Closing out their discussion on myelofibrosis management, experts from the John Theurer Cancer Center consider novel therapies under investigation and the future treatment paradigm.
Danielle E. Marcotulli, APN: So…we’ve talked a lot about myelofibrosis, the mechanism and all of the drugs that are currently approved to treat it. What do you think about the future of myelofibrosis treatment, Dr McCloskey?
James K. McCloskey II, MD: I agree, this has been a lot of information. I hope everyone found that as interesting as I did. But I think that the future is even more exciting in this disease, and I think…at Hackensack [University Medical Center], I’ve been the director of the leukemia program now there for 3 or 4 years, I guess, but I really started as the director of the myeloproliferative neoplasm division and…I think that the disease space is just changing so quickly. We have more offers and clinical trial proposals every day than we could possibly ever do. We are declining them despite the fact that our myelofibrosis patient population has grown faster than the other areas of our division, and so there are so many exciting drugs coming, I think. To highlight a few, I think the BET inhibitors are a very exciting class of drugs. The one we’ve been hearing the most about was pelabresib, and that is likely to be the drug probably to make it to commercial use first, I imagine. We saw updated data [at] ASH [the American Society of Hematology meeting] looking at the MANIFEST-2 trial [NCT04603495], which … had several arms. But what we saw [at] ASH was the combination arm up front, so pelabresib or BET inhibitor plus ruxolitinib, where we saw spleen volume responses that were…60% at week 48. So as you recall that…pretty robust numbers. Granted this is phase 2. It’s small, but even more importantly this response was maintained in 80% or more of patients. So, it seems to be a durable response. There are some issues with this drug, in my opinion. I think that it does have some cytopenias that could be problematic.
There are other drugs in development behind pelabresib that don’t have as much of an anemia impact. We are going to have one of those Hackensack. So we’re really excited about that. We also saw updated data on a PI3 kinase inhibitor parsaclisib, which we also had this study at Hackensack. This is a PI3 kinase inhibitor that was looked at as an add-on to ruxolitinib. So this looked at patients who had an inadequate response or did not respond to ruxolitinib and were then continued on ruxolitinib with the addition of this drug, parsaclisib. And we did see at week 24 a 19% reduction in spleen volume. And we also saw their median symptom score decreased by 44%. So this was significant response rates. In that same group of higher-risk patients, and possibly disease-modifying drugs, is navitoclax. This is the BCL-2 inhibitor in development. The randomized phase 3 up-front trial has completed accrual, where we looked at ruxolitinib alone versus ruxolitinib plus navitoclax. Again, we saw some updated data [from] ASH where we saw significant rates of bone marrow fibrosis reproduction. Which, for better or worse…is something that does hint, I think, at least at disease modification.
In that same area like with disease modification and reduction in bone marrow fibrosis and we’ve previously seen data on … that we think that’s a drug that is probably going to come to us both in MDS [myelodysplastic syndrome] and myelofibrosis in the future. And luspatercept. So that’s a drug that we know affects the NF kappa-beta pathway. It has been shown in MDS now to be effective [in] low-risk disease of improving anemias, and we are studying it now in myelofibrosis, where we have seen improvements in anemia. And I think that while it’s not maybe as super exciting and cutting-edge as some of these other new drugs…added to ruxolitinib in the frontline setting, as we’ve been talking about all this time, where anemia limits our ability to treat patients, it may also have the ability to be more disease-modifying by allowing us to maintain ruxolitinib dosing. So we do have the clinical trial in myelofibrosis with ruxolitinib or any JAK inhibitor, in fact. And luspatercept that Hackensack [is accruing] now. So lots of exciting options and I think a very bright future of this disease where we haven’t had new options in so long. So, with that…I wondered if anyone had any final thoughts. Anything else you’d like to share?
Danielle E. Marcotulli, APN: I think…after talking about all of this…we all can agree that it’s so important up front to properly…risk-stratify our patients, careful assessment and response. We have other options now, so if they’re not responding appropriately, I think now is the time that we have to switch to a different agent to see if we can get a better response for that patient and therefore improve their quality of life. And I also think, again, as I said before, just talking about transplant and prognosis up front, I think it’s so important to get these patients in with the right people just to see what their options are down the road and move forward with that.
Geeny Lee, PharmD: I think for me, it’s…an exciting time that we get to discuss 3 different JAK inhibitors…2 of which were approved, and that’s just [the] past few years for the treatment of myelofibrosis, and hopefully more…that will be approved soon. And really with the increasing number of these agents that are available, I think it’s important to really recognize the differences in the toxicity profile between these agents and really try to prevent adverse events with appropriate monitoring and medications if possible and probably treat those [adverse] effects that we see for a safe and effective use of these medications. And I think manufacturers’ prescribing information is always a great resource to just know about adverse events, dose adjustment, and various drug/drug interactions. They do get updated as more data [are] collected over time. So…for our colleagues, I would highly recommend really utilizing those resources as questions come up when seeing these patients on the medications.
James K. McCloskey II, MD: I agree with all that…. The future is really exciting…but the present is really exciting. I think all these drugs being available to us, it’s really going to help our patients. I think the other thing that we…touched upon though is the value of collaboration. I think that I would highlight that. Most of the patients with myelofibrosis who see us at Hackensack, they also have a local oncologist. And I think that there are other myelofibrosis nerds out there, probably in your backyard, who would love to help work with you if you’re a local oncologist. I think that these patients really benefit from seeing a physician at a tertiary center, but then also really benefit from continuing their care with their local oncologist because it’s not easy to get around in New Jersey. Traffic here is not so fun all the time. And…honestly, driving 20 miles could take you half the day sometimes.
So there’s not always a need for that, but I think that patients and providers really benefit from that relationship, collaborating on the care of the patients initially and then the bridging to transplant, but then also, as we mentioned, the clinical trial aspect because…this is such a rare disease that if we’re going to continue to make progress, we have to do clinical research, and by meeting a physician at another center early, it…gets on our radar. It allows us to check in maybe once a year, so we’re getting more patients onto trial, and I think that’s something that…we want and our patients want. So…I think that just to wrap up, I’d really like to thank Danielle and Geeny for contributing. You know they are incredible team members. They make my life better and our patients’ life better. I thank you, the audience, for joining us today and listening. We certainly hope that you found this episode of own OncLive® Inside the Clinic program to be useful and valuable in the management of your patients with myelofibrosis. Thanks a lot.
Transcript is AI-generated and edited for clarity and readability.