Here is My Question:
Can a 68 year old with relapse/remitting MS, with slowly advancing balance issues, who had been on Ocrevus, but has been recently treated for Stage 3 squamous cell lung cancer with cisplatin/chemo and radiation therapy use Imfinzi/durvalumab?
We know the many possible side effects for people without MS. And we realize it's all very new...
Durvalumab is a form of cancer immunotherapy called an "immune check point inhibitor". To understand how these therapies work will require a little explanation.
Certain proteins (i.e.,CTLA-4, PD-1) typically expressed on the surface of immune cells (for instance, T cells) interact with a complementary protein (i.e., B7, PDL-1) on another cell (for instance, an antigen presenting cells or tumor cells) to prevent the immune cell (usually a cytotoxic T cell) from attacking and destroying the target. This is one of the mechanisms animals use to regulate immune responses. This form of regulation is important to prevent autoimmunity or excessive immune responses, but also prevents the immune system from attacking cancers effectively.
There are many different types of immune check point inhibitors available to treat solid cancers. One thing they all have in common is that they have revolutionized the treatment of solid cancers that used to respond very little to treatment. CTLA-4 inhibitors provide a check on the initial immune activation step whereas, PD-1 and PDL-1 inhibitors prevent tumors and normal tissue from turning off immune responses directed against these tissues. durvalumab inhibits PDL-1 and has been shown to be effective against lung cancer, as noted in the question.
All check point inhibitor therapies are associated with a risk of autoimmune reactions but less commonly directed against the nervous system. The actual percentage of patients with reactions directed against the peripheral or central nervous system varies in the literature but is probably between less than 10 % of people treated. Those already carrying a diagnosis of immune mediated disease, such as multiple sclerosis, may be at increased risk for worsening of their condition when treated with these therapies, but the data is very thin. One study using an analysis from an administrative database (not the most ideal for understanding mechanisms or outcomes) reported that 30 % of MS patients who received an immune checkpoint inhibitor experienced at least transient worsening of symptoms, but we don't know the extent of worsening or the persistence of worsening in these cases. Interestingly, the authors did not report any cases in people with MS treated with durvalumab, but this may be due to the limited experience with this drug in MS patients.
Most immune mediated reactions to check point inhibitor therapy responds to temporary cessation of treatment and initiation of corticosteroid therapy. This would generally be the approach taken with any MS patient undergoing treatment. I would hypothesize that prior treatment with ocrelizumab may help protect against certain types of immune reactions with check point inhibitor therapy, but this is speculation on my part.
These are tough decisions to make during periods of stress. I wish we had more definitive information for you at this time. For these types of treatments your oncologist will benefit from an experienced MS specialist, so make sure your entire team is on board.
Good luck to you
Revere P (Rip) Kinkel, MDProfessor of Neurosciences
Director of the Multiple Sclerosis Program
University of California San Diego
#multiplesclerosis #MS #Durvalumab #Ocrevus
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