• Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial

      Ferreri, A. J. M.; Cwynarski, K.; Pulczynski, E.; Fox, C. P.; Schorb, E.; Celico, C.; Falautano, M.; Nonis, A.; La Rosée, P.; Binder, M.; et al. (2022)
      219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.
    • Results of the IELSG32 trial at a median follow-up of 88 months demonstrate that matrix followed by autologous transplant is associated with excellent survival and neurotolerability in patients with primary CNS lymphoma

      Calimeri, T.; Cwynarski, K.; Pulczynski, E.; Fox, C. P.; Schorb, E.; Steffanoni, S.; Foppoli, M.; Celico, C.; Falautano, M.; Nonis, A.; et al. (2021)
      Introduction: The MATRix regimen (methotrexate, cytarabine, thiotepa, rituximab) significantly improved outcome of pts with primary CNS lymphoma (PCNSL) enrolled in the IELSG32 trial. At a median follow-up of 40 months, both whole-brain irradiation (WBRT) and autologous transplantation (ASCT) were safe and equally effective. However, sound assessment of OS, late complications, incidence of secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of IELSG32 trial at a median follow-up of 88 (IQR 77- 99) months. Methods: pts with untreated PCNSL (18-70 years) were randomly as signed to methotrexate-cytarabine (arm A), or arm A + rituximab (arm B), or arm B + thiotepa (MATRix; arm C). A second randomization assigned pts with responsive/stable disease after induction to WBRT (arm D) or BCNU-Thiotepa-conditioning ASCT (arm E). Treatment effect on cognitive functions and quality of life (QoL) were addressed by IPCG tests panel and EORTC-QLQ. Results: 219 pts were randomized (arm A 75; B 69; C 75). After induction, 167 had responsive/stable disease: 118 were assigned to WBRT (59) or ASCT (59) while 49 were excluded from 2nd randomization. Fifteen pts died of iatrogenic toxicity; 87 (40%) pts remain relapse-free (A 17; B 28; C 42), 14 of them died of unrelated causes (Table 1). Among 117 relapsing pts, 96 died of PCNSL, 7 of salvage therapy complications. Eight pts developed second cancers at 48-96 months from WBRT (5) or ASCT (3). Second tumors and deaths in relapse-free pts or during salvage were not significantly related to treatments (Table 1). Neuropsychological tests showed a significant impairment in attentiveness and executive functions in the WBRT arm, while transplanted pts had a significant improvement in these functions as well as memory and QoL. Pts treated with MATRix showed significantly better PFS (7-year: 20% arm A; 29% arm B; 52% arm C) and OS (7-year: 26% arm A; 37% arm B; 56% arm C). No significant differences were seen between the consolidation arms for either PFS (7-yr: 55% arm D; 50% arm E) or OS (7- yr: 63% vs 57%). Pts treated with MATRix and consolidation had a 7-yr OS of 70%, without a difference between WBRT and ASCT. Conclusions: MATRix was linked to excellent long-lasting outcome. WBRT and ASCT have comparable efficacy. MATRix and ASCT did not result in higher non-relapse mortality or second tumors onset. WBRT led to impairment of specific cognitive functions.