Dr Kuykendall on Evolving JAK Inhibitor and Transplant Considerations in Myelofibrosis

“The biggest unanswered question [regarding JAK inhibitors and transplants in myelofibrosis] asks, how do we time transplants?”

Andrew Kuykendall, MD, an assistant member in the Department of Malignant Hematology at Moffitt Cancer Center, discussed considerations for JAK inhibitor sequencing and the use of transplant in myelofibrosis.

At the 2026 Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma meeting, Kuykendall and colleagues discussed changing treatment considerations and debate points within the myeloproliferative neoplasm continuum. Regarding the sequencing of JAK inhibitors and the role of transplant in the treatment of myelofibrosis, Kuykendall emphasized that one of the most important unanswered questions surrounding JAK inhibitor use and allogeneic stem cell transplant was the optimal timing of transplant referral and intervention. He noted that although transplant remains the only potentially curative option for patients with myelofibrosis, it was also associated with substantial morbidity and mortality, making treatment decisions particularly complex in transplant-eligible patients.

Kuykendall explained that many patients initiate therapy with a JAK inhibitor and subsequently experience meaningful improvements in symptom burden, splenomegaly, and overall quality-of-life (QOL). This dynamic created a clinical dilemma, as the point at which patients were deriving the greatest benefit from JAK inhibition could also represent the most favorable time from a disease-management standpoint to proceed with transplant. However, patients were understandably less inclined to pursue transplant during periods of symptomatic improvement, he said.

Kuykendall added that transplant decision-making extends beyond disease risk alone and required careful consideration of QOL tradeoffs. According to Kuykendall, the first year after transplant is often associated with reduced QOL, which could overlap with a period during which patients might otherwise continue to do well on JAK inhibitor therapy.

Regarding JAK inhibitor sequencing, Kuykendall stated that questions persist despite the availability of 4 FDA-approved JAK inhibitors. Since these agents are not strictly line-specific based on their regulatory indications, he suggested that clinicians should move away from a rigid frontline/second-line framework in favor of individualizing therapy based on patient-specific needs and treatment goals.

Kuykendall highlighted anemia management as one example of this personalized approach, noting that clinicians might switch from ruxolitinib (Jakafi) to momelotinib (Ojjaara) in the setting of worsening anemia, then potentially transitioning back if the patient’s symptoms were better controlled with the original therapy. Although payer and authorization barriers could complicate this strategy, he maintained that current JAK inhibitor selection is best guided by matching the most appropriate agent to the individual patient, rather than adhering to a predefined sequencing algorithm.