New cell therapy brings remission in treatment-resistant ITP in trial
Single-dose infusion led to long-term disease control for 3 of 4 patients
Written by |
Treatment with an experimental single-dose cell therapy in hard-to-manage immune thrombocytopenia (ITP) led to long-term disease control in 3 of 4 people with the rare bleeding disorder, a new study reports.
The researchers stressed that these results, from a clinical trial in China testing treatment candidate PRG-1801, are preliminary and limited to this small number of patients. Still, the team says the early data support the use of this cell therapy as a potentially useful tool to control ITP that does not respond to standard treatment.
“This first clinical evaluation of … [the] cell therapy in four patients with refractory [treatment-resistant] primary ITP demonstrated manageable safety, rapid and sustained platelet recovery, and durable drug-free complete remission lasting up to 15 months, supporting further evaluation in larger studies,” the researchers wrote. Platelets are tiny cell fragments in the blood that help it clot.
The study, “BCMA-directed CAR-T cell therapy induces durable drug-free remission in refractory primary immune thrombocytopenia,” was published as a letter to the editor in the journal Blood. The work was funded by the National Natural Science Foundation of China and other Chinese agencies.
An autoimmune disorder, ITP is marked by antibodies that destroy platelets, which help stop bleeding. Low platelet levels can lead to symptoms such as abnormal bleeding.
Antibodies are produced mainly by immune cells called B-cells. PRG-1801 is designed to deplete B-cells, thereby reducing levels of disease-driving antibodies.
Novel cell therapy targets a different protein
PRG-1801 is an autologous CAR T-cell therapy. This type of treatment involves collecting T-cells, another type of immune cell, from patients, then engineering them in a lab so the cells have a human protein called a chimeric antigen receptor or CAR. The CAR functions like a molecular weapon, directing the T-cells to attack and destroy a specific target.
Several previous studies have explored the use of CAR T-cell treatments in ITP. Prior work has primarily used CARs that target a B-cell protein called CD19. A notable limitation of this approach, however, is that, although most B-cells express CD19, some B-cell subtypes do not, so targeting this protein may not effectively eliminate all cells that make disease-driving antibodies.
PRG-1801 targets a different protein, BCMA, which the scientists said represents a complementary strategy to deplete a wider range of B-cell subtypes.
Now, a team led by scientists in Wuhan is running an early Phase 1 clinical trial (NCT06519565) testing PRG-1801 in people with ITP whose disease has failed to respond to standard therapies. All trial participants are treated with a single infusion of PRG-1801 at one of two doses. A few days before getting the cell therapy, patients are treated with chemotherapies designed to reduce immune cell counts and make room for the therapeutic cells.
As reported in this study, a total of six patients received PRG-1801. However, only four of the participants stayed in the study long term and were available for follow-up.
3 participants saw improvements within 2 weeks
Among the four evaluable participants, 75% (three patients) experienced a complete response to therapy, the data showed.
Prior to treatment, all participants had platelet levels lower than 30 billion platelets per liter of blood. However, within two weeks of receiving PRG-1801, platelet levels for the three increased to at least 100 billion platelets/L. In these three patients, platelet levels remained high as of the latest follow-up, as long as 1.4 years later.
The fourth evaluable participant also initially responded to therapy, but the response was delayed — platelet levels didn’t substantially increase until about a month after treatment. And nine months after treatment, this patient relapsed, with platelet levels dropping back down again. This drop in platelet counts was accompanied by a resurgence of platelet-targeting antibodies, which was not seen in the other three patients.
“In our BCMA CAR-T cohort, three patients achieved [complete response] within 14 days, and these [three] sustained responders remain off ITP-directed therapy for 6-15 months,” the researchers wrote.
Larger prospective studies are … needed to validate this approach, define remission durability, and identify patients most likely to benefit.
Safety data indicated that PRG-1801 was overall tolerated well. The only serious side effects reported were low immune cell counts, which were expected given the treatment regimen. All patients experienced an inflammatory reaction called cytokine release syndrome, but these reactions were mostly mild and were managed with steroid medications.
Overall, the researchers said that PRG-1801 showed encouraging safety and efficacy data, but they stressed that the results “should be viewed as an early clinical signal from a small, highly selected cohort, as only four of six infused patients were evaluable for longitudinal efficacy.”
According to the researchers, “larger prospective studies are therefore needed to validate this approach, define remission durability, and identify patients most likely to benefit.”
