Combining Rituximab, Dexamethasone, Etoposide, Ifosfamide and Carboplatin (R-DeVIC) in Relapsed or Refractory Central Nervous System Lymphoma – a Retrospective Clinical Study

Introduction

High-dose methotrexate (HD-MTX) based first line treatment followed by thiotepa-based high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) has been established as standard of care for eligible untreated patients with primary central nervous system lymphoma (PCNSL) and is also effective in systemic Non-Hodgkin Lymphoma (NHL) with CNS involvement (SCNSL). However, up to one-third of PCNSL patients fail initial treatment or eventually relapse after an initial complete response. In the relapsed/refractory (r/r) setting in PCNSL and in isolated r/r SCNSL, no standard of care is established and outcomes remain poor. The combination of ifosfamide, carboplatin and etoposide with the CD20 antibody rituximab (R-DeVIC) seems promising as all agents have shown efficacy in NHL and can penetrate the blood-brain barrier, but little is known about its feasibility and efficacy in regard to (r/r) CNS lymphoma.

Methods

We retrospectively identified patients by chart review who received at least one cycle of the R-DeVIC regimen for either relapsed or refractory (defined as disease progression within 3 months after end of prior therapy) (r/r) PCNSL or SCNSL with isolated CNS involvement at 3 German sites between January 2010 and June 2023. For SCNSL, treatment lines were counted from the onset of CNS involvement.

The primary endpoint was the overall response rate (ORR), defined as the proportion of patients who achieved complete remission (CR) or partial remission (PR), as assessed by local neuro-radiological evaluation, following R-DeVIC treatment. Secondary endpoints were progression-free survival (PFS), defined as the time from first application of R-DeVIC until progression or death, whichever occurred first, and overall survival (OS), defined as the time from first application of R-DeVIC until death from any cause.

Results

R-DeVIC was applied in 40/80 patients (50%) for r/r disease, respectively. Of the 80 patients, 36 (45%) presented with SCNSL. The median number of prior treatment lines was 1 (range 1-3). 77/80 (96%) of patients had prior treatment with HD-MTX. Median age and Karnofsky Performance Status at R-DeVIC initiation were 63 years (range 35-80) and 80% (range 40-90), respectively. The ORR of R-DeVIC was 52% (10 patients CR, 42 patients PR). The median number of cycles received was 2 (range 1-3). Median PFS and OS rates were 2.5 months (95% CI 1.8-3.1) and 9.0 months (95% CI 6.9-11.1), respectively.

32/80 (40%) patients reached consolidation treatment after R-DeVIC: 22/32 patients (69%) received HCT-ASCT and 5/32 (16%) received CD19-directed Chimeric-Antigen-Receptor (CAR) T cell therapy. In this subset of patients, median PFS and OS rates were 7.7 months (95% CI 6.6-8.1) and 17.4 months (95% CI 7.5-27.3) , respectively.

Conclusions

Our data demonstrate that R-DeVIC is a feasible and effective salvage treatment option in pretreated r/r CNS lymphoma patients. The R-DeVIC regimen enabled 40% of r/r CNS lymphoma patients to enter consolidation strategies, resulting in improved PFS and OS rates.