Tomorrow’s Myelofibrosis Therapies

In part four of a roundtable discussion led by Prithviraj Bose, MD, of the University of Texas MD Anderson Cancer Center, experts explore the next wave of therapies for myelofibrosis, with a focus on targeting CALR mutations and improving symptom management. The panel begins by explaining how mutated CALR, which relocates to the cell surface, offers a novel opportunity for targeted treatment in patients with essential thrombocythemia and myelofibrosis. They highlight the emergence of two promising therapies: a monoclonal antibody and a bispecific antibody from. Both therapies are in early-stage trials but are showing encouraging symptom and spleen response rates in CALR-mutant patients.

As the conversation progresses, the experts discuss the broader context of JAK inhibitors and the hope for newer, more effective agents. They emphasize the need for precise patient stratification, particularly for those with anemia. Agents like momelotinib may offer improved outcomes for patients whose primary symptom burden is anemia, guiding treatment decisions and potentially improving quality of life.

The panel also takes a deep dive into the complexities of symptom measurement in myelofibrosis. They discuss the limitations of current tools like the MPN-SAF and TSS50, especially as the field evolves toward non-JAK therapies. Regulatory considerations are addressed, including the potential need for new endpoints such as six-minute walk tests to objectively assess patient benefit.

Finally, the discussion touches on symptom burden related to treatment side effects and the highly individual nature of symptom tolerability. The experts call for collaborative efforts within the field to refine patient-reported outcomes and improve symptom assessment methods in clinical trials and real-world practice.