PCNSL

ASH 2017 | Induction Chemo-Immunotherapy with the MATRix Regimen in Patients with Newly Diagnosed PCNSL – a Multicenter Retrospective Analysis on Feasibility and Effectiveness in Routine Clinical Practice

The 59th Annual Meeting & Exposition of the American Society of Hematology (ASH) took place in Atlanta, GA, on December 9–12, 2017. On Sunday December 10th, an oral abstract session was held on “Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Outcomes in Rare Entities: HTLV-1 ATLL, Gray Zone Lymphoma, Primary CNS Lymphoma, and Intravascular DLBCL”. This session was moderated by Daniel Persky, University of Arizona Cancer Center and Alison J. Moskowitz, Memorial Sloan Kettering Cancer Center.

Abstract #376 was presented during this session, titled ‘Induction Chemo-Immunotherapy with the MATRix Regimen in Patients with Newly Diagnosed PCNSL – a Multicenter Retrospective Analysis on Feasibility and Effectiveness in Routine Clinical Practice’ by Elisabeth Schorb, Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Germany. This article is based on data presented at the live session, which may supersede information in the pre-published abstract.

Dr. Schorb began by describing high-dose antimetabolites (methotrexate [MTX] and cytarabine [araC]) as the backbone of induction chemotherapy in patients with primary CNS lymphoma (PCNSL).  The international, randomized, phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial was highlighted. This trial compared different induction chemo(immuno)therapy combinations in patients aged 70 years or younger with newly diagnosed PCNSL. The addition of rituximab and thiotepa to conventional methotrexate–cytarabine combination therapy (the MATRix regimen) was associated with significantly improved response and survival rates, an increase in hematological toxicity, but without higher rates of severe complications. Accordingly, the MATRix combination therapy followed by consolidation high dose chemotherapy and autologous stem cell transplant (HDT-ASCT) or whole-brain radiotherapy (WBRT), is now widely regarded as the new standard chemo-immunotherapy for these patients and as the control group for future randomised trials.

Dr Schorb highlighted that the patients encountered in routine clinical practice are often older and frailer than those who were treated in the IELSG32 trial. Therefore, a retrospective multicenter study was conducted to investigate the clinical outcomes in newly diagnosed PCNSL patients treated with MATRix in routine clinical care. The retrospective cohort included all consecutive patients with newly diagnosed PCNSL who received at least 1 cycle of MATRix chemotherapy in a real-world non-trial setting between 2010 and 2017 at 12 European centers. Main endpoints were feasibility, toxicity, remission status after MATRix therapy, progression-free survival (PFS) and overall survival (OS).

Study Highlights
  • 102 patients with newly diagnosed PCNSL were included in the study with a median age of 60 years (28–76)
  • The MATRix retrospective study patients were older and frailer than the IELSG32 trial patients
  • Thirty patients (29%) would not have met the inclusion criteria of the IELSG32 trial (9 pts: aged > 70 years; 4 pts: aged > 65 years + ECOG PS > 2; 3 pts: ECOG PS > 3; 2 pts: HIV infection; 2 pts: active hepatitis; 2 pts: inadequate organ function; 8 pts: ‘not given’)
  • Patients were evaluated if they had received at least 1 cycle of MATRix chemotherapy: MTX (3.5mg/m2 on day 1, cytarabine (2g/m2 twice daily on days 2 and 3), thiotepa (30mg/m2 on day 4) and rituximab (2 x rituximab 375mg/m2 before and/or after chemotherapy)
  • 69 patients (68%) received the planned 4 MATRix cycles of induction treatment and of these, 59 proceeded (58%) to consolidation treatment. An additional 7 patients underwent consolidation treatment after MATRix cycle 2 or 3
  • Overall response rate (ORR): 79%
    • Complete remission (CR): 36%
    • Partial remission (PR): 43%
    • Stable disease (SD): 4%
    • Progressive disease (PD): 12%
  • Median follow-up of 14 months:
    • 2-year OS: 70%
    • PFS: 62%
  • Although direct comparisons cannot be made, in the IELSG32 trial ORR was 86% and with a follow-up of 55 months, 2-year OS was 68% and 2-year PFS was 62%
Safety
  • Severe infections and PD were the main reasons for treatment interruptions
  • Five patients suffered treatment-related mortality (3 patients after the first cycle due to infectious complications and 2 patients after cycle 2 due to neutropenic sepsis and pulmonary embolism)

Dr. Schorb concluded that the MATRix protocol is feasible and effective in the treatment of newly diagnosed PCNSL in routine clinical practice and can produce similar clinical outcomes to the IELSG32 trial. In experienced centers, MATRix is feasible for selected patients aged > 70 years, but close monitoring and dose reductions should be considered for patients with reduced PS and/or co-morbidities.

References
  1. Schorb E. et al. Induction Chemo-Immunotherapy with the Matrix Regimen in Patients with Newly Diagnosed PCNSL – a Multicenter Retrospective Analysis on Feasibility and Effectiveness in Routine Clinical Practice. Oral Abstract #376: ASH 59th Annual Meeting and Exposition, Atlanta, GA.