PB1328 - The therapeutic efficacy of daratumumab in the management of multiply relapsed refractory immune thrombotic thrombocytopenic purpura: an Australian single centre experience.

Background: Relapsed refractory immune thrombotic thrombocytopenic purpura (iTTP) is a rare and heterogeneous condition associated with high rates of morbidity and mortality. There is no universal consensus on sequential lines of therapy for multiply relapsed iTTP, especially following anti-CD20 monoclonal antibodies (rituximab), chemotherapy, splenectomy and inability to access anti-von Willebrand factor (vWF) directed therapy (caplacizumab). Several case series have highlighted the promising efficacy of plasma-cell directed therapies such as a proteasome inhibitor (bortezomib) and anti-CD38 monoclonal antibody (daratumumab) in the absence of high quality randomised clinical trial data.

Aims: Evaluate the real-world role of daratumumab as salvage treatment for difficult-to-treat iTTP via illustration of the clinical courses of two patients at our institution over the past 12 months.
Provide practical insight into the vagaries of monitoring and managing persistent subnormal levels of a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13 (ADAMTS-13) in iTTP and clinical complexity of determining the next therapeutic option.

Methods: The case vignettes of both patients will include details of clinical presentation, relevant investigations, treatment history, response assessments based on updated criteria from the International Working Group (IWG) for TTP and current progress at time of writing. Therapeutic response to daratumumab for each patient will be depicted in graphical form to demonstrate changes in ADAMTS-13 activity levels with treatment.

Results: Treatment response varied significantly between both patients. Patient A demonstrated a steady decline in ADAMTS-13 activity level before demonstrating a late rise at week 7. Patient B demonstrated no increase in ADAMTS-13 activity level after 2 doses of daratumumab but demonstrated a relatively significant increase (>10%) following 4 doses, given low pre-treatment level (1.6%).

Conclusion(s): Daratumumab may be a viable treatment option in a subset of patients with relapsed refractory iTTP. However, further studies are required to elucidate the optimal utility of this agent as salvage therapy.