Real World Data on Ibrutinib Use in PCNSL Rel/Ref

Overview

PCNSL is a rare and aggressive subtype of B lymphoma that has been recognized as a distinct disease entity in the latest edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissue and is defined as DLBCL that develops exclusively in the brain parenchyma, spinal cord, leptomeninges and eye. In patients under 70 years of age without severe comorbidities, first-line treatment with induction chemo-immunotherapy according to the MATRix scheme (Methotrexate, Cytarabine, Tiothepa, Rituximab) and subsequent consolidation with HDCT followed by ASCT achieved the best results in terms of PFS and OS. Data on patients enrolled in a randomized phase 2 study showed an OS of 70% at a median FU of 88 months. In patients\> 70 years of age or with low KPS, the prognosis remains significantly lower in the younger population. Several population studies have shown a stable increase over the past 30 years in terms of PFS and OS in patients aged under 70 years, while in patients over 70 years or with KPS \<70%, the survival curves are not satisfactory. in part because these patients are often referred to BSC alone, despite the benefit in PFS and OS demonstrated with HD-MTX-based treatments (≥1 g / m2) combined with oral alkylating agents or cytarabine in high doses.

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.