Rituximab and Thiotepa Improves Outcomes in Primary CNS Lymphoma Patients

Rituximab and Thiotepa Improves Outcomes in Primary CNS Lymphoma Patients

During the recent International Conference on Malignant Lymphoma in Lugano, Switzerland, researchers from the International Extra-nodal Lymphoma Study Group (IELSG) led by Andrés Ferreri, MD, Ospedale San Raffaele, Milano, Italy, presented their latest results showing that the addition of thiotepa and rituximab to antimetabolites significantly improves outcomes in primary CNS lymphoma patients.

The study was conducted at 52 locations across five countries and it enrolled patients with clinically confirmed PCNSL, randomizing them into one of the three following treatment groups:

  • 75 patients were given four 3-week cycles of methotrexate at 3.5 g/m2 on day 1 and cytarabine at 2 g/m2 twice daily on days 2 and 3
  • 69 patients were given four 3-week cycles of methotrexate at 3.5 g/m2 on day 1 and cytarabine at 2 g/m2 twice daily on days 2 and 3, in combination with 375 mg/m2 of rituximab on day 5
  • 75 patients who made up the MATRIX group, were given four 3-week cycles of methotrexate at 3.5 g/m2 on day 1 and cytarabine at 2 g/m2 twice daily on days 2 and 3, combined with rituximab at the same dose plus 30 mg/m2 of thiotepa on day 4

The researchers utilized patient stem cells, histology and neuroimaging reports to assess the rates of complete remission and treatment failure among all different groups.

Primary findings showed that in this study patients’ overall survival and absence of treatment failure were improved with the MATRIX regimen compared with either methotrexate/cytarabine alone or in combination with rituximab. Other important findings included:

  • A greater percentage of patients who received the MATRIX regimen achieved complete remission.
  • The most often reported adverse study event was infection, and complications that arise from it; although the number of events reported were similar in each treatment group
  • There were 21 patient deaths due to chemotherapeutic toxicity with no significant differences in the number of deaths by treatment group.

In a conference press release Dr. Ferreri, stated “Conventional chemoradiotherapy is associated with suboptimal disease control and a high risk of neurotoxicity. In the search for new active drugs, there are suitable candidates. Rituximab has changed the natural history of diffuse large B-cell lymphoma but it is doubtful that it can cross the blood-brain barrier. Tiotepa is active against aggressive lymphomas and is able to cross the blood-brain barrier.”

Dr. Ferreri’s colleague, Dr.Tracy T. Batchelor MD, MPH, Professor of Neurology, Harvard’s Dana Farber Institute, added,  “There is a dire need for new agents to treat PCNSL. This was a well-conducted study, particularly since randomization was stratified by IELSG scores, which were balanced across treatment arms; the IELSG has raised the bar for randomized trials in our field.”

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