Daratumumab injection therapy for cancer may help in hard-to-treat ITP

Daratumumab, an injection therapy approved to treat myeloma, may help to control immune thrombocytopenia (ITP) in individuals whose disease doesn’t respond well to available treatments.

That’s according to new data from a Phase 2 clinical trial that tested the cancer therapy, sold under the brand name Darzalex, in a small group of people with hard-to-treat ITP, some of whom had undergone more than four previous treatments.

“This Phase 2 study demonstrates the safety and efficacy of … daratumumab in heavily-pretreated ITP patients,” the researchers wrote, noting that the injection therapy “demonstrated short- and long-term efficacy” among participants.

Still, the team noted that a “prospective, controlled trial is essential to confirm the findings in our study, optimize treatment strategies, and assess the role of re-treatment in relapsed responders.”

Titled “Safety and efficacy of daratumumab in immune thrombocytopenia,” the study was published in the journal Blood Advances by a team of researchers in Europe.

Cancer injection therapy daratumumab tested in 21 ITP patients

ITP is an autoimmune disease in which immune cells make antibodies that attack platelets, the cell fragments that help blood to clot. These attacks cause platelet counts to drop and impair blood clotting, ultimately leading to symptoms like excessive bleeding.

A range of ITP treatments is available, but they don’t work for everyone. In people who fail to respond to available treatments, it’s thought the disease may be driven by antibody-producing immune cells called plasma cells.

Daratumumab is a medication that works to kill plasma cells by targeting a protein on their surface known as CD38. It’s sold by Johnson & Johnson as Darzalex as an approved treatment for multiple myeloma, a type of blood cancer marked by the uncontrolled growth of plasma cells. Because daratumumab kills plasma cells, and plasma cells are thought to drive ITP, some scientists have speculated that daratumumab may be useful in treating ITP.

To explore this idea, scientists conducted a Phase 2 clinical trial called DART (NCT04703621), which was carried out at six centers across three countries: Denmark, France, and Norway.

The study enrolled 21 people with ITP whose disease had not been adequately controlled with at least two available treatments; most participants had previously tried four or more ITP therapies.

The first three participants underwent a safety run-in where they received four weekly subcutaneous, or under-the-skin, injections of daratumumab. The remaining 18 participants received either eight weekly injections or eight weekly injections followed by two additional injections given every other week. The median duration of follow-up was slightly less than a year.

The main method used to evaluate the therapy’s effectiveness was to assess the number of patients who had sustained platelet levels of at least 50 billion platelets per liter of blood at least a month after the last daratumumab injection. Of the 21 participants, 10 met this goal. An 11th patient didn’t meet the response criteria at four weeks after the last dose, but did meet those criteria a few weeks later.

Sustained response to treatment seen for 8 trial participants

A sustained response — elevated platelet levels maintained for a few months after the last daratumumab injection — was documented in eight participants. The researchers noted that responses were seen in patients given all dosing regimens, with no regimen showing notably better effects, though the small size of the study makes it hard to draw meaningful comparisons.

Also of note, all patients who responded to daratumumab were able to stop taking other ITP therapies.

“This indicates that response to daratumumab is largely if not solely related to the drug and is independent of other medications,” the scientists wrote. “This effect, if confirmed, may translate into a big advantage to the patient and health care system.”

Patient-reported data indicated that measures of life quality tended to improve following treatment with daratumumab. Participants who met response criteria also tended to report an easing of fatigue following treatment.

[The study findings indicate] that response to daratumumab is largely if not solely related to the drug and is independent of other medications. … This effect, if confirmed, may translate into a big advantage to the patient and health care system.

Trial biomarker data indicated that daratumumab reduced antibody levels as expected, and safety data indicated the therapy was generally well tolerated. The most common treatment-related side effects were injection site reactions, infusion-related reactions, and diarrhea. One of these was severe, but all were resolved, and no other serious side effects were reported.

“Treatment with subcutaneous daratumumab was associated with mainly mild to moderate and transient adverse events … Infusion reactions were infrequent, manageable, and did not recur with subsequent daratumumab injections,” the researchers wrote.

More study needed, but daratumumab injection may work earlier in ITP

Overall, the findings support daratumumab as a potential treatment for ITP, though the researchers emphasized that further studies will be required to more thoroughly explore the medication’s efficacy and identify optimal dosing regimens.

The team further noted that “the consistent, durable responses and favorable safety profile suggest that daratumumab would have utility beyond the refractory setting,” meaning it could help patients whose disease isn’t hard to treat. The researchers noted that “its use earlier in the disease course … warrants exploration.”