Children with B-cell or T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) in whom the disease recurs (relapse) may develop resistance and more often respond inadequately to existing drugs. An allogeneic stem cell transplant then represents the only chance for a cure, but to do so the disease must first be reduced. Therefore, new therapies are needed.
Daratumumab is a monoclonal antibody (it is a form of immunotherapy): this is a protein that recognizes and binds to another unique protein, in this case CD38 on the surface of the tumor cell. CD38 is present in high amounts on the surface of tumor cells in ALL and LL. The binding of daratumumab to CD38 allows the immune system to recognize and destroy the tumor cell. Daratumumab is already being used in adults with multiple myeloma, another form of blood cancer.
In this study, children received daratumumab in combination with standard chemotherapy. Daratumumab could be safely added to chemotherapy. Most participants experienced side effects from daratumumab, but these were similar to what had previously been seen in adults.
Enabling stem cell transplantation
Between 2018 and 2022, 24 children with relapsed T-cell ALL received daratumumab in combination with chemotherapy. In 41.7% of these children, all signs of the disease had disappeared after the first course of treatment (complete response). Overall, 83.3% of this group of children showed a complete or near-complete response. Three quarters of these children were subsequently able to receive an allogeneic stem cell transplant.
Daratumumab also induced a complete response in a proportion of children with relapsed LL and contributed to making a stem cell transplant possible.
In children with recurrent B-cell ALL, daratumumab had less effect. Seven children with B-cell ALL received daratumumab; none of them showed a complete response after the first course. Therefore, this group was not expanded further.
In summary, the results of this study indicate that daratumumab can be safely combined with standard chemotherapy in children with relapsed B-cell ALL and T-cell ALL or LL, including those who are heavily pretreated. Addition of daratumumab to standard chemotherapy helped make allogeneic stem cell transplantation possible. The researchers believe it is worthwhile to further investigate the clinical activity of daratumumab in children with T-cell ALL, both in the relapsed and newly diagnosed setting. A study with a similar drug, isatuximab, has also been completed and results are awaited.
The scientific publication can be found here: Bhatla T, Hogan L MD, Teachey DT, et al. Daratumumab in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma: DELPHINUS Study. Blood. 2024 Aug 16:blood.2024024493.