Antibody boosts platelets, shows ‘rapid and sustained efficacy’ in immune thrombocytopenia
Click Here to Manage Email Alerts
Key takeaways:
- Most treated patients had two consecutive platelet counts of at least 50 × 109/L within 8 weeks of the first dose.
- Median time to first platelet count at or above the threshold amount of 1 week.
Treatment with the novel antibody CM313 boosted platelet levels and demonstrated long-term durability among adults with immune thrombocytopenia, results from a phase 2 study showed.
The findings, published in The New England Journal of Medicine, also detailed mostly low-grade toxicities associated with the treatment.
“Achieving an initial platelet response that is sufficient to prevent bleeding and ensuring durable treatment-free remission remain challenges in managing [immune thrombocytopenia],” Yunfei Chen, MD, from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, and colleagues wrote. “In our study, 95% of the patients with [immune thrombocytopenia] ... had platelet counts of at least 50 × 109 per liter during CM313 treatment. This response was rapid, was observed in all but one patient within the first week after the start of treatment, and was sustained for a median cumulative response duration of 23 weeks,” they added. “A total of 86% of the patients with a sustained response maintained platelet counts above 50 × 109 per liter from the initial infusion to the end of the study, which underscores the encouraging efficacy of CM313 in treating [immune thrombocytopenia].”
Researchers conducted a phase 1/phase 2 open-label study assessing the efficacy and safety of CM313 — an investigational anti-CD38 monoclonal antibody — in 22 adults with immune thrombocytopenia.
Study participants received IV CM313 at a dose of 16 mg/kg every week for 8 weeks, followed by a 16-week follow-up period.
Adverse events and documentation of two or more consecutive platelet counts of at least 50 × 109/L within 8 weeks after the first dose of CM313 served as the study’s primary outcome measurements; researchers also monitored the status of peripheral-blood immune cells in patients and changes in the mononuclear phagocytic system in passive mouse models of immune thrombocytopenia receiving anti-CD38 therapy.
Of the 22 patients in the study, 21 had two consecutive platelet counts at or above the threshold during the treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17-24).
Further results showed a median time to first platelet count of at least the threshold amount of 1 week (range, 1-3).
The most common treatment-related adverse events included infusion-related reactions (32%) and upper respiratory tract infection (32%).
Following CD38-targeted therapy, study investigators observed decreases in peripheral blood immune cells.
Researchers acknowledged several limitations, including the study’s nonrandomized, noncontrolled design, a need for extended follow-up because some patients’ immunoglobulin levels had not recovered by the 16-week follow-up period and the absence of an active mouse model for immune thrombocytopenia for mechanism exploration.
Additional studies will look to potentially adjust for these limitations, while also growing its sample size, according to researchers.
“In this study involving patients with [immune thrombocytopenia] who had previously received multiple therapies, CM313 was safe and showed rapid and sustained efficacy in 95% of the patients,” researchers wrote. “A randomized, placebo-controlled trial evaluating CM313 in a larger [immune thrombocytopenia] cohort is under way.”
Collapse
Chen Y, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2400409.
Click Here to Manage Email Alerts