If eligible for high-dose methotrexate (HDMTX)-based chemotherapy, patients with primary central nervous system lymphoma (PCNSL) can have promising outcomes even when not eligible for clinical trials, according to research published in Cancers.

HDMTX-based conventional or myeloablative chemotherapy has improved outcomes for patients with PCNSL. Clinical trials with HDMTX have 2-year overall survival (OS) rates between 32% to 87%.

For patients with PCNSL who do not meet inclusion criteria for clinical trials, no standard treatment exists. Patients may be excluded from trials for low Karnofsky performance status (KPS), comorbidities, immunosuppression, previous malignancy, renal insufficiency and other factors.

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The authors retrospectively analyzed the outcomes and prognostic factors of 34 patients with PCNSL who were ineligible for clinical trials. 27 non-study patients with glomerular filtration rate (GFR) of ≥ 50mL/min received HDMTX as first-line treatment. These patients were compared with outcomes of 526 patients treated in the German PCNSL Study Group 1 trial.

A total of 17 patients treated with HDMTX-based therapy had a complete remission or complete remission unconfirmed (CR/CRu), 6 patients had progressive disease (PD), 2 patients died, and 2 prematurely ended treatment after achieving partial remission (PR).

Median OS for all patients was 6 months, and the 3-year OS was 30.9%. For patients who received HDMTX, the OS was 20 months, with a 3-year OS of 37.4%. Age was a favorable prognostic factor, as well as achieving CR/CRu early, and CR/CRu after therapy completion.

The median OS for patients in clinical trials was 21 months, with a 3-year OS of 38.3%.

Based on these results, intensive chemotherapy could be offered to patients in a compromised clinical state and many patients with at least one exclusion criteria for clinical trials. Patients with severe renal insufficiency are unable to tolerate HDMTX.

Overall outcomes were similar for patients in clinical trials and non-study patients who received HDMTX. However, the authors found a significant difference in favor of the non-study patients once adjusted for age and KPS (HR, 0.48; P =.005).

The authors concluded that the results for high-risk patients who are able to tolerate HDMTX treatment are promising.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Seidel S, Margold M, Kowalski T, et al. Patients with primary central nervous system lymphoma not eligible for clinical trials: prognostic factors, treatment and outcome. Cancers (Basel). 2021;13(12):2934. doi:10.3390/cancers13122934