What happens in the long-term after alemtuzumab. The simple answer is that we do not know?
Based on the long-term Cambridge data there are a few people that have converted to SPMS, and according to ProfC from Cambridge these people tended to be those who started DMT later in their disease course and those that showed less responsive to treatment.
CAMPATH-1H was tried in a miriad of conditions before the two Cs from Cambridge tried it in MS.
In this report, the study looks at the bloods 20 years after alemtuzumab and it is clear that the cells numbers in the bloods do not revert back to normal. The immune output of cells relates to bone marrow and thymic output and with age these drop. Compared with controls the alemtuzumab cohort had significantly reduced CD4+ and CD8+ central memory T-cells, CD5+ B cells, naïve B cells and CD19+CD24hiCD38hi transitional (putative regulatory) B cells.
Compilation of the primary causes of death from the entire cohort from 1994 to 2015 showed overall 37 of the original 53 patients who received alemtuzumab had died. The predominant causes of death were cardiovascular/atherosclerotic (n = 12), infection (n = 11), and malignancy (n = 8). Other causes were non-malignant gastrointestinal tract perforation (n = 2), pulmonary fibrosis (n = 1), dementia (n = 1), upper gastrointestinal bleed (n = 1) and primary sclerosing cholangitis (n = 1).
It is evident that once you have alemtuzumab your white cell profile changes for ever. This in part because as you age your thymus where T cells are educated, atrophies. So once you deplete after this the immune machinery is not working the same as it was before. In the animals too, after imune depletion the cell levels dont return in the same way. However this is also part of the re-booting process, that helps alemtuzumab switch off MS
Immune reconstitution 20 years after treatment with alemtuzumab in a rheumatoid arthritis cohort: implications for lymphocyte depleting therapies.
Cooles FA, Anderson AE, Drayton T, Harry RA, Diboll J, Munro L, Thalayasingham N, Östör AJ, Isaacs JD. Arthritis Res Ther. 2016 0;18(1):302
BACKGROUND:Alemtuzumab, an anti-CD52 monoclonal antibody, was administered to patients with RA between 1991 and 1994. We have followed a cohort of recipients since that time and previously reported significant delays in immune reconstitution. Here we report >20 years of follow-up data from this unique cohort.
METHOD:Surviving alemtuzumab recipients were age, sex and disease duration matched with RA controls. Updated mortality and morbidity data were collected for alemtuzumab recipients. For both groups antigenic responses were assessed following influenza, Pneumovax II and combined diphtheria/tetanus/poliovirus vaccines. Circulating cytokines and lymphocyte subsets were also quantified.
RESULTS:Of 16 surviving alemtuzumab recipients, 13 were recruited: 9 recipients underwent a full clinical assessment and 4 had case notes review only. Since our last review 10 patients had died from causes of death consistent with long-standing RA, and no suggestion of compromised immune function. Compared with controls the alemtuzumab cohort had significantly reduced CD4+ and CD8+ central memory T-cells, CD5+ B cells, naïve B cells and CD19+CD24hiCD38hi transitional (putative regulatory) B cells. Nonetheless vaccine responses were comparable between groups. There were significantly higher serum IL-15 and IFN-γ levels in the alemtuzumab cohort. IL-15 levels were inversely associated wth CD4+ total memory and central memory T cells.
CONCLUSION: After 20 years the immune system of alemtuzumab recipients continues to show differences from disease controls. Nonetheless mortality and morbidity data, alongside vaccination responses, do not suggest clinical immune compromise. As lymphodepleting therapies, including alemtuzumab, continue to be administered this work is important with regard to long-term immune monitoring and stages of immune recovery.