From the Guidelines
Progressive multifocal leukoencephalopathy (PML) is a rare but serious complication that can occur after treatment for follicular lymphoma, and immediate discontinuation of immunosuppressive therapy is crucial if PML is suspected. When considering the treatment of follicular lymphoma, particularly with regimens like Fludarabine/Cyclophosphamide/Rituximab (FCR) as mentioned in the NCCN clinical practice guidelines in oncology 1, it's essential to weigh the benefits against the risks, including the potential for PML. The FCR regimen has shown significant efficacy in treating Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, with an overall response rate (ORR) of 80% and 32.5% of patients achieving at least a very good partial response (VGPR) 1. However, the use of such immunosuppressive therapies increases the risk of opportunistic infections, including PML. Key considerations in managing PML include:
- Immediate discontinuation of immunosuppressive therapy
- Confirmation of diagnosis through MRI brain imaging and CSF testing for JC virus DNA
- Immune reconstitution as the primary approach to treatment
- Potential use of mirtazapine or mefloquine, though evidence is limited and neither is proven effective
- Consideration of corticosteroids if immune reconstitution inflammatory syndrome (IRIS) develops Given the poor prognosis of PML, with mortality rates of 30-50% and significant neurological sequelae in survivors, close neurological monitoring of patients receiving rituximab or other immunosuppressive therapies for follicular lymphoma is strongly recommended, with prompt evaluation of any new neurological symptoms. The risk of PJP (Pneumocystis jirovecii pneumonia) associated with FCR treatment, as noted in the guidelines 1, further underscores the need for prophylactic measures and vigilant monitoring for opportunistic infections in patients undergoing immunosuppressive therapy for follicular lymphoma.
From the FDA Drug Label
Progressive Multifocal Leukoencephalopathy (PML). PML is a rare, serious brain infection caused by a virus that can happen in people who receive RITUXAN. People with weakened immune systems can get PML PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML Tell your healthcare provider right away if you or your child have any new or worsening symptoms or if anyone close to you notices these symptoms: confusion dizziness or loss of balance difficulty walking or talking decreased strength or weakness on one side of your body vision problems
Rituximab treatment is associated with a risk of Progressive Multifocal Leukoencephalopathy (PML), a rare and serious brain infection. Patients with weakened immune systems, such as those with follicular lymphoma, are at increased risk of developing PML.
- Key symptoms of PML include:
- Confusion
- Dizziness or loss of balance
- Difficulty walking or talking
- Decreased strength or weakness on one side of the body
- Vision problems It is essential to monitor patients for these symptoms and report any new or worsening symptoms to their healthcare provider immediately 2.
From the Research
Progressive Multifocal Leucoencephalopathy (PML) Post Follicular Lymphoma Treatment
- PML is a rare and often fatal demyelinating disease of the central nervous system caused by the John Cunningham virus (JCV) 3, 4, 5, 6.
- It can occur in patients with follicular lymphoma, particularly those who have undergone immunosuppressive treatments such as hematopoietic stem cell transplantation, rituximab-bendamustine therapy, or epcoritamab therapy 3, 4.
- Symptoms of PML in patients with follicular lymphoma can include progressive weakness, postural instability, dysarthria, visual disturbances, ataxia, and cognitive impairment 3, 4, 5, 6.
- Diagnosis of PML can be made through magnetic resonance imaging (MRI) scans, which show bilateral hyperintense lesions in the cerebellum and centrum semiovale, and through detection of JCV DNA in cerebrospinal fluid (CSF) or peripheral blood by polymerase chain reaction (PCR) assay 3, 4, 6.
- Treatment options for PML are limited, and the disease often has a fatal outcome, with patients typically dying within a few months of diagnosis 3, 4, 6.
- The use of biologics, such as rituximab and epcoritamab, in the treatment of follicular lymphoma may increase the risk of developing PML, highlighting the need for careful monitoring and screening of patients for JCV viremia prior to treatment 4, 5.
- Advances in the understanding of follicular lymphoma and the development of novel therapies, including targeted therapeutics and immunotherapeutic strategies, may improve outcomes for patients with this disease, but the risk of PML remains a concern 7.