lymphomas because therapies need to penetrate the central nervous system to be effective.
The standard frontline treatment for PCNSL is an induction phase consisting of high-dose methotrexate chemotherapy, which is typically combined with other agents, including rituximab. According to Dr. Ollila, many clinicians include methotrexate and rituximab within a frontline regimen such as R-MPV (rituximab, methotrexate, procarbazine, and vincristine) and MATRix (methotrexate, cytarabine, thiotepa, and rituximab). Following the induction regimen, patients typically receive consolidation with either high-dose chemotherapy and an autologous hematopoietic cell transplant or non-myeloablative chemotherapy, radiation, or maintenance therapy.
Whether rituximab should be included in a frontline regimen for patients with PCNSL remains a question. Two prior large, prospective, randomized clinical trials, the HOVON 105/ALLG NHL 24 phase III clinical trial and IELSG 32, tested the effectiveness of rituximab. The trials had conflicting results, with the IELSG 32 trial showing a benefit from the addition of rituximab to methotrexate and chemotherapy, while the HOVON 105 trial results did not support the addition of rituximab to a methotrexate combination regimen.
“Rituximab does seem to offer a benefit, but the real therapy with curative intent comes from the high-dose methotrexate,” Dr. Ollila said.
To investigate the effectiveness of rituximab for PCNSL, researchers analyzed 4,691 patients, managed in the U.S. between 2013 and 2018, within the NCDB and matched 2,830 patients for the survival analysis. Patients were matched using a one-to-one propensity score to limit possible confounders, and the authors compared the OS in the matched cohort.
The use of immunotherapy increased from 45% in 2013 to 76% in 2018, and immunotherapy use was associated with sociodemographic variables and local (hospital-level) preference rather than clinical factors. The main factors associated with reduced use of immunotherapy included male sex, Black race or Hispanic ethnicity, HIV-positive status, treatment in a lower-volume hospital, and earlier year of diagnosis.
“These results from the analysis stress the importance of ongoing efforts to address disparities in cancer care, as we noted that most differences in giving immunotherapy were treatment center or demographic-related, rather than driven by disease specifics,” said Dr. Ollila.
While patients 75 or younger benefited from the addition of rituximab (HR=0.71; 95% CI 0.63-0.80), the benefit among those older than 75 was not as pronounced (HR=0.87; 95% CI 0.70-1.08).
“As rituximab is an immunotherapy, it could be that this risk-benefit result suggested increased immune senescence among older patients, and rituximab may not be beneficial for these patients,” added Dr. Ollila.
Dr. Ollila noted that the data used for the analysis were gathered before the COVID-19 pandemic. “As rituximab use emerged as a risk factor for serious illness and death from COVID-19, perhaps the OS for patients treated with rituximab in this population would look worse if we were to have data from 2020 to 2023.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Ollila T, Taher R, Moku P, et al. Immunochemotherapy or chemotherapy alone in primary central nervous system lymphoma, a National Cancer Data Base analysis. [published online ahead of print, 2023 Jul 17]. Blood Adv. doi: 10.1182/bloodadvances.2023010352.
