A recent study published in Authorea suggests that combination therapy of rituximab and daratumumab might be a promising therapeutic option for refractory post-transplant immune-mediated cytopenias (IMCs) including immune thrombocytopenic purpura (ITP).
The researchers presented a case study of a 17-year-old boy with adrenoleukodystrophy who underwent a bone marrow transplant from an unrelated donor using a reduced-intensity conditioning regimen. The transplant was successful, and the patient showed no signs of graft-versus-host disease (GVHD). However, on day 118 after the transplant, he was readmitted to the hospital due to oral bleeding and skin discoloration and was diagnosed with ITP.
Despite various treatment attempts, including intravenous immunoglobulin, corticosteroids, and thrombopoietin receptor agonists, the patient’s thrombocytopenia did not improve. He received daratumumab on day 191, which temporarily increased his platelet counts, but they later declined. Subsequently, he underwent multiple courses of rituximab in combination with prednisolone and romiplostim, leading to a gradual increase in platelet counts.
According to the study findings, the CD38-targeting therapy with daratumumab rapidly improved the first episode of rituximab-refractory ITP, indicating the presence of autoreactive plasma cells. In comparison, the additional rituximab therapy was found effective in counteracting daratumumab-refractory ITP recurrence, suggesting the presence of remnant autoreactive B cells.
“Thus, sequential or combination therapy with rituximab and daratumumab appears to be a promising therapeutic option for refractory post-transplant IMCs, which might be caused by multiple antibody-secreting cell populations,” the authors commented.
Read more about ITP therapies
IMCs, including ITP, autoimmune neutropenia, and autoimmune hemolytic anemia, have been recently identified as significant complications after allogeneic hematopoietic cell transplantation (HCT), with a cumulative occurrence of 2.1% to 52.6%. Several risk factors, including younger recipient age at HCT, nonmalignant underlying disease, cord blood transplantation, an unrelated donor, and a reduced-intensity conditioning regimen, have been highlighted for developing IMCs following transplantation.
ITP is a rare autoimmune disorder characterized by an abnormally low number of blood platelets (<100,000/µL) manifesting as a bleeding disorder with symptoms including easy bruising, bleeding gums, and internal bleeding. The underlying mechanisms of ITP post-HCT remain poorly understood. It has been speculated that the immune dysregulation resulting from conditioning regimens, infections, GVHD, immunosuppressive medications, deficient and dysfunctional regulatory T cells, and/or HLA-mismatched donor-derived naive T cells contribute to the development of IMCs following HCT, primarily through the production of autoantibodies targeting hematopoietic cells.
Recent high-throughput single-cell bioassay studies on patients with ITP have revealed the presence and spread of autoreactive plasma cells in various hematopoietic organs such as the spleen, bone marrow, and lymph nodes, suggesting that the efficacy of B cell depletion using rituximab may be reduced in these cases. Rituximab, an anti-CD20 monoclonal antibody (mAb), daratumumab, an anti-CD38 mAb, mycophenolate mofetil, and bortezomib have been used as second-line therapies for refractory or recurrent cases.
Reference
Umeda K, Shino Y, Uchihara Y, et al. Successful sequential therapy with rituximab and daratumumab for refractory post-transplant immune thrombocytopenic purpura. Authorea. Published online April 28, 2023. doi:10.22541/au.168268210.03204731/v1
