Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse.
Chiara RusconiChan Yoon Y CheahToby Andrew EyreDavid TuckerPavel KlenerEva GinéLara CrucittiCristina MuziSara IadecolaGabriele InfanteSophie BernardRebecca L AuerChiara PaganiMonika Duglosz-DaneckaHeidi MocikovaTom van MeertenEmanuele CenciniAna Marin-NieblaMichael E WilliamsPiera AngelilloPaolo NicoliAnnalisa ArcariLucia MorelloDonato ManninaOrsola VitaglianoRoberto SartoriAnnalisa ChiappellaRoberta SciarraPiero Maria StefaniMartin DreylingJohn Francis SeymourCarlo ViscoPublished in: Blood (2022)
Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood-brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.
Keyphrases
- blood brain barrier
- free survival
- chronic lymphocytic leukemia
- tyrosine kinase
- high dose
- end stage renal disease
- locally advanced
- newly diagnosed
- ejection fraction
- chronic kidney disease
- squamous cell carcinoma
- stem cells
- clinical trial
- diffuse large b cell lymphoma
- acute lymphoblastic leukemia
- stem cell transplantation
- patient reported outcomes
- skeletal muscle
- rectal cancer
- cross sectional
- type diabetes
- mesenchymal stem cells
- insulin resistance
- adipose tissue
- combination therapy