Early Data Support INCA033989 in CALR-Mutant Myelofibrosis: Claire Harrison, MD

Early signals may help identify which patients with myelofibrosis are most likely to benefit from INCA033989, explained Claire Harrison, MD, of Guy's and St. Thomas' NHS Foundation Trust, during an interview with The American Journal of Managed Care^® following the European Hematology Association 2026 Congress. She also discussed key next steps for the therapy and what clinicians should watch for as phase 3 trials get underway.

INCA033989 is an Fc-silent monoclonal antibody that binds the mutant calreticulin protein where it complexes with the thrombopoietin receptor and is displayed on the cell surface, creating a precise immunotherapeutic target. Harrison explained that the agent has the potential to address an unmet need for patients with myelofibrosis harboring mutant calreticulin.

She first discussed early insights into which patients with myelofibrosis may be most likely to benefit from INCA033989, while emphasizing the need for caution when interpreting findings from the early-phase study. Harrison explained that the therapy appears active across both major types of calreticulin alterations: type 1 mutations, which are associated with a more favorable prognosis in the absence of additional mutations, and type 2 mutations, which generally carry a less favorable prognosis.

Although both groups responded to INCA033989, she noted that patients with type 2 mutations may require higher doses. Harrison emphasized that further research is needed to determine whether differences in response are related to protein density, binding characteristics, or other biological factors.

She also highlighted the therapy’s encouraging safety profile. The study did not reach a maximum tolerated dose, and no dose-limiting toxicities were observed. While the current need for intravenous infusions may be a consideration for patients, the development of a subcutaneous formulation could provide a more convenient administration option in the future, Harrison said.

She added that responses were also observed among patients with additional mutations, suggesting that INCA033989 may have broad activity across different molecular subgroups. However, Harrison noted that larger studies will be needed to better define which patients are most likely to benefit.

Looking ahead, she described INCA033989 as a potentially significant advancement in the treatment of mutant calreticulin–positive myelofibrosis. Harrison compared the excitement surrounding the agent’s development with the introduction of ruxolitinib in myelofibrosis more than a decade ago, highlighting the potential for a new treatment approach that directly targets the underlying disease biology.

As phase 3 studies begin, she said clinicians should watch for additional efficacy and safety data, as well as enrollment opportunities for patients who may benefit from participation.

“I'm super excited to see the development of INCA033989,” she said. “I think it represents a step change in the type of treatment that we have to offer our patients. I've got patients queuing up to go on this agent.”