risk of PML associated with rituxan

[Guest guest]

The incidence of PML in NHL is unknown; the 57 cases were reported over a

long period of time from 12 centers and other sources ... thus the incidence

is *very* low. Apologies for not providing the background information

along with the remark about the number of cases! ~ Karl

==

Progressive multifocal leukoencephalopathy (PML) after rituximab therapy in

HIV-negative patients:

a report of 57 cases from the Research on Adverse Drug Events and Reports

project

http://1.usa.gov/u3Hhbc

[The 57 ] " Cases were identified among rituximab-treated patients by

clinicians from 12 cancer centers or academic hospitals (22 cases) or by

reviewing FDA reports (11 cases), the manufacturer's database (30 cases),

and publications (18 cases; MeSH search terms: leukoencephalopathy,

rituximab, immunosuppressed, lymphoma, and leukemia).18-31

The search covered the period from 1997, the date of the first FDA approval

granted for rituximab, to December 31, 2008. Duplicate reports were

identified based on age, sex, and underlying illness. Inclusion criteria

were receipt of rituximab therapy before PML diagnosis or symptoms; PML

confirmation based on histologic examination of brain tissue

(histology-confirmed) or magnetic resonance imaging showing lesions

consistent with a demyelinating process and documentation of cerebrospinal

fluid (CSF) JCV DNA by polymerase chain reaction (PCR;

laboratory-confirmed); and no evidence of HIV infection.32

copying from the Discussion: " Some study limitations should be noted.

Epidemiologic estimates of PML incidence are difficult to derive.

In the general population, PML is estimated to occur at 1 case per 200000

persons.67 Among HIV-infected populations, incidence rates decreased from

3.3 cases per 1000 person-years at risk in 1995 to 1996 to 1.3 cases per

1000 person-years at risk in 2000 to 2006, after the introduction of highly

active antiretroviral therapy.46 Among persons with multiple sclerosis or

Crohn disease, the estimated incidence of natalizumab-associated PML is 1

PML case per 1000 natalizumab-treated patients.52

For PML-associated with rituximab, Kavanaugh and Matteson reported 2 PML

cases per 8000 rituximab-treated SLE patients.68

It is not possible to accurately estimate the incidence of

rituximab-associated PML among persons with hematologic malignancies because

of incomplete reporting of PML cases among rituximab-treated patients and

incomplete data on the number of unique patients with lymphoid malignancies

who have received rituximab.

It should also be noted that the epidemiology of PML in the setting of

lymphoid malignancies has changed over time. Before 1990, most PML cases

occurred among persons with Hodgkin disease, whereas in recent years, with

the development of purine analogs, hematopoietic stem cell transplantation

procedures, and rituximab, most PML cases occur among non-HIV-infected

persons with NHL or chronic lymphocytic leukemia.50

Consideration should be given to conducting epidemiologic studies to

prospectively evaluate incidence rates and risk factors for PML among

cohorts of rituximab-treated patients with NHL, autoimmune diseases, SLE,

rheumatoid arthritis, and multiple sclerosis.

Finally, causation assessment is more difficult when PML occurs among

rituximab- versus natalizumab-treated persons because PML occurs in the

absence of rituximab therapy among persons with NHL or autoimmune diseases,

whereas it has not been reported in the absence of natalizumab therapy among

persons with multiple sclerosis or Crohn disease.

In conclusion, rituximab administration may increase risks of developing

PML, although the absolute risk of developing PML is probably low.

As use of rituximab expands to diverse clinical settings, clinicians and

patients should be aware of the potential for PML after rituximab therapy.

Awareness and reporting of rituximab-associated PML cases to the FDA are

essential to improve our understanding of risk factors, natural course, and

alternative therapeutic approaches. Despite widespread public health

advisories describing 2 patients with SLE and 1 patient with rheumatoid

arthritis who were diagnosed with rituximab-associated PML, we identified 22

previously unreported cases associated with lymphoid malignancies and

immunologically mediated cytopenias.

Early diagnosis of PML will prompt efforts at immune reconstitution, which

may be beneficial in improving survival rates. Finally, early diagnosis

before irreversible neurologic damage has occurred will be crucial for

evaluation of the efficacy of new antiviral treatments.

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