Daratumumab as a therapeutic option for rituximab-recalcitrant pemphigus.
Maud Maho-Vaillant, Alexis Lefebvre, Marie-Laure Golinski et al.
✦ AI-curated · Sources linked
Case in brief
Two patients with life-threatening pemphigus refractory to rituximab and other therapies received daratumumab, an anti-CD38 antibody targeting plasma cells. Rituximab failure was associated with incomplete B-cell depletion and persistence of memory B cells and plasmablasts. Daratumumab was followed by rapid clinical improvement, depletion of CD38-positive plasma cells, and reduced antidesmoglein antibodies. One patient relapsed after daratumumab was stopped; subsequent rituximab was ineffective in the presence of antirituximab antibodies, but combined daratumumab and belimumab achieved sustained complete remission. In the other patient, remission was consolidated with additional rituximab. No treatment-related adverse events were observed.
What made this case unusual
The report links rituximab-refractory disease to persistent B-cell populations and describes relapse after daratumumab withdrawal, with antirituximab antibodies limiting retreatment; combined daratumumab and belimumab was then associated with sustained complete remission.
Diagnostic / clinical pearl
In refractory pemphigus, incomplete B-cell depletion with persistent memory B cells and plasmablasts may accompany rituximab failure; monitoring B-cell and antidesmoglein responses can help characterize treatment response.
Why it matters
These cases suggest plasma-cell targeting with daratumumab, alone or alongside B-cell-targeting agents, may be an option in severe pemphigus that has not responded to rituximab and other therapies.