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

Abstract

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.

Daratumumab‐induced minimal residual disease negative remission in CD38 (dim)‐positive pediatric acute myeloid leukemia

“…6 Previous reports on daratumumab in acute lymphoblastic leukemia have used a dose of 16 mg/kg, which is typical of myeloma protocols. 7 MRD-negative remission induction is fast as happened with this child who attained MRD-negative remission after 4 weekly doses. This remission was sustained for 10 weeks, which provides a very good window to proceed with HSCT as curative therapy.…”

Daratumumab induced Minimal Residual Disease Negative Remission in CD 38 (dim) Positive Pediatric Acute Myeloid Leukemia

“…6 Previous reports on daratumumab in acute lymphoblastic leukemia have used a dose of 16 mg/kg which is typical myeloma protocol. 7 MRD negative remission induction is fast as happened with this child who attained MRD negative remission after 4 weekly doses. This remission was sustained for 10 weeks which provides a very good window to proceed with HSCT as curative therapy.…”

The role of daratumumab in relapsed/refractory CD38 positive acute leukemias—case report on three cases with a literature review

“…Four patients had T-ALL, one had B-ALL, and all patients were treated with daratumumab combined with or without chemotherapy. The number of daratumumab infusions was between 3 and 21, and 3 of 5 patients achieved CR ( 28 ). In addition, there is one case report of a patient who was resistant to standard chemotherapy and who was treated with salvage chemotherapy containing nelarabine, etoposide, and cyclophosphamide.…”