Educational content on VJHemOnc is intended for healthcare professionals only. By visiting this website and accessing this information you confirm that you are a healthcare professional.

A session with experts Ruben Mesa & Naveen Pemmaraju, who discuss the latest updates in myeloproliferative neoplasms (MPNs) from the 2021 ASH Annual Meeting.

Welcome to The MPN Sessions brought to you by the Video Journal of Hematological Oncology (VJHemOnc). This exclusive discussion features leading experts Ruben Mesa & Naveen Pemmaraju, who debate key updates in the treatment and management of MPNs, including myelofibrosis, polycythemia vera and essential thrombocytopenia, following the 63rd ASH Annual Meeting and Exposition.

Comments on ASH and hybrid meetings

 

“But I think through the miracles of technology and medicine, we’re all vaccinated, masking up and patient. Trying to have patience with each other, we’ve been able to pull this off. I find it to be not only miraculous but necessary. We’ve been able to get back into exchanging new ideas, new collaborations, new inspirations. Ruben, it turns out that just doing Zoom meetings for two years, doesn’t spark the intellect and inspiration as much.”


– Naveen Pemmaraju

Role of TP53 in MPN transformation to AML

 

“It seems to herald the transformation to AML leukemia and worse so there may not be a whole lot we can do to directly prevent it at this time, except to understand that the combination of inflammation, so tissue injury, picking up mutation or mutations, and then some people will then go to AML leukemia. That was a big talk here at the Plenary Session, suggesting that single-cell analysis in the lab can kind of predict what these cells are going to do before they show up clinically.”


– Naveen Pemmaraju

Implementing discoveries in MPNs into clinical trials

 

“The UK groups, multiple groups in England and across the world, collaborating with our groups in Texas and New York and beyond. And what’s really great, and you are really one of the pioneers of this, is taking discoveries in the MPNs and then putting it into all the clinical trials.”


– Naveen Pemmaraju

Updates in ET

 

“In ET, I was very excited in seeing the report from Italy, a multicenter study. There’s a parallel study at our institution at the Mays Cancer Center with the LSD1 inhibitor, IMG-7289.”


– Ruben Mesa

Updates in PV

 

“Ropeginterferon, Besremi, now US FDA-approved as of a week or two ago, really pioneered in Europe by our friends, Jean-Jacques Kiladjian and Dr Gisslinger, so I’m excited that a new formulation of interferon, an injectable for our patients, is out.”


– Naveen Pemmaraju

Updates in MF

 

“The issue with the two approved JAK inhibitors is that, at least in terms of package label and the way we all studied it, there’s a platelet cut-off, whatever it is, 50, let’s say, for these two. So below that, there’s really not a JAK inhibitor there. So this agent, pacritinib, has been shown that it can still be given safely and feasibly even in patients with low platelets, so I think that’s very exciting.”


– Naveen Pemmaraju

Combination therapies in MF

 

“You have the bromodomain inhibitor, pelabresib, as you mentioned. The second one, as you know, I’m very much involved in the ruxo plus navitoclax data that you and I are both a part of, that’s Bcl-xL. But Bcl-xL is still not yet FDA approved. It’s in active clinical trials. So that agent, in combination with ruxo, is now in Phase III studies, the TRANSFORM studies. We eagerly await those data. And then, finally, as you mentioned, the PI3 kinase inhibitor story, parsaclisib, also in combination with ruxo, also going into Phase III studies. Those are in the frontline setting, but then you also have the imetelstat agent.


– Naveen Pemmaraju

Exciting new developments for MPNs in the future

 

“I think the granularity, the details, will be important because there will be multiple options and how we use them and how we really tailor that to the care of an individual that may have a complex disease journey will be critical. The second that we’ve not yet seen, but really excites me, are the various strategies that are being planned; vaccine, CAR-T, immunologics around CALR mutated disease.”


– Ruben Mesa

Watch the full session
Full Transcript

Ruben Mesa:

Hello, I’m Ruben Mesa. I’m the executive director of the Mays Cancer Center at UT Health San Antonio MD Anderson and joined here by my wonderful friend, colleague, and global MPN expert, Associate Professor of leukemia at the MD Anderson Cancer Center, Naveen Pemmaraju. So Naveen-

Naveen Pemmaraju:

Thank you, Ruben.

Ruben Mesa:

A lot of things going on at this ASH as it relates to MPNs. I think you have a variety of things for us to discuss. But, first, what are some of your takeaways from the hybrid experience? For those that have not had a chance to travel here, we know what a live meeting looks like. We know what now a bunch of virtual meetings have looked like over this time of the pandemic. Any takeaways from hybrid?

Naveen Pemmaraju:

Well, Ruben, that’s a great place to start because you and I have seen it all in these last two years. We’ve conducted virtual-only two-day conferences and those work well for people who can’t come or are not able to due to health or geography. This ASH is the first of its kind, a true hybrid event.

Naveen Pemmaraju:

We have sessions together that you and I have been in where the two moderators are remote, oftentimes in different countries. The presenter is remote on a prerecorded video. Technical glitches that have followed, as expected.

Naveen Pemmaraju:

But I think through the miracles of technology and medicine, we’re all vaccinated, masking up and patience. Trying to have the patience with each other, we’ve been able to pull this off. I find it to be not only miraculous but necessary. We’ve been able to get back into exchanging new ideas, new collaborations, new inspirations. Ruben, it turns out that just doing Zoom meetings for two years, doesn’t spark the intellect and inspiration as much.

Ruben Mesa:

It truly does not, no. From my end, I’m incredibly grateful. One, that we’ve been able to come here and be present. Truly, the majority of on-site attendees I would say are from the US at this point, just through the difficulties of travel.

Ruben Mesa:

But it would have been not nearly as enriching an experience and we clearly would not have had the depth of science without really all of our international colleagues being here, as well, virtually. So I think we’ll learn more but I think, over time, we’ll clearly get the sense that the moderators and presenters ideally present as much as possible-

Naveen Pemmaraju:

Right.

Ruben Mesa:

I think is key. I think being able to absorb and interact with a meeting remotely, technology can well support. I don’t think it supports necessarily the intersection of multiple remote presenters-

Naveen Pemmaraju:

Right.

Ruben Mesa:

For a live audience.

Naveen Pemmaraju:

Right.

Ruben Mesa:

That it falls short on. Well, why don’t we share just a bit on the science side?

Naveen Pemmaraju:

Okay.

Ruben Mesa:

So we had the Plenary Session today that I know, I just saw your tweet just very recently that came out as it relates to the role of p53, potentially, in why MPNs progress to AML. Maybe just share a word or two. What are some of the takeaways from that? Is that just biology at this point or anything you think we can really do if I order NGS on someone next week and I see p53, should I freak out?

Naveen Pemmaraju:

Oh, this is great. I’m glad you started off on that. This is something you and I have talked about for many years. It’s really cool to see our MPN sessions highlighted at ASH. There’s five, maybe six oral presentations at ASH this year, including being on the Plenary once again.

Naveen Pemmaraju:

The key concept that you just brought up is important. Chronic diseases don’t stay chronic all the time as you and Serge, and many others have shown. So if you have an MPN, particularly myelofibrosis, the worry, the danger, the risk is that it can go to leukemia. We see it all the time in the clinic.

Naveen Pemmaraju:

The question here at ASH over the last two years is can we predict it? Can we do something about it? And can we ward it off altogether? So this is kind of really nice work that builds on the work of our colleagues in New York, Drs Ross Levine, Raajit Rampal, our colleagues and friends, where there’s something called TP53, the guardian of the genome. It gets hit. It gets lost. It gets messed up. And now these cancer cells start to proliferate.

Naveen Pemmaraju:

And in our MPN, unfortunately, that seems to be very important. It seems to herald the transformation to AML leukemia and worse so there may not be a whole lot we can do to directly prevent it at this time, except to understand that the combination of inflammation, so tissue injury, picking up mutation or mutations, and then some people will then go to AML leukemia. That was a big talk here at the Plenary Session, suggesting that single-cell analysis in the lab can kind of predict what these cells are going to do before they show up clinically.

Ruben Mesa:

Very good. Well, very important progress and exciting to see truly how many important discoveries from MPNs have really been discussed at the Plenary Session-

Naveen Pemmaraju:

Right.

Ruben Mesa:

At ASH, so it’s just a sign of the depth of the kind of scientific focus, some of the great scientific firepower that’s from that wonderful Oxford Molecular Medicine Institute-

Naveen Pemmaraju:

Right.

Ruben Mesa:

That has really had a tremendous history and impact over the years, so exciting.

Naveen Pemmaraju:

It, also, what you’re talking about is important because it highlights the cross-continental collaborations we’ve all had.

Ruben Mesa:

Yeah.

Naveen Pemmaraju:

Right? The UK groups, multiple groups in England and across the world, collaborating with our groups in Texas and New York and beyond. And what’s really great, and you are really one of the pioneers of this, is taking discoveries in the MPNs and then putting it into all the clinical trials.

Naveen Pemmaraju:

For example, you pioneered the MPN symptom burden, the so-called TSS score. You must be gratified. I was going to say this to you anyway, but now we’re on camera. I saw your work on every single clinical trial showing the decrease in the MPN symptom burden. What is that like 10, 15 years later after you came up with that?

Ruben Mesa:

Well, it’s really grateful and gratifying to see. It’s, clearly, many involved with that amazing work by Amylou Dueck, our statistician, who was key with that. Robyn Scherber and others and clearly patients. But what’s great is we walked this journey. Because at first there were a lot of people who pushed back, including journal reviewers, that symptoms aren’t a big deal.

Naveen Pemmaraju:

Right.

Ruben Mesa:

In fact, the first paper I had data on symptoms from 1500 patients and it was refused by a reviewer who said, “Well, you know, I have three patients and they don’t have symptoms.” So, I guess, the patients are lying?

Naveen Pemmaraju:

Oh, wow.

Ruben Mesa:

So to see that evolution where now we have validated tools where it’s really become the standard, both in trials and in practice, has been really gratifying.

Naveen Pemmaraju:

Wow.

Ruben Mesa:

And I think-

Naveen Pemmaraju:

Wow.

Ruben Mesa:

It just gives us insight that I think the really next level is what does it tell us about biology?

Naveen Pemmaraju:

Yes.

Ruben Mesa:

Because I think there’s a link to biology. There are, undoubtedly, issues in terms of depression, anxiety, and others that can factor in, without question. We’ve done some of that work, as well. But there’s really a biology piece.

Ruben Mesa:

Now, one of the areas that we saw that was very interesting is we pivot a bit toward therapies. The great thing of this ASH is that there’s really some interesting updates in ET, PV and MF. Before we get to MF where there’s always the lion share. Drugs are really kind of vetted in that most difficult group. In ET, I was very excited in seeing the report from Italy, a multicenter study. There’s a parallel study at our institution at the Mays Cancer Center with the LSD1 inhibitor, IMG-7289.

Naveen Pemmaraju:

Yes.

Ruben Mesa:

And ET has been a somewhat of a difficult space. There’s a lot of patients, maybe 150,000-200,000 in the US. We have Hydrea, we have anagrelide, interferon off-use, a little bit of ruxolitinib off-label. But the bench is fairly thin.

Naveen Pemmaraju:

Right.

Ruben Mesa:

So this is a nice study. And I would say that our experience and our ongoing study is similar. In patients with hydroxyurea failure really showing this different mechanism of action, the ability to both control the platelet count, improve symptoms-

Naveen Pemmaraju:

Right.

Ruben Mesa:

And potentially have a little bit of a deeper impact on the disease, so it’s early going.

Naveen Pemmaraju:

Right.

Ruben Mesa:

We also know, I presented a poster yesterday of our now accruing Phase III study, shamelessly plugged here in this video, the SURPASS ET study where your colleague, Srdan Verstovsek and I-

Naveen Pemmaraju:

Yes.

Ruben Mesa:

Are leading. Ropeginterferon now approved in PV compared to anagrelide for second-line therapy. So new therapies upcoming in ET. Now in PV we again see some potential new options, particularly these hepcidin mimetics. Why don’t you share with the folks a little bit of what that rusfertide data looks like, but why hepcidin? Why would we want to give a hepcidin mimetic?

Naveen Pemmaraju:

What an exciting conversation, because you really tied in nicely the elements of biology and in the lab, and then the patient-centered journey which you and I have always been so focused on. Again, with the symptom burden, spleen size reduction, and then moving the story into the earlier patient journeys about ET and PV.

Naveen Pemmaraju:

PV, all a sudden now, an exciting time for our patients and caregivers, Ruben, hasn’t been necessarily the case over the last decade. The two developments that you mentioned, the ropeginterferon, Besremi, now US FDA-approved as of a week or two ago, really pioneered in Europe by our friends, Jean-Jacques Kiladjian and Dr Gisslinger, so I’m excited that that new formulation of interferon, an injectable for our patients, is out.

Naveen Pemmaraju:

But the PTG-300, the rusfertide, that’s the new agent really being discussed here at ASH. So the principle is in P vera, too many red blood cells, too much iron imbalance, homeostasis is not right. And so now we’ve been phlebotomizing our patients, asking them to do the long blood draws. Nobody likes that.

Ruben Mesa:

Yeah.

Naveen Pemmaraju:

The doctors don’t like that. The patients don’t like that. The family members don’t like that. And it’s a transient maneuver. So scientists, including some of our colleagues said, what about something like a continuous phlebotomy state? Can you make that iron imbalance normal again? Can you tell iron and blood cells to not be so active and go back to their spaces that they belong to whether it’s the liver or the blood or wherever?

Naveen Pemmaraju:

So this drug, rusfertide, PTG-300, tries to mimic that process through an agent called hepcidin, which tries to tell the iron system, “Hey, take it easy. Have some balance here.” Interestingly, it’s also a once-a week-injectable, which is already common in our field, anyway. That’s interesting.

Naveen Pemmaraju:

And what we saw today in sort of back to back oral presentations in our session today is not only this agent works to decrease the phlebotomies or actually eliminate it in many of the patients, but that there’s scientific correlative data to suggest it’s actually doing what we thought.

Naveen Pemmaraju:

It is actually normalizing the iron levels. It is actually bringing down these ferritin and hepcidin balance level. So I think the bottom line is, is that trial is in an ongoing Phase II. And then, as with all of our trials, let’s let that get into the Phase III, the larger setting, so we can see more data, see if this is something we can bring to patients one day.

Ruben Mesa:

So exciting updates in ET and PV and possibly some new therapies soon, but certainly ropeginterferon for those that have not used interferons yet, I think will really have a really favorable impact.

Naveen Pemmaraju:

Right, right.

Ruben Mesa:

It has a fairly broad label. Now let’s favor a bit toward myelofibrosis. The energy of drug development always really begins with myelofibrosis.

Naveen Pemmaraju:

Right.

Ruben Mesa:

I think because the patients really can have a lot of burden of disease. It clearly has the greatest impact in terms of your both morbidity and mortality. So let’s first start with the drug that’s approved, but many folks haven’t yet quite had an experience with it, which is fedratinib. We heard from Vikas Gupta today, some updates from the FREEDOM study that I, I believe you guys are involved with it, as well.

Naveen Pemmaraju:

Right.

Ruben Mesa:

That is looking at now kind of the experience, post-approval in a study setting. And both related to toxicities as well as the issue with thiamine.

Naveen Pemmaraju:

Right.

Ruben Mesa:

So any takeaways from that that might be reassuring for folks that have been sitting on the sidelines waiting to write that first prescription for fedratinib?

Naveen Pemmaraju:

Yeah. For me it was very exciting to see that. This is Dr Vikas Gupta, our friend and colleague in Toronto, Canada. Beautiful talk today on the so-called FREEDOM trial, Phase IIIb. So exactly, as you said, Ruben, kind of the drug is already approved and in our hands. But to the credit of the sponsor, you, Claire Harrison, all of the investigators, let’s keep looking at safety and tolerability. That was the focus of Dr Gupta’s talk.

Naveen Pemmaraju:

I was excited by it because he showed three things. One is we know about the GI toxicity signal already part and parcel with the drug. He gave some practical mitigation maneuvers. “Hey, when you’re prescribing this drug a little bit of patient education, doctor education, some preemptive prescriptions for nausea, vomiting, et cetera.” That was very helpful.

Naveen Pemmaraju:

Number two, the big story, which you, Claire Harrison and others reevaluated was that there was a signal for Wernicke’s encephalopathy, a potentially serious, maybe even a fatal disorder involving vitamin B1 or thiamine deficiency.

Naveen Pemmaraju:

Your reanalysis showed that that may not be so much of an issue and this helped us to understand that. Yes, you should check thiamine levels. You should replace them, but it’s not going to stop us in prescribing this medication. I was very pleased to see that and he showed those levels over time.

Naveen Pemmaraju:

Then a third part. This is only the second of two agents, FDA-approved JAK inhibitors in our entire field. You helped to pioneer the first one, ruxolitinib. This is the second one. So now we know in longer follow up, it’s safe, it’s effective. You can mitigate these fairly tolerable side effects and you should be watching out for encephalopathy, in general, not necessarily the Wernicke’s and it’s something that we can do as a field.

Naveen Pemmaraju:

It’s also important to note that it’s not just another JAK inhibitor. Each of these, and we have the pacritinib and momelotinib in Phase III studies still. Look at the other targets that each of these JAK inhibitors are hitting, and then you can use them in sequence depending on the JAK inhibitor, so it was a very exciting presentation.

Ruben Mesa:

Very true, very true. Folks ask me at this meeting how do I view the landscape for myelofibrosis. Obviously many things in development, many more than ever. So I try to break it into different segments. One, the JAK inhibitor segment. We have two approved drugs and they’re both good drugs. Now we’re celebrating more than 10 years that ruxolitinib has been approved.

Naveen Pemmaraju:

Wow. Right.

Ruben Mesa:

And the impact that it’s had. You think of all the patients that have benefited over this decade, it is tremendous. And last year’s ASH, you guys presented a beautiful paper that really continued to validate the observation that there’s probably a survival advantage for people who are treated on that.

Ruben Mesa:

Now we have two that really are on the cusp of also probably being part of this equation, as we think about optimizing JAK inhibition. The first is pacritinib that we think, and it’s in the public domain, that it hopefully will be available for patients to be commercially prescribed in quarter one of 2022. So where might pacritinib fit in for our MF patients?

Naveen Pemmaraju:

A very important question. The issue with the two approved JAK inhibitors is that, at least in terms of package label and the way we all studied it, there’s a platelet cut-off, whatever it is, 50, let’s say, for these two. So below that, there’s really not a JAK inhibitor there. So this agent, pacritinib, has been shown that it can still be given safely and feasibly even in patients with low platelets, so I think that’s very exciting.

Naveen Pemmaraju:

And then the second aspect, as we were mentioning earlier, is that each of these JAK inhibitors hit different targets. In the case of the pacritinib agent, it hits IRAK and some of these other pathways, which are implicated in what we call the inflammasome or mitosome, and that may have other pleiotropic effects that are still being studied in the lab and in patient samples. So you and I, we see patients every week. We welcome this because each of these agents is not “just another JAK inhibitor.” It gives us another option.

Naveen Pemmaraju:

The other aspect of it is, is what about long-term safety and efficacy? Sometimes those things are observed after a drug is already approved, and that’s something that you and I are comfortable with, why the rux has over a decade now of post-approval data.

Naveen Pemmaraju:

I think the other issue for us is combination therapies, right? And you and I have been part of that. And I wanted to get your take on that, which is combining agents with a JAK inhibitor. What has caught your eye there at this ASH, Ruben?

Ruben Mesa:

Well, I think there’s a lot of exciting things. I think, first, patients will probably be on an optimized JAK inhibitor. We add in the fourth JAK inhibitor, momelotinib, also working against ACVR1. It’s inhibiting hepcidin and might help to improve anemia. And, I think, pacritinib and momelotinib really will factor into the treatment landscape in a range of ways, particularly in patients with thrombocytopenia or anemia or both. Maybe some frontline.

Naveen Pemmaraju:

Right.

Ruben Mesa:

And clearly some second-line, as well. But the combinations are really interesting and there’s multiple. I could, just to list a few; pelabresib, parsaclisib, navitoclax, selinexor. On and on, so many of these different drugs that we’re looking at. The MDM2 inhibitor from Kartos, many of them.

Ruben Mesa:

From my end, I think, one, these drugs may be able to improve the response rates of those things that we have historically valued. A higher degree of spleen or symptom response either in the frontline setting, which is now being asked for navitoclax and pelabresib, but others may go for that untreated group. In this add-on group, if you’re on for a while, you add these drugs on-

Naveen Pemmaraju:

Yes.

Ruben Mesa:

What do you gain? And then, third, we failed rux, now you’re on this drug alone. Now there’s, all are starting to see different potential, additional areas of benefit. Maybe improve cytopenias, maybe improve fibrosis, maybe improve allele burden. All I think need to be viewed with some degree of these are still really exploratory endpoints. We don’t know quite what they are, but I’m excited.

Naveen Pemmaraju:

Yeah.

Ruben Mesa:

I also take a bit of a bird’s eye view and say, what we have is we have a series of Phase II studies with several ongoing Phase III studies, but we truly only have Phase III data in JAK inhibitors at this point. We have no Phase III data yet in any non-JAK inhibitor.

Naveen Pemmaraju:

Right.

Ruben Mesa:

So there is some amount of, we really do need to let these things play out.

Naveen Pemmaraju:

Right.

Ruben Mesa:

See really what the final data is. Because people say, “Well, how are they going to factor in?” I think it’s going to depend.

Naveen Pemmaraju:

Okay.

Ruben Mesa:

I think for my end, it’s going to depend. What was that efficacy exactly? Are there really subgroups? Because we are talking about combination therapies likely will be quite expensive and potentially have other toxicities. But how do you see this evolving in any that you… If you were to say, “Boy, these are the ones that I’m most excited about at this moment,” what would that be?

Naveen Pemmaraju:

Yeah. I like the way you fleshed out and outlined this field because many of our colleagues have been used to just one drug or one class of drugs. Wow, you really nailed it. So the combinations can be in three ways now; upfront JAK inhibitor-naïve, suboptimal response add-on, and then completely relapsed/refractory.

Naveen Pemmaraju:

I really would pick up where you just mentioned, which is in these novel mechanisms of action, you have the bromodomain inhibitor, pelabresib, as you mentioned. So we have some single agent activity with that now being combined. So that mechanism, bromodomain, looks like it modulates MPN cytokines, megakaryocytes, erythrocytes, so maybe at the level of the bone marrow in our patients.

Naveen Pemmaraju:

That combination is very exciting, Ruben, because our colleagues have shown that there may be anemia improvement early on. These are ongoing studies. We want to let everyone know these are in clinical trials. So we want that data to mature, as you mentioned.

Naveen Pemmaraju:

The second one, as you know, I’m very much involved in the ruxo plus navitoclax data that you and I are both a part of, that’s Bcl-xL. Here’s what you were talking about. The fascinating miracles of drug discovery. Everyone out there knows the venetoclax story, Bcl-2, which is now approved in a number of different leukemia states.

Naveen Pemmaraju:

But Bcl-xL is still not yet FDA approved. It’s in active clinical trials. That appears to be active for some reason in our myelofibrosis. So that agent, in combination with ruxo, is now in Phase III studies in the TRANSFORM studies. We eagerly await those data.

Naveen Pemmaraju:

And then, finally, as you mentioned, the PI3 kinase inhibitor story, parsaclisib, also in combination with ruxo, also going into Phase III studies. Those are in the frontline setting, but then you also have the imetelstat agent.

Ruben Mesa:

Sure.

Naveen Pemmaraju:

Which our colleagues including John Mascarenhas in New York are developing. And the key there is Phase III study, relapsed/refractory, but for the first time in our field, overall survival as the primary endpoint, which I know you and I are excited to see. Patient-centered focus, it’s what we started out talking about. Biology, lab science, symptom burden, spleen. How about overall survival? What do you think about that in terms of these new breed of Phase III trials?

Ruben Mesa:

I think it’s key. I think, one, we really need to see the data. As people say, “Well, the initial response rate looks higher than the COMFORT studies.” I always caution a word of-

Naveen Pemmaraju:

Sure.

Ruben Mesa:

Of caution with that. Meaning having put people on those studies, the people that we put on upfront study now are not the people that we put on the COMFORT study. The COMFORT study was, we had no prior effective therapy. So it was people that had the disease for years, sometimes with advanced disease.

Naveen Pemmaraju:

Oh, I see.

Ruben Mesa:

They failed Hydrea, they failed all sorts of things. They didn’t fail the JAK inhibitor. But they’d failed all sorts of things. That is different than the almost newly diagnosed patient. So I do think the control arms of some of these studies may do better than the COMFORT studies had done historically, so we’ll just have to see. But I think it’s all positive. If there’s 10 drugs approved for myelofibrosis, that’s fabulous.

Naveen Pemmaraju:

I’ll take it.

Ruben Mesa:

And people say, “Well, how can that small disease really support all these drugs?” I’m like, “Not to worry.” In part, we know that many of these therapies are really quite innovative, may impact a range of diseases.

Naveen Pemmaraju:

Right.

Ruben Mesa:

I mean, they’re developed in a bunch of things. It’s not that they have to really only exist just based off myelofibrosis.

Naveen Pemmaraju:

Right.

Ruben Mesa:

But our patients are heterogeneous. We know that there’s a lot of patients with unmet need in MPN and MDS, overlap syndromes in more advancing disease, other combinations. So the more options we have, I think the better off we are. It’s not to say that we have a full dance card and-

Naveen Pemmaraju:

That’s right.

Ruben Mesa:

And can’t really develop it any further. So this has been a wonderful update, my friend. Maybe give folks a final thought, exciting thing. What is your most exciting thing you’re looking forward to as relates to MPNs for 2022?

Naveen Pemmaraju:

For 2022, as the pandemic extends, you and I and others have talked about that. I’ve got two takeaway points for our folks out there. One is that despite difficult times that we’ve all faced internationally, here, back home in the States that we must, It’s imperative, it’s a necessity that we continue to meet like this at meetings online, virtual, hybrid if it’s safe.

Naveen Pemmaraju:

Because no matter what’s going on in the world, we must continue our work in these rare blood cancers. Because, Ruben, as you and I have said many times before, if you have a rare blood cancer like myelofibrosis, PV, or ET, it’s not rare to you. That’s what you and your family are dealing with. We must continue what we’re doing. And I’m very proud that our field has moved on despite these last two years.

Naveen Pemmaraju:

The second takeaway is what you said there. I’m eager to see the mature data on the combination studies to see how we deal with overlapping toxicities, low blood counts, dose adjustments of one or the other. And then if and when these get approved in the community setting, looking forward to a few years, how they are done off of clinical trials, right? And I think you and I will be helping to learn, teach, collaborate with people on that. So I think those are my two takeaways. What about for you, Ruben, as we close this?

Ruben Mesa:

No. Wonderful. First, with this unprecedented number of Phase IIIs, I think the data from the Phase IIIs, the correlative studies, will be scrutinized to a tremendous detail. I don’t think that it’s just a matter of what we validated, what we presented at ASH in our Phase II.

Ruben Mesa:

I think the granularity, the details, will be important because there will be multiple options and how we use them and how we really tailor that to the care of an individual that may have a complex disease journey will be critical. The second that we’ve not yet seen, but really excites me, are the various strategies that are being planned; vaccine, CAR-T, immunologics around CALR mutated disease.

Naveen Pemmaraju:

Oh, yeah.

Ruben Mesa:

CALR expressed on the cell surface, at least in theory, seems one that we might be able to address in a slightly different way. Still kind of a proof of concept but, boy, wouldn’t it be exciting if that really makes-

Naveen Pemmaraju:

Yes.

Ruben Mesa:

A very complementary difference to some of the things that have already been developed.

Naveen Pemmaraju:

That’s great.

Ruben Mesa:

Well, great. Well, this has been a wonderful chance for us to chat on VJHemOnc reporting here from ASH of 2021. My friend, Naveen, thank you for joining me.

Naveen Pemmaraju:

Thank you, Ruben.

 

THE MPNs CHANNEL

 

EXPLORE THE LATEST UPDATES IN MPNs, INCLUDING EXPERT INTERVIEWS FROM MAJOR INTERNATIONAL CONGRESSES, PODCASTS AND E-LEARNING.

The MPN Channel on VJHemOnc is supported by Constellation PharmaceuticalsKartos Therapeutics, Inc. and Sierra Oncology.

These supporters have no influence over the production of the content.

Disclosures

Ruben Mesa, MD, has participated in a consultancy role with Novartis, Sierra Onc, La Jolla, Pharma and Constellation; and has received research support from Celgene, Incyte, AbbVie, Samus Therapeutics, Genotech, Promedior, CTI and Constellation.

Naveen Pemmaraju, MD, is a member of the ASH Communications Committee and the ASCO Leukemia Advisory panel; has participated in consultancy work for Pacylex Pharmaceuticals, ImmunoGen, Bristol Myers Squibb, Blueprint Medicines, Clearview Healthcare Partners, Astellas Pharma US Inc., Triptych Health Partners and CTI Biopharma; has received grants from Affymetrix and SagerStrong Foundation; has received honoraria from Incyte, Novartis, LFB Biotechnologies, Stemline Therapeutics, Celgene, AbbVie, MustangBio, Roche Diagnostics, Blueprint Medicines, DAVA Oncology, Springer Science + Business Media LLC, Aptitude Health, NeoPharm Israel and CareDx, Inc., has received research support from Novartis, Stemline Therapeutics, Samus Therapeutics, AbbVie, Cellectis, Affymetrix, Daiichi Sankyo and Plexxikon; and has received travel reimbursement from Stemline Therapeutics, Celgene, MustangBio, DAVA Oncology and AbbVie.