Two novel assays demonstrate persistent daratumumab exposure in a pediatric patient with delayed engraftment following allogeneic hematopoietic stem cell transplantation Journal Article
| Authors: | Major-Monfried, H.; Hosszu, K.; McAvoy, D. P.; Vallone, A.; Shukla, N.; Gillio, A.; Spitzer, B.; Kung, A. L.; Cancio, M.; Curran, K.; Scaradavou, A.; Oved, J. H.; O'Reilly, R. J.; Boelens, J. J.; Harris, A. C. |
| Article Title: | Two novel assays demonstrate persistent daratumumab exposure in a pediatric patient with delayed engraftment following allogeneic hematopoietic stem cell transplantation |
| Abstract: | Background aims: Daratumumab, a human IgG monoclonal antibody targeting CD38, is a promising treatment for pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL). We describe a case of delayed engraftment following a mismatched, unrelated donor hematopoietic stem cell transplant (HSCT) in a 14-year-old female with relapsed T-ALL, treated with daratumumab and chemotherapy. By Day 28 post-HSCT, the patient had no neutrophil engraftment but full donor myeloid chimerism. Methods: We developed two novel, semi-quantitative, antibody-based assays to measure the patient's bound and plasma daratumumab levels to determine if prolonged drug exposure may have contributed to her slow engraftment. Results: Daratumumab levels were significantly elevated more than 30 days after the patient's final infusion, and levels inversely correlated with her white blood cell counts. To clear daratumumab, the patient underwent several rounds of plasmapheresis and subsequently engrafted. Conclusions: This is the first report of both delayed daratumumab clearance and delayed stem cell engraftment following daratumumab treatment in a pediatric patient. Further investigation is needed to elucidate the optimal dosing of daratumumab for treatment of acute leukemias in pediatric populations as well as daratumumab's potential effects on hematopoietic stem cells and stem cell engraftment following allogenic HSCT. © 2024 |
| Keywords: | adolescent; cancer chemotherapy; clinical article; controlled study; human tissue; antibiotic agent; transplantation, homologous; prednisone; pathogenesis; case report; doxorubicin; methotrexate; drug megadose; flow cytometry; cd3 antigen; cd8 antigen; mucosa inflammation; cyclophosphamide; vincristine; plasmapheresis; stem cell transplantation; hematopoietic stem cell transplantation; drug effect; enzyme linked immunosorbent assay; acute lymphoblastic leukemia; monoclonal antibody; fever; chimera; maculopapular rash; cd16 antigen; antibodies, monoclonal; acute leukemia; disease severity; engraftment; whole body radiation; neutrophil; bone marrow biopsy; prophylaxis; cd11b antigen; cytotoxic t lymphocyte; therapy delay; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; methylprednisolone; immunoassay; pancytopenia; bacteremia; cd4 lymphocyte count; drug blood level; leukocyte count; graft rejection; graft survival; cd4 antigen; drug binding site; tacrolimus; bone marrow transplantation; leukemia relapse; granulocyte colony stimulating factor; adverse drug reaction; thymocyte; t lymphocyte subpopulation; t lymphocyte activation; cd19 antigen; cd14 antigen; allotransplantation; peripheral blood mononuclear cell; drug exposure; correlational study; abatacept; precursor t-cell lymphoblastic leukemia-lymphoma; natural killer t cell; hla system; patient transport; antibody-based immunotherapy; hypersensitivity; typhlitis; engraftment syndrome; respiratory distress; cd56 antigen; meropenem; procedures; asparaginase macrogol; absolute lymphocyte count; escherichia coli infection; humans; human; female; article; pseudomonas infection; t cell acute lymphoblastic leukemia; absolute neutrophil count; daratumumab; adp ribosyl cyclase/cyclic adp ribose hydrolase 1; receptor type tyrosine protein phosphatase c; pediatric patient; mismatched unrelated donor; cd8 lymphocyte count; novel treatments; electrochemiluminescent immunoassay; generalized maculopapular rash; natural killer cell count; prolonged pancytopenia |
| Journal Title: | Cytotherapy |
| Volume: | 26 |
| Issue: | 5 |
| ISSN: | 1465-3249 |
| Publisher: | Elsevier Science Ltd. |
| Date Published: | 2024-05-01 |
| Start Page: | 466 |
| End Page: | 471 |
| Language: | English |
| DOI: | 10.1016/j.jcyt.2024.01.005 |
| PUBMED: | 38430078 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Hannah Major-Monfried -- Source: Scopus |
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