Patients with Primary Central Nervous System Lymphoma Not Eligible for Clinical Trials: Prognostic Factors, Treatment and Outcome.

Sabine Seidel,Roland Schroers,Agnieszka Korfel,Peter Martus,Michael Weller,Thomas Kowalski,Eckhard Thiel,Alexander Baraniskin,Uwe Schlegel,Michelle Margold

doi:10.3390/cancers13122934

Abstract

Simple SummaryMany patients with primary central nervous system lymphoma (PCNSL) participate in clinical trials. The inclusion criteria for these trials are largely uniform among various trials on first-line treatment. Therefore, there is a lack of data on therapeutic management and prognostic factors for patients not fulfilling these inclusion criteria. Here, we retrospectively analyzed treatment, outcome and prognostic factors of 34 patients of our center who did not fulfill inclusion criteria for clinical trials, and compared those results with data from the largest study of PCNSL patients, the G-PCNSL-SG-1 (German PCNSL Study Group 1) trial.Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1–141) in non-study patients and 51 months (1–105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) < 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0–21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0–45)/21 months (95% CI 18–25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.

Highlights

Primary central nervous system lymphoma (PCNSL) is a highly aggressive diffuse large B-cell lymphoma that accounts for 1.9% of primary brain tumors [1]
Adequate renal function is a prerequisite for the application of high-dose methotrexate (HDMTX), which is the backbone of efficient chemotherapy protocols in PCNSL
30 patients were treated within a formal clinical trial, and 40 patients were included in a prospective registry

Summary

Introduction

Primary central nervous system lymphoma (PCNSL) is a highly aggressive diffuse large B-cell lymphoma that accounts for 1.9% of primary brain tumors [1]. A fraction of patients does not meet inclusion criteria for clinical trials. For this patient group, no treatment standard exists, and prognosis is usually poor. Patients with a glomerular filtration rate (GFR) < 50 mL/min [6,7,8,11] (in some trials < 60 mL/min [2,3,4,10,14]) are not eligible for HDMTX and are excluded from clinical trials, including HDMTX-based chemotherapy. While some clinical trials do not consider patients with an ejection fraction (EF) of < 45% [4] or < 50% [8,10,11] or heart insufficiency NYHA (New York Heart Association classification of heart disease) class III b or IV [2,3], others exclude patients with “severe heart diseases” [7,12,13]

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