During a live virtual event, Ruben Mesa, MD, discussed the use and sequencing of JAK inhibitors and stem cell transplant for patients with myelofibrosis.
CASE:
Laboratory Results:
What would be your next step for this patient?
Targeted OncologyTM: How would you approach treating this patient with Janus kinase (JAK) inhibitors and a stem cell transplant?
RUBEN MESA, MD: First, I think the decision for [allogeneic hematopoietic stem cell] transplant is a complex one. I take a generous view of having the transplanters visit with everyone who might be a transplant candidate, either now or in the near future. Second, I’ve found that patients can be quite variable, particularly in their late 60s or 70s, as to whether they want to go through with a transplant. It’s not uncommon for me to see patients that are recommended to have a transplant who decline it, given the complexity that can go with that. Almost all patients are on a JAK inhibitor or have had a JAK inhibitor.
One thing I think we’ve learned over time is that you clearly can be on a JAK inhibitor and then go to transplant, which was questioned at first. Probably the best time to go for transplant is when you’re having your best response to the JAK inhibitor. What we’ve found is that the outcomes are probably worse for transplant as a salvage therapy for the patient who has failed multiple JAK inhibitors. The outcomes are probably best before the patient [wants] transplant. The spleen is smaller, their performance status is better. They probably do better in engraftment; it does make it challenging, but that is probably when they do best.
How do the National Comprehensive Cancer Network (NCCN) guidelines advise treating patients with higher-risk myelofibrosis?
In terms of the NCCN guidelines, as we look at patients with higher-risk disease—which are probably the majority—at this point, we still stratify patients based on their platelet count.1 We have 2 approved agents: ruxolitinib [Jakafi] and fedratinib [Inrebic], and both are FDA approved for platelet counts over 50,000 (50 × 109/L).
It’s recommended for eligible patients to consider transplant, and again, most people do get a JAK inhibitor in that process. If we saw a patient today and recommended they see a transplant specialist, at a minimum it’s going to be 3 months or more before that would occur, which is more than enough time for a JAK inhibitor to give them some benefit and put them in a better position. Three months would probably be quite an aggressive timeline [to receive stem cell transplant].
What is the role of the 2 approved JAK inhibitors in treatment?
Our standard now, for almost a decade—I remember well when ruxolitinib was first approved in November of 2011, and it’s been the cornerstone.2 I monitor for improvements in spleen, symptoms, and of progression. Fedratinib has now been approved since September 2019.3 It is approved in the frontline setting but has probably not been used very often in that setting yet. It’s also approved in the second-line setting. Physicians probably have not had too much experience with fedratinib, but it can be a helpful therapy.
References:
1. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 1.2022. Accessed March 11, 2022. https://bit.ly/3pWfNml
2. FDA approves Incyte's Jakafi(TM) (ruxolitinib) for patients with Myelofibrosis. Incyte. Published November 16, 2011. Accessed March 11, 2022. https://bit.ly/3pZdyyx
3. FDA approves fedratinib for myelofibrosis. FDA. Updated August 16, 2019. Accessed January 31, 2022. https://bit.ly/3dErcBr
Peers Discuss Sacituzumab Govitecan in HR+ mBC Post Endocrine Therapy
July 24th 2024During a Case-Based Roundtable® event, Tiffany A. Traina, MD, surveyed participants on treatment for a patient who had progressed following endocrine therapy for metastatic breast cancer in the first article of a 2-part series.
Read More
Dato-DXd Shows Promise as a More Tolerable ADC in HER2-Negative mBC
July 22nd 2024During a Case-Based Roundtable® event, Igor Makhlin, MD, discussed with participants their impressions of datopotamab deruxtecan as therapy for patients with HR-positive, HER2-negative breast cancer, and the sequential use of multiple antibody-drug conjugates.
Read More
Rossetti Reviews Myelofibrosis Risk Stratification and Outcome Data for Pacritinib
July 17th 2024During a Case-Based Roundtable® event, James M. Rossetti, DO, discussed the role of risk scoring and stratification tools and treatment for a patient with declining hemoglobin and platelet counts due to primary myelofibrosis.
Read More
Similar Efficacy in Melanoma Shown in Indirect Comparison of PD-1/LAG3 vs PD-1/CTLA-4
July 16th 2024During a Case-Based Roundtable® event, Michael A. Postow, MD, discussed an indirect treatment comparison of nivolumab plus relatlimab vs nivolumab plus ipilimumab in patients with advanced melanoma in the first article of a 2-part series.
Read More
Phase 3 VERIFY Trial Investigates Rusfertide’s Potential in Polycythemia Vera
July 16th 2024In an interview, Aniket Bankar, MD, discussed the background, design, and goals of the phase 3 VERIFY trial of the hepcidin mimetic rusfertide for the treatment of patients with polycythemia vera.
Read More
Evolving Roles of Transplant and Quadruplet Therapy in Multiple Myeloma
July 15th 2024During a Case-Based Roundtable® event, Adam D. Cohen, MD, discussed triplet vs quadruplet options for a patient with transplant eligible multiple myeloma and NCCN recommendations in the first article of a 2-part series.
Read More