Consolidative HCT-ASCT Improves PFS In Newly-Diagnosed PCNSL

The MATRix/IELSG43 trial was an international randomized phase 3 trial comparing high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) with non-myeloablative consolidation in patients (pts) with newly diagnosed primary central nervous system lymphoma (PCNSL).

The study was conducted in 79 centers across five countries. The focus was on untreated PCNSL patients aged 18-65, irrespective of their ECOG PS status, with pts aged 66-70 with ECOG PS ≤ 2 also eligible. Researchers administered four cycles of MATRix during the induction process. MATRix therapy consisted of rituximab 375 mg/m2/d days(d) 0,5; methotrexate 3.5 g/m2 d1; cytarabine 2 × 2 g/m2/d d2,3; thiotepa 30 mg/m2 d4, every three weeks. Stem cell harvest was conducted following cycle 2. Patients who achieved at least a partial response (PR) were randomized. Arm A consisted of two cycles R-DeVIC (375 mg/m2 d0; dexamethasone 40 mg/d d1–3; etoposide 100 mg/m2/d d1–3; ifosfamide 1500 mg/m2/d d1–3; carboplatin 300 mg/m2 d1); and Arm B consisted of HDC-ASCT (BCNU 400 mg/m2 (d-6) and thiotepa 2 × 5 mg/kg/d d-5,-4) The Cox proportional hazards model was utilized to analyze the primary endpoint of PFS.

The study involved 368 pts between July 2014 and August 2019. Out of the 346 patients assigned to arms A and B, 116 had to discontinue the induction treatment due to either toxicity or progressive disease. The median age of the randomized pts was 59 years, with 22% being 65 or older. The induction treatment had a positive response rate of 69% (52% PR, 27% CR). Following consolidation CR rate increased substantially to 65% in arm A and 68% in arm B. Thirteen patients died due to treatment-related toxicity. In contrast, six patients died due to toxicity during consolidation treatment. The follow-up median time was 45 months (range 0.2–86). Patients who received HDC-ASCT treatment had three-year PFS and OS rates of 79% (95% CI 71–86) and 86% (95% CI 78–91), while patients who received R-DeVIC treatment had three-year PFS and OS rates of 53% (95% CI 44–62%) and 71% (95% CI 61–78). There was no difference between the arms in terms of neurocognitive functions.

The phase 3 study proved the effectiveness of consolidating HDT-ASCT and non-myeloablative immuno-chemotherapy for newly diagnosed PCNSL pts. Despite similar ORR following consolidation, HDT-ASCT was significantly associated with improved PFS and OS.

Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_15

Clinical Trial:  https://classic.clinicaltrials.gov/ct2/show/NCT02531841

Illerhaus, G., Ferreri, A., Binder, M., Borchmann, P., Hasenkamp, J., Stilgenbauer, S., Roeth, A., Weber, T., Egerer, G., Ernst, T., Hertenstein, B., Lenz, G., Kobbe, G., Brunnberg, U., Schmidt, C., Kneba, M., Dreyling, M., Möhle, R., Panse, J., . . . Schorb, E. CONSOLIDATIVE HCT-ASCT IS SUPERIOR TO NON-MYELOABLATIVE CHEMO-IMMUNOTHERAPY IN NEWLY-DIAGNOSED PCNSL – UPDATED RESULTS OF THE RANDOMIZED PHASE III MATRIX/IELSG43 TRIAL. Hematological Oncology, 41, 41-43. https://doi.org/10.1002/hon.3163_15