Long-term Outcomes in Primary CNS Lymphoma After R-MVP and High-Dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplant

Abstract

Background and objectives: Primary CNS lymphoma (PCNSL), a rare CNS malignancy, is usually treated with high-dose methotrexate in the first-line setting, typically followed by consolidation therapy. Due to the broad range of currently available treatments for PCNSL, comparability in long-term follow-up studies is limited, and data are scattered across small studies.

Methods: In this study, we report the long-term survival of patients with newly diagnosed immunocompetent PCNSL, enrolled in a phase II trial from June 2005 to September 2011. Patients were treated using rituximab, methotrexate, vincristine, and procarbazine (R-MVP) chemotherapy followed by high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) in those with partial or complete response to R-MVP. In a post hoc analysis, clinical and imaging features were evaluated in those still alive.

Results: 26 of 32 patients underwent HDC-ASCT consolidation. Of them, 3 patients died of treatment-related toxicity and 2 due to disease progression within 1 year of ASCT. None of the remaining 21 patients had disease progression with a median follow-up of 12.1 years and were included in the analysis. Compared with the post-HDC-ASCT assessment, at the last follow-up, there was no significant difference in the median Karnofsky Performance Status (80 [range: 60-100] vs 90 [range: 70-100]), the median Neurologic Assessment in Neuro-Oncology score (1 [range: 0-4] vs 1 [range: 0-5]), and leukoencephalopathy score (1 [range: 0-3] vs 1 [range: 1-4]).

Discussion: Long-term follow-up demonstrated that treatment was well tolerated in most patients enrolled in this study, with stable leukoencephalopathy on imaging and stable clinical performance status. Disease recurrence was not observed beyond 2 years after HDC-ASCT consolidation.

Figure 1. CONSORT Flow Diagram

Figure 2. Progression-Free Survival and Overall Survival

(A) Kaplan–Meier curves showing progression-free survival (PFS) and overall survival (OS) for all patients who received the intended trial treatment (n = 32). (B) Kaplan–Meier curves showing PFS and OS for transplanted patients (n = 26).

Figure 3. Clinical Parameters During and After HDC-ASCT

(A) The Karnofsky Performance Scale (KPS) at initial enrollment into the trial (initial), after completion of high-dose chemotherapy with stem cell rescue (post-ASCT), and at the most recent follow-up (current) are displayed. (B) The Neurologic Assessment in Neuro-Oncology (NANO) score is a standardized assessment of neurologic function based on the standard domains in the neurologic examination^A8. The scale increases for each domain/severity of abnormality on examination. NANO scores at initial enrollment into the trial (initial), after completion of high-dose chemotherapy with stem cell rescue (post-ASCT), and at the most recent follow-up (current) are displayed.

Figure 4. Leukoencephalopathy During and After HDC-ASCT

(A) Fluid-attenuated inversion recovery (FLAIR) MRI of a representative patient who developed only minimal leukoencephalopathy throughout his treatment and during long-term follow-up. (B) FLAIR MRI of a representative patient with a higher degree of leukoencephalopathy. (C) Displayed are the leukoencephalopathy scores of the study participants on FLAIR MRI after completion of high-dose chemotherapy with stem cell rescue (post-ASCT) and at the most recent follow-up (current). Modified Fazekas score: 0: no white matter abnormalities; 1: mild patchy white matter foci; 2: beginning of confluence of white matter disease; 3: large confluent areas; 4: confluence of white matter abnormalities with cortical and subcortical involvement; and 5: diffuse leukoencephalopathy.