Treatment of primary central nervous system lymphoma: high-dose methotrexate alone or with additional therapy?

The aim of this study was to evaluate high-dose (HD) methotrexate (MTX; Trexall) alone and in combination with other therapies for the treatment of primary central nervous system (CNS) lymphoma (PNCSL). The study found that HD-MTX in combination with other chemotherapies was most effective for these patients.

PCNSL involves the brain, spinal cord, and eyes, without any evidence of lymphoma elsewhere. PCNSL is a rare type of non-Hodgkin’s lymphoma (NHL). Treating PCNSL is difficult because a lot of therapeutics cannot cross the barrier to the brain. HD-MTX is a type of chemotherapy (CT) that can enter the brain. It cancer cells and stops them from working properly. With the exception of HD-MTX, no standard treatments exist for PCNSL.

Some studies have shown that giving other therapy after HD-MTX can improve patient outcomes. Additional therapies can include other types of CT, whole-brain radiotherapy (WBRT), or autologous stem cell transplant (ASCT; healthy blood stem cells from the patient to replace bone marrow lost during CT). It is not yet clear what the best combination of therapy is for patients with PCNSL.

This study evaluated data from 31 trials involving patients with PCNSL. Patients were first treated with HD-MTX alone or in combination with 1-4 other types of CT. The study also evaluated the effect of consolidation therapies such as WBRT and ASCT. Consolidation treatments are given after an initial therapy to kill any cancer cells left in the body.

30% of all patients who were given HD-MTX alone had a complete response (CR). Addition of more types of CT increased the number of patients who had a CR. One more treatment added to HD-MTX led to a CR rate of 38%. 2 more treatments added to HD-MTX led to a CR rate of 49%. 

The most effective combination was MPV (HD-MTX, procarbazine, and vincristine) with a CR of 58%. MPV with rituximab (Rituxan) showed a CR of 63%. HD-MTX with rituximab and temozolomide (Temodar) was associated with a CR rate of 60%.

The survival rate for patients who received CT with WBRT consolidation was 55% after 5 years. These patients also had a 41% rate of survival without cancer worsening after 5 years. Patients who were given CT with ASCT consolidation had a 5-year survival rate of 77% and a 5-year survival without cancer worsening rate of 63%.

The study found that HD-MTX combinations such as MVP with or without rituximab followed by ASCT consolidation gave the best outcome for patients with PCNSL. 

The trials evaluated had different treatment schedules and methods and most had a small number of participants. This may have impacted results.