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CD38: A target in relapsed/refractory acute lymphoblastic leukemia-Limitations in treatment and diagnostics

B. Vakrmanová, M. Nováková, P. Říha, M. Žaliová, E. Froňková, E. Mejstříková, J. Starý, O. Hrušák, L. Šrámková

. 2022 ; 69 (9) : e29779. [pub] 20220520

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Daratumumab, an anti-CD38 antibody, is used experimentally in the treatment of relapsed acute lymphoblastic leukemia (ALL). We treated five patients suffering from relapsed ALL with daratumumab. Four patients had T ALL, three of whom achieved complete remission (CR) after treatment and underwent stem cell transplant (SCT). Two of them had a second relapse and died 6 and 8 months after SCT, respectively. One transplanted T ALL patient remained in CR2 15 months after relapse. In the remaining T-ALL patient, the disease progressed under daratumumab treatment, and the patient died early after the first relapse. The B-cell precursor ALL patient with a second CD19-negative relapse, whose disease turned out to be resistant to the combination of daratumumab with chemotherapy, later achieved CR3 with inotuzumab ozogamicin, underwent SCT and remained in CR3. Leukemia burden should be monitored after daratumumab, and care should be taken not to misclassify leukemic cells with false negativity of surface CD38; using an antibody reacting with nondaratumumab epitopes is advantageous.

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$a Daratumumab, an anti-CD38 antibody, is used experimentally in the treatment of relapsed acute lymphoblastic leukemia (ALL). We treated five patients suffering from relapsed ALL with daratumumab. Four patients had T ALL, three of whom achieved complete remission (CR) after treatment and underwent stem cell transplant (SCT). Two of them had a second relapse and died 6 and 8 months after SCT, respectively. One transplanted T ALL patient remained in CR2 15 months after relapse. In the remaining T-ALL patient, the disease progressed under daratumumab treatment, and the patient died early after the first relapse. The B-cell precursor ALL patient with a second CD19-negative relapse, whose disease turned out to be resistant to the combination of daratumumab with chemotherapy, later achieved CR3 with inotuzumab ozogamicin, underwent SCT and remained in CR3. Leukemia burden should be monitored after daratumumab, and care should be taken not to misclassify leukemic cells with false negativity of surface CD38; using an antibody reacting with nondaratumumab epitopes is advantageous.
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$a Nováková, Michaela $u Department of Pediatric Hematology and Oncology, Charles University Second Faculty of Medicine, CLIP, Prague, Czech Republic $u Department of Pediatric Hematology and Oncology, Motol University Hospital, Prague, Czech Republic
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$a Říha, Petr $u Department of Pediatric Hematology and Oncology, Motol University Hospital, Prague, Czech Republic
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$a Žaliová, Markéta $u Department of Pediatric Hematology and Oncology, Charles University Second Faculty of Medicine, CLIP, Prague, Czech Republic
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$a Starý, Jan $u Department of Pediatric Hematology and Oncology, Motol University Hospital, Prague, Czech Republic
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