Short Induction Therapy Followed by High-Dose Chemotherapy and Autologous HSCT Demonstrates Activity for Older Patients With Primary Diffuse Large B-Cell CNS Lymphoma

Phase 2 Data from the MARTA Study

Short induction therapy followed by high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT) is active in selected older patients with primary diffuse large B-cell CNS lymphoma (PCNSL), despite not meeting the trial’s primary efficacy threshold, determined results from the phase 2 MARTA study.

This prospective, single-arm, phase 2 study was completed at 15 research hospitals in Germany and included patients aged 65 years or older with newly diagnosed, untreated PCNSL if they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and were fit for high-dose chemotherapy and autologous HSCT. Between 2017 and 2020, 54 patients started induction treatment and 51 were included in the full analysis set.

Induction treatment consisted of 2, 21-day cycles of high-dose intravenous methotrexate 3.5 g/m² (day 1), intravenous cytarabine 2 g/m² twice daily (days 2 and 3), and intravenous rituximab 375 mg/m² (days 0 and 4). This was followed by high-dose chemotherapy with intravenous rituximab 375 mg/m² (day –8), intravenous busulfan 3.2 mg/kg (days –7 and –6), and intravenous thiotepa 5 mg/kg (days –5 and –4) plus autologous HSCT. The primary end point was progression-free survival (PFS) at 12 months among all patients who met eligibility criteria and began treatment.

Study results demonstrated at the median follow-up of 23 months (interquartile range [IQR] 16.8 to 37.4), 23 (45%) of 51 patients progressed, relapsed, or died. It was noted that the 12-month PFS was 58.8% (80% confidence interval [CI] 48.9 to 68.2; 95% CI, 44.1 to 70.9).

During induction treatment, the most common grade 3 to 5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3 to 5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, which were due to infectious complications.

Elisabeth Schorb, MD, University of Freiburg, Freiburg, Germany, and colleagues concluded, “Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials.”

Source:

Schorb E, Isbell L, Kerkhoff A, et al. High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): A single-arm, phase 2 trial. Lancet Hematol, Volume 11, Issue 3; Published January 29, 2024. doi: doi.org/10.1016/S2352-3026(23)00371-X