Real World Data on Ibrutinib Use in PCNSL Rel/Ref

Historically, HDCT followed by ASCT has not been considered a feasible option for elderly patients, although recent data collected in the "real life" setting and a pilot study conducted in Germany demonstrate that maintenance of the dose intensity of HD-MTX and treatment completion with HDCT / ASCT-based consolidation are similar to those in clinical studies. However, 20 to 50% of newly diagnosed PCNSL patients do not achieve a complete response with currently available treatment regimens, highlighting the need for improved induction strategies. Furthermore, even after a complete response, patients with PCNSL may experience relapse, especially in the elderly. First-line treatment failure usually occurs (70-75% of cases) within the first two years and the prognosis of this population is extremely poor as demonstrated in a retrospective study of more than 250 patients with PCNSL R / R who reported median PFS and OS at first relapse / progression of 2.2 and 3.5 months, respectively. Similar results have also been highlighted in several prospective studies in which the PFS and OS curves are equivalent. There is currently no standard of treatment for the treatment of patients with PCNSL R/R. Data extrapolated from the long-term FU of a randomized phase 2 trial suggests that patients with relapses more than 36 months after the end of first-line methotrexate-based immuno-chemotherapy could benefit from a rechallenge with the same treatment. On the other hand, for patients refractory or with relapses within 36 months or not eligible for HD-MTX, the best therapeutic choice is represented by enrollment in a clinical trial. In the absence of this option, the therapeutic choice is based on the experience of phase 2 studies.

Inclusion criteria

• Histological or cytological diagnosis of DLBCL
• Disease localized exclusively in the CNS (brain, meninges, cranial nerves, eyes and / or spinal cord) both at first diagnosis and at failure
• Progressive or recurrent disease
• Previous treatment with high-dose methotrexate-based chemotherapy ± WBRT
• Age 18 - 80 years
• ECOG performance status 0-3
• Adequate hematopoiesis (platelets> 25,000 / mm3, hemoglobin> 8 g / dL, ANC> 1,000 / mm3), renal (serum creatinine <2 times UNL and creatinine clearance ≥40 mL / min), cardiac (VEF ≥50% ) and liver function (SGOT / SGPT <3 times UNL, bilirubin and alkaline phosphatase <2 times UNL).
• Patients who have been given treatment with ibrutinib, alone or in combination with immunochemotherapy, and who have or have not received the same.

Exclusion criteria

• Patients with concomitant extra-CNS disease at presentation or relapse
• Symptomatic coronary heart disease, cardiac arrhythmias not well controlled with drugs, or myocardial infarction within the past 6 months (New York Heart Association class III or IV heart disease)
• Any other serious medical condition that could compromise the patient's ability to adhere to treatment.
• Presence of any psychological, family, sociological or geographical condition that may hinder compliance with the study protocol and the follow-up program.
• In therapy with strong CYP3A inhibitors