Abstract
Central nervous system (CNS) lymphomas, including primary CNS lymphoma (PCNSL) and secondary CNS lymphoma (sCNSL), are aggressive and challenging diseases with dismal outcomes. Due to its CNS-penetrating properties, ifosfamide, carboplatin, and etoposide (ICE) protocol with or without rituximab has become a frequently used salvage regimen for these lymphomas. However, the short-term efficacy and toxicity of this therapeutic approach as well as its effect on subsequent treatment approaches such as autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CAR-T) therapy, remain limited.
This study aimed to evaluate clinical outcomes following R-ICE therapy in patients with CNS lymphoma.
A retrospective analysis of consecutive adult patients with primary or secondary CNS lymphoma treated with R-ICE at a large tertiary center. Patient demographics, disease characteristics, treatment response, subsequent therapy with ASCT/CAR-T, toxicity, and overall survival (OS) were analyzed.
Twenty-four patients were included with a median age of 71 years (range 33-85), 11 of them females. The majority of patients had newly-diagnosed isolated PCNS lymphoma (62.5%), while the remainder had DLBCL with CNS involvement at the initial diagnosis (12.5%), relapsed/refractory DLBCL (20.8%), and mantle cell lymphoma (MCL, 4.2%). The median number of R-ICE cycles was 2, with 87.5% receiving between one and three cycles. ICE dose reductions were common, with a median dose intensity of 90%. Approximately half of the patients received a reduced ICE dose (<100%). 37.5% of patients proceeded to autologous stem cell transplantation (ASCT), 16.7% received CAR-T cell therapy, and 4.2% underwent allogeneic transplantation. No further treatment was given to 41.7% of patients.
Among all patients, 29% achieved a complete metabolic response (CMR), 33% had a partial response (PR), and 37.5% failed to achieve response. At a median follow-up of 11 months (range: 0–58 months), 75.0% (18/24) of patients had died. A trend toward better 2y-OS was observed among patients who achieved a CMR (2y-OS 57%) compared to those without CMR responses (2y-OS of 17%) (χ²(1) = 2.08, p = 0.150). All CMR patients (100%) proceeded to advanced therapies, including ASCT or CAR-T therapy, whereas only 41% of non-CMR patients transitioned to such treatments (χ²(1) = 4.85, p = 0.028).
Treatment-related toxicity was tolerable. 6 patients (25.0%) demonstrated grade>3 non-hematologic-toxicity (encephalopathy, nausea, cystitis). Early-death (within 30 and 60 dats of ICE initiation) was documented in 35% and 40% of patients, respectively. Prior methotrexate (MTX) exposure did not appear to influence treatment response. The leading cause of death was disease progression, followed by sepsis and one case of CAR-T associated ICANS.
In summary, R-ICE regimen is effective and tolerable in patients with CNS involvement and can serve as a bridge to advanced and potentially curative approaches. These findings support the role of R-ICE in CNS lymphoma and highlight areas for further prospective investigation.
