Post

1) The pilot results (n = 10) for the Daratumumab trial on ME/CFS have been published and they look quite encouraging. Tolerability and feasibility were good and some patients had substantial improvements.

2) This comes from the Norwegian team that conducted the Rituximab trials. Both are monoclonal antibodies that target markers on the surface of certain cells. Rituximab targets CD20 which is mainly found on B cells, while Daratumumab targets CD38 found on plasma cells.

3) The authors speculate that after an infection, long-lived plasma cells are producing antibodies in ME/CFS. Since these plasma cells are CD20 negative, they are not affected by (short-term) Ritxumab treatment. Hence the idea to try Daratumumab which does target these cells.

4) Four patients had no significant clinical changes, but the improvements in the other patients were quite big. SF-36 physical functioning, for example, increased from 25.9 to 55 (+29), which is bigger than for example GET/CBT in the PACE trial (+18).

5) It's also interesting that improvements are not evenly spread across all participants. Some had no improvement at all, while others were almost back to normal. 5/10 patients had sustained improvement for 12-24 months and had a mean step count above 10,000/24 h for some weeks.

6) Also interesting: NK cells were quite low in all participants but in those where it was slightly higher, the treatment response was better. The authors speculate that a higher number of baseline NK cells enhanced plasma-cell depletion.

7) They are testing a lower dose of Daratumumab in 4 patients with ME/CFS following Sars-Cov-2 who had NK-cells numbers above 125 (x10^6/L). This case series will be published later.

8) Caveat: because daratumumab reduces antibodies (IgG reduced IgG by 50%), it could make patients more susceptible to infections. In this small pilot trial, most participants had one or two episodes of a viral upper airway infection but there were no serious adverse reactions.

9) Another caveat is that the treatment response was equally big in the 2015 Rituximab trial where physical functioning (Sf-36) increased from 40 to 68 (+28) The later randomised trial however showed no significant effect, which may also be the case here.

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