Outcomes of Patients with Primary Central Nervous System Lymphoma Treated with Matrix Followed By High-Dose Chemotherapy and Autologous Stem Cell Transplant - a Multicentre, Retrospective Study

Background: Methotrexate, cytarabine, thiotepa and rituximab (MATRix) followed by high-dose chemotherapy (HDC) with a thiotepa-containing regimen and autologous stem cell transplant (ASCT) has become standard in Canadian centers for treatment of primary central nervous system lymphoma (PCNSL). However, there remains variation in high-dose chemotherapy regimens used, including thiotepa dosing. In Ontario, Canada's most populous province, patients at Princess Margaret Cancer Centre (PM) until 2021 underwent conditioning with carmustine and thiotepa 10mg/kg divided over 2 days. In December 2021, the thiotepa dose in the conditioning regimen was increased to 20mg/kg divided over 2 days aligning with the IELSG32 trial. At Juravinski Hospital (JH), patients are treated with busulfan (9.6mg/kg over 3 days) and thiotepa 600mg/m2 over 2 days. In a 70kg patient, with 1.9m2 BSA this would result in a 50% reduced dose of thiotepa at PM prior to December 2021, and a 17% reduced dose of thiotepa if treated at JH, compared to PM from December 2021 onwards (the IELSG32 dosing). Aim: As it is not clear if differences in thiotepa dosing impact clinical outcomes, we aimed to assess overall survival (OS), progression-free survival (PFS) and transplant toxicities of patients treated with MATRix followed by three different HDC regimens and ASCT at 2 large transplant centres in Ontario, Canada. Methods: We performed a retrospective review of patients with PCNSL treated with MATRix followed by HDCT and ASCT from 2017-2022 at PM, and from 2017-2020 at JH. Patients were included if they were >18 years, treated with MATRix first-line or for relapsed/refractory disease, and underwent consolidation with ASCT. Data on stem cell collection, conditioning regimen, and transplant toxicities were collected. OS and PFS were calculated using Kaplan-Meier method, and Cox regression analysis was used to assess the impact of patient and treatment variables on outcomes. Results: At PM and JH, 52 patients were treated with MATRix followed by HDC and ASCT and were included: 18 at JH with busulfan and thiotepa 600mg/m2 over 2 days (Cohort 1), 23 at PM with carmustine and thiotepa 10mg/kg over 2 days (Cohort 2), and 11 at PMCC with carmustine and thiotepa 20mg/kg over 2 days (Cohort 3). Patients were followed for a median of 26 months, 41 months and 15 months, respectively. There were no differences between cohorts in age or use of MATRix as first-line therapy. Most patients achieved a complete response (CR) or partial response (PR) on pre-ASCT MRI (83% in cohort 1, 87% in cohort 2, 100% in cohort 3, p=0.592). One patient in cohort 1 and 1 in cohort 2 had progressive disease after MATRix requiring salvage chemotherapy prior to ASCT. The median number of CD34+ cells infused per kg was 4.7 in cohort 1, 3.45 in cohort 2, 6.04 in cohort 3, p=0.036. Patients in cohorts 1 and 3 had higher rates of febrile neutropenia compared to patients in cohort 2 (94.4% and 81.8% compared to 65.2%, p=0.014). Median days to neutrophil recovery and platelet count recovery were similar (p=0.292 and 0.226 respectively). CR after ASCT was achieved in 13/18 patients (72%) in cohort 1, 13/23 patients (57%) in cohort 2 and 8/11 patients (73%) in cohort 3, p=0.288. The 18-month OS was 94.4% in cohort 1, 94.7% in cohort 2 and 90.9% in cohort 3 (p=0.545). The 18-month PFS was 94.1% in cohort 1, 86.3% in cohort 2, and 90.0% in cohort 3 (p=0.790). Over a median follow up of 26 months (range 1-79), there were 8 deaths. Causes of death included progression of lymphoma in 5 patients, infectious complications in 2 (pneumocystis pneumonia and bacterial sepsis), and an unrelated cause in 1 patient. Results from a Cox proportional hazard model showed no impact of baseline demographic features (age, sex, CD34+ cell dose collected), or treatment-related factors (conditioning regimen, achieving CR prior to ASCT, achieving CR after ASCT) on OS or PFS. Conclusion: These data from 2 academic transplant centres shows outcomes with MATRix followed by HDC with a thiotepa-based regimen and ASCT for patients with PCNSL are encouraging. Acknowledging the limited sample size and non-randomized comparison, differences in conditioning regimens including the use of carmustine versus busulfan and thiotepa dosing do not appear to significantly impact outcomes.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.