So far this is associated with the use of the generic cladribine, probably in cancer, rather than oral variant in MS. It says there have been three cases.
Lipomed who make the generic version have issued this warning.
- Dosing in hairy cell leukemia is 10mg for 5 days = 50mg
- Dosing in Non-Hodgkins lymphoma and chronic lymphocytic leukemia = 35mg monthly to a maximum of 6 cycles = 210mg
- Dosing in multiple sclerosis. Dose used at QMUL = 30mg and up to 30mg one month later depending on lymphopenia. The mavenclad equivalent dose is about (25mg + 25mg a month apart) 50mg
We can see the cases reported a few years ago
A case of PML was reported in someone (81 years old) with HCL who got pentostatin (a chemotherapeutic drug) 2 years later and 3 years later developed PML. Their T cell counts were extremely low at 67 and 28 cells/mm*3. Therefore severe lymphopenia seems to be a problem.
In another case (67 years old) reported 6 months after the last dose of cladribine had 160 CD4+ cells/mm3 and 360 CD8+ cells/mm3 but had been down to 100 lymphocytes cells/mm3).
The dosing schedule in use for oral cladribine aims to reduce the chances of severe lymphopenia <500 cells/mms (<200 CD4 T cells) = grade 3 lymphopenia, <200 cells/mm3 (<50cells/mm3) = grade 4 lymphopenia
In the warning it says “If PML is suspected, stop cladribine treatment immediately and ensure the patient receives specialist investigation”
However, as cladribine give long term depletion, if PML occurs it may be problematical.
At the heart of the use at QMUL, is careful monitoring to ensure that persistent lymphopenia does not occur.
If you are taking mavenclad monitoring occurs to ensure that lymphopenia is reduced.
However, persistent lymphopenia is going to be a problem for any treatment. But which cell type deals with PML the best…I guess CD8.
Will PML occur in MS after Cladribine?
This is quite possible, it has occurred with most MS drugs