Characterization of progressive multifocal leukoencephalopathy (PML) in patients treated with rituximab, brentuximab and ibrutinib: A report from the Southern Oncology Network on Adverse Reactions (SONAR).

Abstract

133 Background: Since the advent of Rituximab (R) in 1997, cancer immunotherapy is increasingly used for management of lymphoproliferative disorders. Unexpected cases of PML have been reported in HIV-negative patients in 2005 receiving Rituximab ( R) and subsequently in 2012 and 2014, who received brentuximab vedotin ( B) or ibrutinib ( I), respectively. We sought to compare and contrast clinical characteristics and outcomes of PML in HIV-negative patients who were treated with R, B or I therapy. Methods: Retrospective analysis of the FDA adverse event reporting system (FAERS) and previously published data by our group with confirmed cases of PML associated with R (1997-2008), B and I therapy (2009-2015). Results: PML develops early during the therapy with B and I, compared to that of R group. Confirmation of the diagnosis of PML by MRI in conjunction with JC virus identification in the cerebrospinal fluid or brain biopsy using objective criteria was found only in 40-60% of the cases. Among confirmed cases of R, I, or B-associated PML, mortality was > 90%, usually occurring within weeks to months following diagnostic confirmation. Rare cases of survival were associated with return of immunologic function, including in one case development of an immune reconstitution syndrome. Conclusions: This is the first study that compared the clinical characteristics of PML in R, B and I. PML cases can occur early during the therapy using B and I, while usually occurs late with R. Additional research is needed to quantify the risk factors of PML and to know if this association is causal or incidental. Meanwhile, physicians and patients should be vigilant in detecting and reporting this rare AE to minimize future fatalities [Table: see text]