Daratumumab for donor-specific anti-HLA antibody desensitization in a case of HLA-mismatched allogeneic stem cell transplantation

Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant

“…Individualization of the treatment plan is necessary, depending upon the DSA titer and patient comorbidities. DSA desensitization with daratumumab has been described in solid‐organ transplant recipients and in an HLA‐mismatched HCT recipient 5,6,9,11 . Interestingly, after receiving daratumumab, patient 5 became negative for C1q‐fixing antibodies, which likely improved her prognosis 4 .…”

“…A combination of treatment modalities, as implemented in this cohort, is key to the successful desensitization of DSAs. There are three main DSA treatment strategies: (a) inhibiting antibody production by targeting B lymphocytes with rituximab (a monoclonal antibody against CD20) or targeting plasma cells with bortezomib (a proteasome inhibitor) or daratumumab (a monoclonal antibody against CD38); (b) antibody removal (via TPE or immunoadsorption); and (c) antibody neutralization (via IVIg, donor platelets, or donor buffy coat administration) 9,10 . For our patients, a course of rituximab with or without bortezomib or daratumumab, and followed by TPE and IVIg administration proved to be an efficient strategy encompassing all of these elements.…”

“…1,8 Although our cohort of patients was small, we highlight some platelets, or donor buffy coat administration). 9,10 For our patients, a course of rituximab with or without bortezomib or daratumumab, and followed by TPE and IVIg administration proved to be an efficient strategy encompassing all of these elements. For this cohort, the days from DSA treatment to transplant conditioning vary slightly, which was due to factors such as TPE scheduling, donor availability, B-cell number and response to rituximab, DSA MFI level, and overall clinical status of the patient.…”

“…DSA desensitization with daratumumab has been described in solid-organ transplant recipients and in an HLA-mismatched HCT recipient. 5,6,9,11 Interestingly, after receiving daratumumab, patient 5 became negative for C1q-fixing antibodies, which likely improved her prognosis. 4 Although frequent blood product transfusion may be unavoidable, an effort should be made to limit exposure by minimizing both the number and volume of blood products or by choosing platelet units that do not expand sensitization to prevent DSA development.…”

Isatuximab Monotherapy for Desensitization in Highly Sensitized Patients Awaiting Kidney Transplant

“…Few studies are ongoing, and few clinical case reports are available regarding the use of anti-CD38 antibodies, which have demonstrated various levels of DSA reduction, for desensitization in patients awaiting transplantation. [10][11][12][13][14] Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide and dexamethasone, and in combination with carfilzomib and dexamethasone, for the treatment of patients with relapsed/refractory multiple myeloma. 15 Isatuximab binding to CD38 triggers a number of Fc-dependent mechanisms-antibody-dependent cellular cytotoxicity, complement dependent cytotoxicity, and antibodydirected cellular phagocytosis-and direct apoptosis.…”