Failure of mobilization of hematopoietic stem cells associated with elevated serum levels of anti‐CD38 monoclonal antibody

Abstract

Daratumumab is an anti-CD38 antibody that is increasingly incorporated in induction regimens for treating patients with newly diagnosed multiple myeloma (NDMM).Previous reports have demonstrated a lower yield of hematopoietic stem cells (HSCs) after induction with daratumumab; however, none of them reported a failure to collect an adequate number of HSCs. We describe a case of adequate HSC mobilization failure in a patient who inadvertently received excessive doses of daratumumab and was confirmed by higher-than-expected circulating levels of daratumumab by mass spectrometry. Eventual clearance of circulating daratumumab was associated with the successful mobilization and harvesting of HSCs.

Predictive factors for peripheral blood stem cell mobilization in multiple myeloma in the era of novel therapies: A single‐center experience

“…A report indicated that elevated serum levels of anti-CD38 monoclonal antibody may affect mobilization by binding to low levels of CD38 antigen expression of CD34 + cells. 2 Predicting mobilization failure before it starts may enable patients to develop tailored strategies, such as omitting CTX in induction, monitor closely and use early plerixafor in case of low PB CD34 + cells count. It has been suggested that the negative effect of lenalidomide on mobilization can be overcome by chemo-mobilization.…”

“…As novel drugs, such as daratumumab, pomalidomide, and carfilzomib, are increasingly incorporated into the first‐line induction therapies for MM, 2,3 traditional risk factors for PM are different. CASSEIOPIA, GRIFFIN, and several other phase 3 studies have supported that the daratumumab‐based triplet or quadruplet regimen as the first‐line therapy in induction 12,13,36,37 .…”

“…However, we know little about the molecular mechanisms by which daratumumab affects mobilization. A report indicated that elevated serum levels of anti‐CD38 monoclonal antibody may affect mobilization by binding to low levels of CD38 antigen expression of CD34 + cells 2 …”

“…Daratumumab‐based triplets or quadruplets are rapidly becoming the standard therapy in induction for MM 2,11 . However, concerns have arisen that daratumumab may be disadvantageous for PBSC mobilization.…”

“…Multiple myeloma (MM) is a malignant plasmacyte disease that tends to occur in the elderly 1 . During the past few years, novel agents such as daratumumab, pomalidomide, and carfilzomib have increasingly been incorporated in first‐line induction therapies for MM 2,3 . Autologous hematopoietic stem cell transplantation (auto‐HCT) is also part of standard frontline therapy for most MM patients 4,5 .…”