Naveen Pemmaraju, MD

Naveen Pemmaraju, MD, associate professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the results of combining ruxolitinib (Jakafi) and navitoclax in different high-risk populations of relapsed/refractory myelofibrosis.

In the ongoing phase 2 study (NCT03222609)of ruxolitinib plus navitoclax, over 30 patients who had a suboptimal response to ruxolitinib alone in myelofibrosis have been treated so far. Pemmaraju says the novel findings he presented at the 2020 American Society of Hematology (ASH) Annual Meeting are in the setting of high-risk molecular mutations and cytokine profiling that was built into the trial from the beginning.

For patients with high-risk molecular mutations, it was notable that about half the patients had 2 or more high-risk mutations. The addition of the navitoclax demonstrated clinical benefit for most of these patients. Pemmaraju thinks it is nice to know that even in the presence of high-risk mutations, this combination regimen is still providing clinical benefit.

Other findings from this trial come from an evaluation of patients’ cytokines. Patients with myelofibrosis have an upregulation of these cytokines. These data showed that several of the cytokines were elevated. The new interesting data are that there were a couple of new cytokines that we found that were upregulated in the setting of myelofibrosis and may be modulated by the combination, according to Pemmaraju. He thinks these new cytokines need to be further investigated in this ongoing study as well as other studies, and it will be important to see what the significance is.

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Naveen Pemmaraju, MD, discusses the results of combining ruxolitinib and navitoclax in different high-risk populations of relapsed/refractory myelofibrosis.

Ruxolitinib/Navitoclax Shows Efficacy in Relapsed/Refractory Myelofibrosis

Naveen Pemmaraju, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the next steps for research in the field of myelofibrosis.

During the 2020 American Society of Hematology (ASH) Annual Meeting, 

Pemmaraju presented findings from an add-back strategy

 with ruxolitinib (Jakafi) plus navitoclax that looked promising for the field, but with the development of novel treatment strategies, he says it is important to look for toxicity, particularly with a new treatment like navitoclax. There is always the risk of thrombocytopenia with JAK inhibitors, so it is important to monitor for both these older and newer toxicities.

The second direction for research is determining how to measure success in the post-frtonline setting. Typically, research looks at spleen and symptom improvement, but in the second-line and beyond, other factors may need to be considered, such as progression-free, event-free, and overall survival. Pemmaraju says some of these patients have a more acute course that can be measured in years while others can have a more chronic disease that is measured in decades.

The third factor for the future of myelofibrosis is understanding the disease itself, and Pemmaraju notes the search for novel biomarkers is also an important area for future research in this field as it can provide physicians more clues as to what patients will benefit from treatment.

Naveen Pemmaraju, MD, discusses the next steps for research in the field of myelofibrosis.

Pemmaraju Highlights Next Steps for Research in Myelofibrosis

Naveen Pemmaraju, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the need to move beyond JAK inhibition when treating patients with myeloproliferative neoplasms (MPNs), which he recently covered in a presentation during the Texas Virtual MPN Workshop.

In the MPN field, no targeted agents were available prior to the development of the JAK inhibitor ruxolitinib (Jakafi). Later, other JAK inhibitors were developed and are considered to be efficacious for the treatment of some patients. Pemmaraju notes that not all patients respond to JAK inhibitors, not all patients are eligible to receive a JAK inhibitor, and some patients are intolerant. Overall, JAK inhibitors do not appear to be curative in MPNs, leaving allogeneic stem cell transplant as the only curative treatment in the space, says Pemmaraju.

The addition of novel agents to a ruxolitinib regiment is the new strategy for patients who cannot derive benefit from ruxolitinib alone. Pemmaraju says, novel combinations are already being explored for the treatment of acute and chronic leukemias, and now is the time to try this strategy in MPNs.

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Naveen Pemmaraju, MD, discusses the need to move beyond JAK inhibition when treating patients with myeloproliferative neoplasms. 

Moving Beyond JAK Inhibitors in Myeloproliferative Neoplasms

Naveen Pemmaraju, MD, associate professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the clinical implications of a retrospective analysis of 26 patients with myelofibrosis who received benefit from ruxolitinib (Jakafi) when it was rechallenged.

The take home point from this analysis is that ruxolitinib discontinuation or interruption that is followed by ruxolitinib reexposure is somewhat common in the community setting. In this group of patients, a sizable percentage experienced potential clinical benefit from reexposure to the JAK inhibitor, Pemmaraju says.

The data from this study set us up for a number of different concepts for rechallenging patients with the same JAK inhibitor, Pemmaraju says. There are clinical trials evaluating 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 for selecting an appropriate dose of the subsequent agent.

Pemmaraju says 1 important question that remains is how to sequence these agents for patients with myelofibrosis. This analysis brought forward this question, and it will have to be addressed in the future.

Naveen Pemmaraju, MD, discusses the clinical implications of a retrospective analysis of 26 patients with myelofibrosis who received benefit from ruxolitinib when it was rechallenged.

Evidence Supports Rechallenging of JAK Inhibitors in Myelofibrosis

Naveen Pemmaraju, MD, an associate professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, discusses the current understandings of how myelofibrosis (MF) presents in patients.

MF is a heterogenous disease and can present in a number of different ways, says Pemmaraju. For patients with low-risk disease, according to the International Prognostic Scoring System, MF will present similarly to a chronic disease, such as essential thrombocytopenia or polycythemia vera. Life expectancy can be measured in decades for these patients. However, patients who present with intermediate- to high-risk disease may be ill when they come into the clinic; they present with various symptoms and can become sick quickly from the disease itself.

Naveen Pemmaraju, MD, discusses the current understandings of how myelofibrosis presents in patients.

Naveen Pemmaraju, MD | Authors

Articles

Ruxolitinib/Navitoclax Shows Efficacy in Relapsed/Refractory Myelofibrosis

Pemmaraju Highlights Next Steps for Research in Myelofibrosis

Moving Beyond JAK Inhibitors in Myeloproliferative Neoplasms

Evidence Supports Rechallenging of JAK Inhibitors in Myelofibrosis

Evaluating Prognosis and Treatment Options for Patients With Myelofibrosis