‘The HemOnc Pulse’ Live 2024: Is it Time for New Endpoints in MPN?

This podcast episode features a panel discussion on unanswered questions in myeloproliferative neoplasms (MPN) with Naveen Pemmaraju, MD, an Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center; Ruben Mesa, MD, President and Executive Director of the Atrium Health cancer service line; Sanam Loghavi, MD, an Associate Professor of Pathology at MD Anderson Cancer Center; and Olatoyosi Odenike, MD, a Professor of Medicine and Director of the Leukemia Program at the University of Chicago Medicine.

One core unanswered question lies in the current clinical endpoints for MPN. The panel considered whether it’s time for new response criteria in myelofibrosis (MF) such as anemia improvement, overall survival, progression-free survival, and event-free survival.

“There are only two endpoints that matter: people live longer and better, or both. Everything else is a surrogate,” Dr. Mesa explained. “I don’t think we’ve been limited because of our endpoints. We’ve been limited because we’ve not had the efficacy.”

A “golden era” in MPN is approaching, according to Dr. Pemmaraju, noting such agents as ropeginterferon alfa 2b, rusfertide, and ruxolitinib, among others, including LSD1 inhibitors for essential thrombocythemia (ET); and Janus kinase (JAK) inhibitors fedratinib, pacritinib, and momelotinib in MF.

The panelists also addressed if patient clinical outcomes can be improved when treated with JAK inhibitors by opting for a doublet approach upfront versus a sequential approach.

In response, Dr. Pemmaraju highlighted the TRANSFORM I study that compared navitoclax plus ruxolitinib versus ruxolitinib plus placebo in untreated MF. The combination led to durable responses and spleen volume reduction of ≥35% at week 24.

“While the spleen isn’t the beginning and end of everything in MF, it is a significant component of the disease manifestation,” Dr. Odenike said. “These results open the door for further improvement.”

Next, the panel addressed the diagnostic gaps in prefibrotic MF.

“Diagnostically, prefibrotic MF is commonly diagnosed as ET. That’s one area of concern we need to be careful about,” Dr. Loghavi explained. “The other area is measurable residual disease (MRD) in reverse. A high percentage of patients have TP53-mutated disease. If we get lucky and have an effective therapy, could we have an MRD in reverse approach to this disease? Could we have early intervention for patients who develop clonal evolution?”

The panel concluded the conversation with allogeneic hematopoietic stem cell transplant for patients with MF.

“Our approach is to use human leukocyte antigen typing and risk stratify patients,” Dr. Odenike explained. “If they are higher risk, and otherwise transplant-eligible, we do recommend transplant because these are fatal diseases.”