Real-World Evidence Supports Ruxolitinib Reinitiation in Myelofibrosis


Naveen Pemmaraju, MD, discusses the potential benefit of rechallenging ruxolitinib in patients with myelofibrosis. 

Naveen Pemmaraju, MD

The treatment of patients with myeloproliferative neoplasms (MPNs) continues to evolve with ongoing research efforts, said Naveen Pemmaraju, MD, especially when it comes to the optimization of JAK inhibitors in myelofibrosis.

At the 2020 ASCO Virtual Scientific Program, findings from a retrospective analysis of 26 patients with myelofibrosis who were rechallenged with ruxolitinib (Jakafi) showed that retreatment with the JAK1/2 inhibitor led to symptom improvement and reduction in splenomegaly.

In an interview with OncLive, Pemmaraju, an associate professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed the potential benefit of rechallenging ruxolitinib in patients with myelofibrosis.

OncLive: Could you shed light on the current treatment paradigm of myelofibrosis?

Pemmaraju: Myelofibrosis is a fairly aggressive and rare hematologic malignancy. It consists of a heterogeneous group of diseases that [fall under the category of] MPNs. The majority of patients with myelofibrosis have a JAK2 mutation, followed by CALR or MPL mutations.

We currently have 1 class of approved drugs in myelofibrosis, that being JAK2 inhibitors. Ruxolitinib was the first drug from that class that was approved. Several other JAK2 inhibitors are either approved or in phase 2 or 3 clinical trials.

Now we have 5- and 7-year follow-up data [with these agents]. In clinical practice, JAK2 inhibitors are stopped for a variety of reasons including toxicity, patient/physician choice, and implementation of stem cell transplant.

What was the rationale for this retrospective analysis of patients with myelofibrosis who were rechallenged with ruxolitinib?

I, along with my collaborators and colleagues, wanted to focus on the early outcomes of patients who were rechallenged with ruxolitinib. It’s a question that is being asked in both academic and community centers.

What methods were used, and what patients were included in the analysis?

It is oftentimes difficult to capture these data, so we looked at 2 large, independent patient-care data resources using available databases. One was the Cardinal Health Oncology Provider Extended Network (OPEN) database. The other was the HealthCore Integrated Research Environment (HIRD) database.

This was a retrospective review, as we are accustomed to in our field. In terms of inclusion criteria, patients had to be at least 18 years old and have a diagnosis of myelofibrosis. The years [that we established]–2012 to 2016 and 2013 to 2017–were important because we wanted to capture the era of JAK inhibitors. We wanted to see what the patterns of interruption and the outcomes were for patients who were rechallenged with ruxolitinib.

Overall, 26 patients met this fairly rigorous retrospective criteria. Most interruptions were as expected and due to toxicities. This was followed by the physician or patient choosing an alternative therapy, disease progression, no response to ruxolitinib, and loss of response to ruxolitinib.

What are the key takeaways from the findings?

The key takeaway is that after restarting ruxolitinib, the median retreatment duration was 196 days and 166 days in each database. Interestingly, patients experienced symptom improvement at 45% [in the OPEN database] and 43% [in the HIRD database]. Spleen size also improved in 40% and 33% of patients, respectively.

The take-home point is that ruxolitinib discontinuation or interruption followed by ruxolitinib reexposure is somewhat frequent in the community setting. In our group of 26 patients, a sizeable percentage of individuals experienced some potential clinical benefit after reexposure.

What are the clinical implications of these findings? What future research efforts are needed in this space?

This sets us up for a number of different concepts [to evaluate] regarding rechallenging patients with the same JAK inhibitor. There are now clinical trials investigating the benefit of sequential or subsequent JAK inhibitor therapies. As these agents are approved, determining the optimal dosing of the initial JAK inhibitor will be important to determine that of the subsequent JAK inhibitor. Additionally, how do we sequence these agents for our patients? These are important questions the analysis raised that will have to be addressed in the future.

Why is it important to conduct retrospective analyses?

It is important to conduct retrospective studies of these novel targeted molecules in rare tumor types. We always want large, randomized, prospective clinical trials. They remain the gold standard. However, in rare tumor types, it may not always be possible to do that. As such, it is important to glean insights from large, retrospective reviews and other smaller studies to generate hypotheses and obtain novel insights that can be confirmed in larger studies.

I want to encourage my fellow investigators and collaborators to continue looking for these new ideas that may be embedded deep within large and small databases, perhaps even at your own institution.

In that same breath, I want to emphasize the importance of understanding how those databases are constructed, who the stakeholders involved in creating them are, and whether multiple authors can vouch for the integrity of the data. How is the data constructed? For this particular project, it was gratifying to have multiple stakeholders involved.

Additionally, retrospective analyses are inherently flawed because they are not prospective. The data sets may not have all the features we need, so the data could be incomplete. However, I have spent a lot of my career working on [retrospective] data and small data sets, so their importance continues to be highlighted into 2020 and will likely continue into the future.

Is there anything else that you would like to add?

The concept of patient advocacy and information in the modern era is important, particularly as it pertains to patients and caregivers who face rare cancers on a daily basis. Just the names of some of these diseases can boggle the minds of those discussing them. For example, one rare tumor type is blastic plasmacytoid dendritic cell neoplasm (BPDCN). Outside of MPNs and acute myeloid leukemia (AML), BPDCN is an area I specialize in.

A few other investigators and I started a hashtag on Twitter, LinkedIn, and other modalities. The hashtag #BPDCN is not run by anybody since it is a grassroots [movement], but it has allowed us to facilitate a discussion among patients, caregivers, and health care stakeholders with very little spam.

If one goes on to Twitter or another social media platform, they are able to follow that [hashtag] and access information directly as it is happening at major medical meetings, interpretations from journals, and discussions among experts. Patients can also reach out to ask general questions.

We've done the same thing in the MPN space with #MPNs on social media. The concept is to get information out there that is accurate and from experts directly to those who are searching for it. A simple Google search does not always provide the latest, cutting-edge information. Additionally, [these hashtags] are ways for people to have real-time discussions. Keeping conversations general, and collegial seems to put the best information out there.

Of course, there are pitfalls to social media. People can get into difficult situations like violations of privacy, so we must aim to respect our patients' privacy.

Specifically, I have found that directing our message of rare tumor research, latest clinical findings, and latest medical conference findings through social media, particularly via Twitter, has been a powerful and effective tool for our patients and caregivers.


  1. Pemmaraju N, Yu J, Parasuraman S, et al. Ruxolitinib (rux) retreatment in patients (pts) with myelofibrosis (mf): real-world evidence on pt characteristics and outcomes. 2020;38(suppl 15; abstr e19535). doi:10.1200/JCO.2020.38.15_suppl.e19535
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