Somebody asked over the weekend what I would do if someone failed alemtuzumab and had a persistent lymphopaenia. In short it depends on individual factors.
I have had three patients like this already.
#1: One patient had 5 courses of alemtuzumab and had developed anti-alemtuzumab antibodies and had very little depletion after her last round of treatment. Her disease remained active on MRI (multiple enhancing lesions). Her lymphocyte counts were around 0.9. I recommended rituximab, but as she was hoping to start a family she opted for de-escalation therapy and chose glatiramer acetate. Her neurologist tells me she is doing well on GA. This case illustrates that you don’t always have to go upwards in terms of efficacy, you can de-escalate and use a platform therapy after an IRT (immune reconstitution therapy).
#2: The second case failed alemtuzumab therapy at month 17 into her two years of treatment. Interestingly she repopulated rapidly after her second course, i.e. her lymphocyte counts were 0.8 at month 1 and were 0.9 the week before she started her second course of alemtuzumab. I suspect she may be another case of anti-alemtuzumab antibodies. She had previously failed glatiramer acetate. As she was JCV-seronegative she elected to be treated with natalizumab. This patient was offered HSCT, but turned it down when she realised there would be a good chance of her not being able to have children. The haematologist had given her 45-50% chance of going into the premature menopause. She had the option of egg banking, but as her MS active she was not prepared to wait 2 months and go through the relatively stressful, and invasive procedures, of ovarian stimulation and egg harvesting. Then there is the cost of storage.
#3: The third case who I saw last week with her second relapse after her second course of alemtuzumab (month 19). Interestingly, despite having just started natalizumab she still had a relapse. Her lymphocyte count was 0.8. when she started natalizumab. This last relapse came on just 2 weeks after her first infusion of natalizumab. This shows you that almost all DMTs take time to start working and that a relapse takes weeks to evolve. In other words, if you are destined to have a relapse in the next week or two natalizumab will not prevent it from occurring. This patient was also offered daclizumab, but after the recent death due to fulminant hepatotoxicity on daclizumab, she decided to go with natalizumab. Interestingly, this patient has also just developed Graves disease (thyrotoxicosis) so she was hit with a secondary autoimmune complication of alemtuzumab without deriving the long-term benefit of its efficacy. This particular patient would have chosen ocrelizumab, over natalizumab, if it was available. The option of rituximab is not on the table as in the first case as NHS England have stopped us using rituximab to treat MS.
I am hoping to create a ClinicSpeak App that deals with all the issues raised about the sequencing of treatments. The purpose of the App is to help people understand issues such as the ones raised in these case vignettes.