Scientists report 4th case of daratumumab controlling CAD
Treatment is a B-cell depleting therapy approved for multiple myeloma
Daratumumab, which is approved to treat some cancers, was effective at controlling cold agglutinin disease (CAD) in an elderly woman who failed to respond to rituximab, a study reports.
The report, “Refractory cold agglutinin disease successfully treated with daratumumab. A case report and review of literature,” is likely the fourth documented case where daratumumab was able to control hard-to- treat CAD. It was published in Hematology.
CAD is an autoimmune disease caused by the production of self-reactive antibodies that bind to red blood cells at low temperatures, leading to their destruction. Low levels of red blood cells affect oxygen transport throughout the body and lead to symptoms such as weakness and fatigue.
Antibodies are produced by immune B-cells, particularly plasma cells, their more mature form, so depleting antibody-producing cells may be a viable strategy for CAD.
Rituximab is a B-cell-depleting therapy developed for blood cancers, but it’s commonly used off-label as a first-line therapy in CAD. Sold as Rituxan in the U.S. and MabThera in Europe, and with generics available, it works by targeting the CD20 protein.
CD20 is found at high levels on the surface of B-cells across their several stages of maturation, but at lower levels on plasma cells, which produce the largest number of antibodies. Rituximab’s inability to affect long-lived plasma cells may explain why not all patients respond to it.
Daratumumab as treatment for CAD
Daratumumab, sold under the brand name Darzalex, is a B-cell depleting therapy approved for multiple myeloma, a cancer marked by the out-of-control growth of plasma cells. It specifically targets CD38, a protein highly present at the surface of B-cell precursors and plasma cells.
Based on its mechanism of action, daratumumab has been tested in some people with hard-to-treat CAD. To date, it’s been effective at controlling CAD in three men who’d failed to respond to rituximab — one in the U.K., one in Italy, and one in the U.S.
Scientists in Qatar described the case of 69-year-old woman with CAD who didn’t respond to rituximab, but was successfully treated with daratumumab.
The woman was evaluated at the researchers’ clinic due to severe anemia, or very low levels of hemoglobin, the protein in red blood cells that transports oxygen throughout the body. She also reported shortness of breath, dizziness, and fatigue in the preceding months.
Blood work showed high levels of markers of red blood cell destruction (hemolysis) and a blood sample analysis revealed red blood cell clumping, a sign of CAD. She also tested positive on a direct Coombs test that detects antibodies attached to red blood cells, confirming a CAD diagnosis.
The woman received two units of a blood transfusion and was advised to avoid exposure to cold. A few weeks later, however, her symptoms persisted and she showed a drop in hemoglobin levels and required another blood transfusion.
She was started on rituximab, but remained severely anemic after several months of treatment and required regular blood transfusions to keep her red blood cell counts stable.
Due to her poor treatment response, the woman was switched to daratumumab, which was administered according to the same dosing schedule that’s used for multiple myeloma — 16 mg/kg every week for eight weeks, then every other week for eight weeks and monthly thereafter.
She received 18 cycles of daratumumab over six months. She also was treated weekly with erythropoietin, a hormone that helps stimulate the growth of new red blood cells.
During the first two months on daratumumab, the woman required one blood transfusion, but after that, she didn’t need any more and her red blood cell levels normalized. Her symptoms resolved and levels of hemolysis markers were markedly reduced.
The woman continues to take monthly daratumumaband will do so for about a year.
The researchers concluded daratumumab was effective in this case and didn’t cause notable safety issues. The woman reported some mild fatigue after the first few treatment cycles, but no other side effects.
Data from this and previous reports suggest daratumumab “may be effective; however, it may take weeks to months to show a result,” wrote the researchers, who called for more large-scale studies to evaluate its utility in CAD.