the
5 Big Questions
I Have for MF

This story is best experienced with audio.
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Aaron Gerds, MD

Cleveland Clinic, Taussig Cancer Institute
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Question 01:

How do “The Big Three” affect prognosis?

Written by Kristin Bundy for Scroll Studio
CREDITS
“All of these problems are intricately related.”
— Aaron Gerds, MD

Optimizing care in myelofibrosis is not only difficult because it is a rare disease, it also presents the challenge of treating interrelated symptoms where affecting one may affect the others. This is definitely true of “The Big Three”: low platelet counts, anemia, and enlarged spleen that physicians most often encounter.

Scroll Down

Cytopenic MF manifests through the intricate workings of a negative feedback loop between the disease itself and its many clinical symptoms.

The hallmark characteristic of MF—the fibrous scar tissue that builds in the bone marrow— interrupts the production of blood cells, eventually causing the marrow to fail. As a result, cytopenias develop anemia and thrombocytopenia, which in turn prompt splenomegaly. An enlarged spleen can sequester platelets and red blood cells, which in turn creates more cytopenia.

Meanwhile, the fibrotic scar tissue in the marrow spurs on inflammation, which influences splenomegaly and, in true ouroboros fashion, leads to more fibrosis.

“All of these problems are intricately related,” says Dr. Gerds. “Before you can assess how each individual component weighs in, you need to understand the relationship between them.”

While prioritizing the most dramatic clinical symptom helps to improve quality of life, Dr. Gerds cautions against a narrow view.

“If you’re just focusing on one aspect of the disease and ignoring the rest, you can impede the potential progress an individual can make.”

For example, if a patient presents with a large spleen or heavy symptom burden, just addressing those facets of MF could lead to “trashing the blood counts,” says Dr. Gerds.

Or if a patient is put on blood transfusions for severe anemia but the physician ignores the fact that the patient’s spleen is huge, they are missing out on addressing the splenomegaly that might ultimately help improve the anemia.

Alternatively, if a patient has a JAK mutation, and that is the only treatment target, one risks worsening cytopenias with a JAK inhibitor known to cause myelosuppression.

“Really, I think the holistic approach,” says Dr. Gerds, “which addresses the most pressing issue at hand while looking at the whole picture in each domain, will help physicians come up with the most customized package for each individual.”

PERSONAL STORY #1

"Relationships are important, especially when you grow up in a small town.”

Melvin, MI.

While Many Would Find growing up in a town like Melvin limiting, Dr. Gerds appreciates the perspective it gave him on how to relate to others. And he sees that as a secret weapon in the care of people living with myelofibrosis.

MF doesn't just attack the body; it attacks how patients see themselves, stealing who they are as people and dehumanizing them.

Specialists, like Dr. Gerds, have to excel in science—but they also know that building strong relationships with peers and patients is critical to making that science work.

“Growing up in a small town, I got those nuances of just really connecting with someone from sitting on a back porch with them. There’s certainly something hayseed about it, something folksy, but it’s helped.”

When you grow up in a place where everyone knows you by your first name, you gain a deeper understanding of meaningful connections; connections that improve communication with patients and caregivers; connections that bolster co-treatment with community hematologists-oncologists; connections that accelerate knowledge- sharing with other MF experts around the world.

It’s the kind of chemistry that makes a difference.

“It was a nice upbringing. When your world is small, I think it teaches you really good life lessons when interacting with folks. You’re more careful of what you say, and you try to get along with everyone."

Dr. Gerds jokes that calling Melvin a “town” is a bit of a stretch—it was more like an intersection. But that intersection taught him the importance of knowing how to cross paths with the other people in your life.

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Question 02:

Are “driver” mutations really driving MF?

The discovery of the JAK2 mutation was a huge breakthrough in MF about 15 years ago. Since then, JAK2 has become known as a “driver” mutation for MF. But that moniker doesn’t sit well with Dr. Gerds. “I think it’s a bit misleading to call JAK2 a driver mutation. Yes, the mutation activates the JAK-STAT pathway, but these two components are not always central to disease.” Pathogenesis may rely more on a second mutation found with clonal analyses, or an antecedent type 2 mutation. “Mutations that drive JAK-STAT activation are important, but they are not the whole picture,” says Dr. Gerds.

“Mutations that drive JAK-STAT activation are important, but they are not the whole picture.”
— Aaron Gerds, MD

Indeed, while clinical practice has focused on the JAK2 mutation and JAK2 inhibitors, ongoing research has shown that multiple pathways are likely involved in MF. For example, the TLR/ILR-IRAK1 pathway has been implicated in the increase of proinflammatory cytokines, the RhoA-ROCK pathway is involved in megakaryocyte and platelet formation, and the FLT3-STAT pathway activates genes important for cell survival.

“We need to think about accessory pathways,” says Dr. Gerds, “TGF-β, NFκB, and all the other things that we know are critical in developing scar tissue in the bone marrow and how the bone marrow fails over time. This is such a complex disease; there's a lot more going on there.”

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There is a puzzling paradox in MF—patients who share similar mutations, like the JAK2 mutation or calreticulin mutations, present with various types of symptoms and blood counts.

Take MF, polycythemia vera, and essential thrombocytopenia for instance. They all have the same genotype, but their phenotypes are vastly different, says Dr. Gerds. “So when second, third, and additional mutations were discovered, it made sense that they would be involved in MF.”

The challenge now is figuring out what we know and what we don’t know about mutations that affect the pathophysiology of MF, says Dr. Gerds. What we do know is that in all types of cancers, researchers agree on universal truths around mutations. One is—certain mutations are always problematic, like the P53 gene, which is the most frequently altered gene in all cancers. Another universal truth is— the more mutations, the more aggressive the disease.

But we can only detect the mutations we know about, explains Dr. Gerds.

Researchers are trying to address the complexity of MF and tease out the unanswered questions, like how many mutations are involved in the disease? What are their roles? How do accessory pathways impact JAK-STAT, TGF-β, and NF-κB? How does the bone marrow fail over time? How do those mutations ultimately lead to those outcomes? “We have our panels, but we’re probably still missing critical mutations for MF, and those don’t account for epigenetic changes—genes that are not necessarily mutated but are turned on or off in those cells.”

Good news is some answers are trickling in, says Dr. Gerds. Studies have shown that certain mutations are associated with early disease progression in MF. Among patients with smoldering diseases, newly developed somatic mutations can speed-up disease progression, and these mutations are different from those seen in patients with early disease progression.

“We’re starting to link different genotypes with the actual disease course of an individual. It is very exciting. But we have a long way to go.”
— Aaron Gerds, MD

PERSONAL STORY #2

“I’ve had my own drivers in my life. Here are some who influenced me.”

“If I were to thank everybody who’s influenced me, it would be worse than the Oscars. They’d be pulling the hook for sure.”
— Aaron Gerds, MD

Growth never happens in a vacuum. For us to adopt new ways of seeing the world and adapt to the changing landscape before us, we need to be shaped by multiple perspectives that challenge us to expand to our greatest potential. But was there one central “driver” that started it all off?

Not with Dr. Gerds.
“I suffer from ‘Baby Chick Syndrome.’ The first person I meet in a professional setting, they make an impression and then that’s what I do, just like when a baby chick hatches from an egg and whoever it sees first is its momma.”
— Aaron Gerds, MD
Greater Yale Medical Clinic

As you walk through his hall of fame, there is the perfect mix of personal and professional. People like Bill Nye, The Science Guy. His weird mix of fun and learning got him into science. Then there are high school teachers, like Brian Derowski, who helped shape the way he thinks. A local physician, Dr. Zajac, whom he worked summers with, started him thinking more seriously about medicine. And then, as he matriculated into med school, the influences continued.

Fred Hutchinson Cancer Research
Center from the Space Needle

Dr. Pat Stiff at Loyola taught him how to not only care for patients, but how to conduct and apply clinical trials. Kevin Simpson, MD showed him how to work with people and manage a team. In Seattle, Joachim Deeg, MD, influenced his career tremendously. (“He showed me how to sit with a patient and explain what was going on, and then on the research side, he showed me how to think critically about the literature.”)

Ruben Mesa, MD and Aaron Gerds, MD

As his mentor in his first rotation, Dr. Deeg inspired him on the path of MPNs and, along with Dr. Bart Scott and Ruben Mesa, established a strong springboard for his career. And, of course, there is Dr. Patrick Fahey, who introduced him to the bow tie.

Like the complex factors that affect myelofibrosis, we are the sum of the influential forces in our lives.
“Again, I could go on all day, but ultimately I think it goes back to even earlier: simply my parents and growing up in that small town and all the lessons they instilled in me remain the utmost influence today.”
— Aaron Gerds, MD
Aaron Gerds, MD and his family
Question 03:

How can social media improve MF care?

Rare diseases, like myelofibrosis, can easily isolate patients and caregivers—and even community physicians who may only see a handful of patients each year. For these audiences, social media has become a surprising ally in healthcare, creating supportive communities and making knowledge sharing more immediate and beneficial.

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While patient-run social media pages bring the MF community together, Dr. Gerds says the technology helps him professionally as well.

For instance, over the years, many patients found Dr. Gerds thanks to recommendations from other patients on social media. For patients with rare diseases, who may not even know MPN specialists exist, this connection serves as a vital link to receiving the best care available.

“We can offer treatments to patients who may not have had access to them otherwise.”
— Aaron Gerds, MD

Increasing clinical trial awareness and enrollment is another advantage of social media, says Dr. Gerds. “Thinking about conducting clinical trials and moving the field forward, we can say on social media, ‘Hey, we have this trial open. If you’re a patient with myelofibrosis, you may want to check it out.’ In that way, we can offer treatments to patients who may not have had access to them otherwise.”

Another perk? Patients who participate in social media come to Dr. Gerds’ clinic well-informed about MF, which enriches the conversation between himself and his patients. “Since patients already have the basic knowledge of the disease established, we can spend more time sorting out the finer details,” he says.

“Hey, we have this trial open. If you’re a patient with myelofibrosis, you may want to check it out.”
— Aaron Gerds, MD

In a way, the knowledge patients glean from each other on social media has helped evolve the doctor-patient relationship, says Dr. Gerds.  “As practice moves further away from the paternalistic and closer to a more common model of shared decision-making, we are better able to discuss different options and arrive at a group decision on the best course of action for that individual at that time,” he says.

PERSONAL STORY #3

“Inspiration is crowdsourced so if I made a playlist for those living with MF...”

DR. Gerds says, If I were to build a myelofibrosis playlist, it would be a lot of songs that have that theme woven throughout of, you get knocked down and you get back up and you keep moving forward ‘cause that at the end of the day is what helps improve the lives of patients.

“You get knocked down and you get back up and you keep moving forward ‘cause that at the end of the day is what helps improve the lives of patients.”
— Aaron Gerds, MD
Question 04:

How low should platelet levels drop

before reevaluating treatment?

Treating myelofibrosis can sometimes be like trying to dance to an ever-changing playlist. Physicians can find it difficult to stay ahead, especially as both natural disease progression and treatments can have a consequential effect on critical factors, like thrombocytopenia. Dr. Gerds has become an expert at navigating these tricky dynamics, helping physicians calculate the next best turn while always keeping an eye on the larger map.

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Dr. Gerds thinks about platelet counts in ranges. There are patients with platelet counts >100,000, others in the 50,000 to 100,000 range, then <50,000, and <25,000. It is with these lower numbers, when thrombocytopenia becomes severe, that disease risk and bleeding risk increase, and the ability to use available therapy wanes because it is myelosuppressive, says Dr. Gerds.

His sweet spot for platelet count and treatment strategies hits around 50,000.

“When platelet counts are above, say, 50,000, I’m still pretty aggressive about treatment, but I will watch blood counts more closely and more frequently in those patients.” When patients’ platelet counts dive below 50,000, Dr. Gerds begins to worry about greater bleeding risk. “At that point, I start backing off therapy or adjust therapy, and begin to think about it in a different way.”

Prognosis and thrombocytopenia are interrelated, says Dr. Gerds. “If we think about models that predict outcome in myelofibrosis, such as the MIPSS70 score, thrombocytopenia—platelet counts above or below 100,000—plays a dominant role. And whether we’re talking about individual univariate analysis, or we add in variables to come up with the outcome, platelet counts and severity of thrombocytopenia often rise to the top of prognostic risk stratification.”

But one blood count doesn’t show the big picture.

Platelet counts are dynamic, and the overall trend is always more helpful than any individual number, says Dr. Gerds, especially when factors like infections and fevers can falsely elevate or lower counts. “I tend to ignore platelet counts that are measured in the hospital. Instead, I tell my patients, let’s wait until you’re back in the clinic to see if there truly has been a change.”

That said, if a patient’s platelet count begins to drop for no good reason, say they were at 100,000, then a couple of months later 80,000, then two more months later 50,000, “that is definitely a red flag that something is dramatically changing in their bone marrow, in the state of their disease,” says Dr. Gerds. “As platelet counts become more severe, the disease can definitely become more aggressive.”

PERSONAL STORY #4

“Mastering the complex starting with tying my bow tie.”

For Many, the thought of tying a bow tie, with all its tricky loops and folds, is intimidating. But for Dr. Gerds, mastering the complex is what he does, whether it’s with the heterogeneous science of myelofibrosis or dressing for work. He’s also learned that when you can make the difficult easier to understand, you can make a bigger difference in the lives of patients.

“The bow tie is definitely a conversation starter. I hope it translates to folks that you can talk to me as a person, not just a doctor.”
— Aaron Gerds, MD

To Dr. Gerds, the bow tie is an essential part of his practice. What began as a one-off gag during his residency at Loyola in Chicago, eventually became a symbol of what others thought of him, and what he thought of himself. It instantly says, “Trust me, I’m the science geek,” while, at the same time, calming the anxieties of patients like a knowing smile. And for many of his patients, his bow tie shines like the “S” on a superhero cape.

“I had a patient where there were a lot of questions, so I said, ‘My Spidey sense is telling me this is going on.’ Next thing I know, he gives me a Spiderman bow tie. Now when I walk into my closet it reminds me of him. It’s wonderful.”

Showing up every day and to every appointment with a different colored bow tie (Dr. Gerds’ last count was at least 60 in his closet at home) is not only a symbol of his “nerdy” science persona—it’s a sign of persistence and ceaseless integrity, and a realization that the bond between physician and patient is critical to success - welcome character traits for anyone battling MF.

It’s the sign of someone who thinks highly of his field, and highly of those he treats.

“The bow tie also reminds me of one of my inspirations: Bill Nye the Science Guy. He’s a bow tie guy, too, academic but accessible. So, you can see my bow ties play a bigger role than you think.”
— Aaron Gerds, MD
Question 05:

Where do we go from here?

While bone marrow transplant can be a near miracle for some myelofibrosis patients, it is not the answer for all patients with MF.

And it is especially for these patients that the MF community is eager for the next big breakthrough.

Research is forging ahead, ambitious studies are in the works, and as specialists glean more insight about MF, we get closer to the possibility of helping more patients. However, we may not have to wait for a quantum leap to see meaningful advances in MF care.

“I think the way medicine works, in general, is not by gigantic landslides of improvement, but small steps forward over time,” says Dr. Gerds. “Especially given the complexity of MF and what’s going on under the hood—divergent clinical phenotypes, genetic and somatic mutations, and emerging insights into the different biologies—it’s going to take a series of marginal gains, but we’ll get there.”

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“I would like to think that one day, during my career, we’re going to reminisce about 2021 and say, ‘Wow, remember when we used to do XYZ because we had nothing to offer these folks,’” says Dr. Gerds. For him, hindsight will reveal how the work we put in now to address the hard questions, like identifying signaling pathways beyond JAK-STAT and the role of cytokines, will eventually shape the trajectory of MF into tomorrow.

“The advent of JAK inhibitors changed the treatment paradigm, and new MF drugs are on the horizon,” says Dr. Gerds. “I think we’re going to keep chipping away at this disease, and eventually there will be a point when we look back and say, ‘We still have a long way to go, but look how far we’ve come.’”

“We still have a long way to go, but look how far we’ve come."
— Aaron Gerds, MD

the
5 Big Questions
I Have for MF

This story is best experienced with audio.
Scroll down to continue.

Aaron Gerds, MD

Cleveland Clinic, Taussig Cancer Institute
Scroll Down
Question 01:

HOW DO “THE BIG THREE” AFFECT PROGNOSIS?

“All of these problems are intricately related.”
— Aaron Gerds, MD

Optimizing care in myelofibrosis is not only difficult because it is a rare disease, it also presents the challenge of treating interrelated symptoms where affecting one may affect the others. This is definitely true of “The Big Three”: low platelet counts, anemia, and enlarged spleen that physicians most often encounter.

Show Transcript

AARON GERDS

So, I think thinking about the different clinical factors and how they relate to each other is an important question.

You know, in a very practical sense, we use these clinical measures to estimate prognosis in patients, so I think understanding how splenomegaly is related to anemia is related to thrombocytopenia can help unravel how we think about disease risk.

Because the more aggressive the disease is, the more aggressive we need to be with it in our treatments.

Cytopenic MF manifests through the intricate workings of a negative feedback loop between the disease itself and its many clinical symptoms.

The hallmark characteristic of MF—the fibrous scar tissue that builds in the bone marrow— interrupts the production of blood cells, eventually causing the marrow to fail. As a result, cytopenias develop anemia and thrombocytopenia, which in turn prompt splenomegaly. An enlarged spleen can sequester platelets and red blood cells, which in turn creates more cytopenia.

Meanwhile, the fibrotic scar tissue in the marrow spurs on inflammation, which influences splenomegaly and, in true ouroboros fashion, leads to more fibrosis.

“All of these problems are intricately related,” says Dr. Gerds. “Before you can assess how each individual component weighs in, you need to understand the relationship between them.”

Show Transcript

AARON GERDS

So after we kind of think about well, what’s going on in each of these domains, kind of the next logical question is, well, what’s the most important right now?

You know, I see a patient with a huge spleen and a lot of early satiety, well shrinking the spleen is a major priority. If someone comes in and is otherwise feeling pretty well, you know, maybe some fatigue and some symptoms, but really the low blood counts are the pressing issue, you know, we would want to address that.

And then lastly, if certain cytokine-related symptoms are the most pressing issue, you know a patient has a lot of night sweats, and that’s really the thing that literally keeps them up at night, you know, that’s something that we would want to address directly, because each of these things might have a slightly different treatment approach, and how you prioritize them can help direct what your next step in treatment may be.

While prioritizing the most dramatic clinical symptom helps to improve quality of life, Dr. Gerds cautions against a narrow view.

“If you’re just focusing on one aspect of the disease and ignoring the rest, you can impede the potential progress an individual can make.”

For example, if a patient presents with a large spleen or heavy symptom burden, just addressing those facets of MF could lead to “trashing the blood counts,” says Dr. Gerds.

Or if a patient is put on blood transfusions for severe anemia but the physician ignores the fact that the patient’s spleen is huge, they are missing out on addressing the splenomegaly that might ultimately help improve the anemia.

Alternatively, if a patient has a JAK mutation, and that is the only treatment target, one risks worsening cytopenias with a JAK inhibitor known to cause myelosuppression.

“Really, I think the holistic approach,” says Dr. Gerds, “which addresses the most pressing issue at hand while looking at the whole picture in each domain, will help physicians come up with the most customized package for each individual.”

Show Transcript

AARON GERDS

You know, a lot of credit to the practicing physicians out there. They use their intuition, they use their experience, they say, “Well, gee, this is really out of place and thus it’s the thing that’s probably driving a patient’s quality of life the most. So, this is what we want to tackle first.”

Again, if someone comes in with a ginormous spleen, you know something like a great dane inside their belly, you know that’s going to be really alarming and they’re going to want to do everything they can to shrink that spleen because that’s going to be the most dramatic benefit.

If someone comes in with really low blood counts, you know, what can we do to help manage their disease in spite of these really low blood counts, because severe anemia, severe thrombocytopenia, can be a pretty dramatic type thing, and same with certain symptoms, like again, the night sweat example.

By helping them think through the process and where they want to go with things, so you know, I try to ask questions to get at what’s going on with the patient. Where do you think we should go? What do you think is the most pressing issue for that individual?

The second thing that I try to do when working with a referring physician is educate right? So, I have the luxury of having some time to read and focus on one narrow area of the literature, having the luxury of spending lots of time taking care of a, you know, a very limited disease set.

So, I can use that expertise that I built, as well as the experience that I’ve built and kind of connect and say, “Ok, so here are some subtleties, here are some finer points.” After we identify that goal, we can apply for that individual and come up with a managed treatment plan between the two of us.

Personal story #1

“Relationships are important, especially when you grow up in a small town.”

While Many Would Find growing up in a town like Melvin limiting, Dr. Gerds appreciates the perspective it gave him on how to relate to others. And he sees that as a secret weapon in the care of people living with myelofibrosis.

MF doesn't just attack the body; it attacks how patients see themselves, stealing who they are as people and dehumanizing them.

Specialists, like Dr. Gerds, have to excel in science—but they also know that building strong relationships with peers and patients is critical to making that science work.

Melvin, MI.
“Growing up in a small town, I got those nuances of just really connecting with someone from sitting on a back porch with them. There’s certainly something hayseed about it, something folksy, but it’s helped.”
— Aaron Gerds, MD

It’s the kind of chemistry that makes a difference.

When you grow up in a place where everyone knows you by your first name, you gain a deeper understanding of meaningful connections; connections that improve communication with patients and caregivers; connections that bolster co-treatment with community hematologists-oncologists; connections that accelerate knowledge- sharing with other MF experts around the world.

“It was a nice upbringing. When your world is small, I think it teaches you really good life lessons when interacting with folks. You’re more careful of what you say, and you try to get along with everyone."

Dr. Gerds jokes that calling Melvin a “town” is a bit of a stretch—it was more like an intersection. But that intersection taught him the importance of knowing how to cross paths with the other people in your life.

Question 02:

Are “driver” mutations really driving MF?

The discovery of the JAK2 mutation was a huge breakthrough in MF about 15 years ago. Since then, JAK2 has become known as a “driver” mutation for MF.

But that moniker doesn’t sit well with Dr. Gerds. “I think it’s a bit misleading to call JAK2 a driver mutation. Yes, the mutation activates the JAK-STAT pathway, but these two components are not always central to disease.”

Pathogenesis may rely more on a second mutation found with clonal analyses, or an antecedent type 2 mutation. “Mutations that drive JAK-STAT activation are important, but they are not the whole picture,” says Dr. Gerds.

“Mutations that drive JAK-STAT activation are important, but they are not the whole picture.”
— Aaron Gerds, MD

Indeed, while clinical practice has focused on the JAK2 mutation and JAK2 inhibitors, ongoing research has shown that multiple pathways are likely involved in MF. For example, the TLR/ILR-IRAK1 pathway has been implicated in the increase of proinflammatory cytokines, the RhoA-ROCK pathway is involved in megakaryocyte and platelet formation, and the FLT3-STAT pathway activates genes important for cell survival.

“We need to think about accessory pathways,” says Dr. Gerds, “TGF-β, NFκB, and all the other things that we know are critical in developing scar tissue in the bone marrow and how the bone marrow fails over time. This is such a complex disease; there's a lot more going on there.”

Show Transcript

AARON GERDS

We know that disease can progress over time and change over time, and that’s often due to other mutations that arrive on the scene in different clones over time, and so you would really say that a secondary mutation in, say SRSF 2 or U2F1 driving that disease, you know, maybe from PV or ET into myelofibrosis or myelofibrosis is an accelerator blast phase or in more of a kind of a spent phase where the bone marrow becomes kind of hypocellular and spent, those second third mutations that push those diseases into new phenotypes, are arguably more important than the original quote-unquote driver mutation.

There is a puzzling paradox in MF—patients who share similar mutations, like the JAK2 mutation or calreticulin mutations, present with various types of symptoms and blood counts.

Take MF, polycythemia vera, and essential thrombocytopenia for instance. They all have the same genotype, but their phenotypes are vastly different, says Dr. Gerds. “So when second, third, and additional mutations were discovered, it made sense that they would be involved in MF.”

The challenge now is figuring out what we know and what we don’t know about mutations that affect the pathophysiology of MF, says Dr. Gerds. What we do know is that in all types of cancers, researchers agree on universal truths around mutations. One is—certain mutations are always problematic, like the P53 gene, which is the most frequently altered gene in all cancers. Another universal truth is— the more mutations, the more aggressive the disease.

But we can only detect the mutations we know about, explains Dr. Gerds.

Researchers are trying to address the complexity of MF and tease out the unanswered questions, like how many mutations are involved in the disease? What are their roles? How do accessory pathways impact JAK-STAT, TGF-β, and NF-κB? How does the bone marrow fail over time? How do those mutations ultimately lead to those outcomes? “We have our panels, but we’re probably still missing critical mutations for MF, and those don’t account for epigenetic changes—genes that are not necessarily mutated but are turned on or off in those cells.”

Good news is some answers are trickling in, says Dr. Gerds. Studies have shown that certain mutations are associated with early disease progression in MF. Among patients with smoldering diseases, newly developed somatic mutations can speed-up disease progression, and these mutations are different from those seen in patients with early disease progression.

Show Transcript

AARON GERDS

I think as we go forward, we’re developing more targeted therapies that can address diseases with particular mutations in them, and actually impact the mutant product of those mutations, so I think that’s really important that it’s starting to become therapeutically based now, it’s not just prognosis or something of interest to discuss with a patient. We’re starting to get to the point now where we’re doing trials in these diseases where we’re targeting some of these mutations, so, as time goes along, it’s only going to become more and more important.

“We’re starting to link different genotypes with the actual disease course of an individual. It is very exciting. But we have a long way to go.”
— Aaron Gerds, MD

Personal story #2

"I’ve had my own drivers in my life. Here are some who influenced me.”

As Dr. Gerds discusses, there may be more to what drives MF than the obvious “driver mutations.” He himself is the result of various “driving” forces along the path of his career. Let’s look at some of them.

“If I were to thank everybody who’s influenced me, it would be worse than the Oscars. They’d be pulling the hook for sure.”
— Aaron Gerds, MD

Growth never happens in a vacuum. For us to adopt new ways of seeing the world and adapt to the changing landscape before us, we need to be shaped by multiple perspectives that challenge us to expand to our greatest potential. But was there one central “driver” that started it all off?

“I suffer from ‘Baby Chick Syndrome.’ The first person I meet in a professional setting, they make an impression and then that’s what I do, just like when a baby chick hatches from an egg and whoever it sees first is its momma.”
— Aaron Gerds, MD
Greater Yale Medical Clinic

As you walk through his hall of fame, there is the perfect mix of personal and professional. People like Bill Nye, The Science Guy. His weird mix of fun and learning got him into science." Then there are high school teachers, like Brian Derowski, who helped shape the way he thinks. A local physician, Dr. Zajac, whom he worked summers with, started him thinking more seriously about medicine. And then, as he matriculated into med school, the influences continued.

Fred Hutchinson Cancer Research
Center from the Space Needle

Dr. Pat Stiff at Loyola taught him how to not only care for patients, but how to conduct and apply clinical trials. Kevin Simpson, MD showed him how to work with people and manage a team. In Seattle, Joachim Deeg, MD, influenced his career tremendously. (“He showed me how to sit with a patient and explain what was going on, and then on the research side, he showed me how to think critically about the literature.”)

Ruben Mesa, MD and Aaron Gerds, MD
As his mentor in his first rotation, Dr. Deeg inspired him on the path of MPNs and, along with Dr. Bart Scott and Ruben Mesa, established a strong springboard for his career. And, of course, there is Dr. Patrick Fahey, who introduced him to the bow tie.
Like the complex factors that affect myelofibrosis, we are the sum of the influential forces in our lives.
“Again, I could go on all day, but ultimately I think it goes back to even earlier: simply my parents and growing up in that small town and all the lessons they instilled in me remain the utmost influence today.”
— Aaron Gerds, MD
Aaron Gerds, MD and his family

Question 03:

How can social media improve MF care?

Rare diseases, like myelofibrosis, can easily isolate patients and caregivers—and even community physicians who may only see a handful of patients each year. For these audiences, social media has become a surprising ally in healthcare, creating supportive communities and making knowledge sharing more immediate and beneficial.

Show Transcript

AARON GERDS

I think there are a couple reasons why social media is important in the care of patients with myelofibrosis. First and foremost is patient advocacy and bringing the disease to the forefront of awareness, right? You know, we don’t want to be the fifth in line for succession for the crown like we are, you know, behind myeloma or lung cancer, what have you.

You know, we want to bring MPN’s to the forefront and I think social media can do that by raising our voices. Secondly, you can connect people, so there is a patient of mine who did start a Facebook page and was able to connect with so many people around the world who all have MPN’s and myelofibrosis, and I think that’s so important that people who have rare diseases can go online, meet other folks, and have that shared common experience.

You can walk out the door here of this building and probably find 6 people within 10 minutes who have high blood pressure, you know, that’s a very common shared experience, but myelofibrosis may not be, and that way they can share what’s going on, and really kind of get that group mentality going that yes, we’re all in this together. We can really advocate for ourselves.

While patient-run social media pages bring the MF community together, Dr. Gerds says the technology helps him professionally as well.

For instance, over the years, many patients found Dr. Gerds thanks to recommendations from other patients on social media. For patients with rare diseases, who may not even know MPN specialists exist, this connection serves as a vital link to receiving the best care available.

“We can offer treatments to patients who may not have had access to them otherwise.”
— Aaron Gerds, MD

Increasing clinical trial awareness and enrollment is another advantage of social media, says Dr. Gerds. “Thinking about conducting clinical trials and moving the field forward, we can say on social media, ‘Hey, we have this trial open. If you’re a patient with myelofibrosis, you may want to check it out.’ In that way, we can offer treatments to patients who may not have had access to them otherwise.”

Another perk? Patients who participate in social media come to Dr. Gerds’ clinic well-informed about MF, which enriches the conversation between himself and his patients. “Since patients already have the basic knowledge of the disease established, we can spend more time sorting out the finer details,” he says.

“Hey, we have this trial open. If you’re a patient with myelofibrosis, you may want to check it out.”
— Aaron Gerds, MD

In a way, the knowledge patients glean from each other on social media has helped evolve the doctor-patient relationship, says Dr. Gerds.  “As practice moves further away from the paternalistic and closer to a more common model of shared decision-making, we are better able to discuss different options and arrive at a group decision on the best course of action for that individual at that time,” he says.

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AARON GERDS

Lastly, I think the dissemination of knowledge is really important with social media. Social media has sometimes been coined as the ultimate peer review. You think about journals as peer review, but social media really is.

A lot of times we’ll publish something you know in a journal and then we’ll post it on Twitter, and you know, then we can start a conversation like hey, there’s this new paper looking at, you know, outcomes in patients with myelofibrosis who were on such and such treatment. Yeah, but did you look at the population they included? It wasn’t 30% secondary myelofibrosis, it was 80% myelofibrosis. How do you think that impacted the outcomes?

And then we could start this debate. Well, you know these mutations were prevalent and these weren’t. How did that impact what we see in this population? So, really, we can kind of start to have those conversations. Not just in, kind of continuously and at your own pace, but also globally, right?

So, I think that it’s so important. It transcends time, it transcends, you know,  national and international barriers and borders and can really bring the MPN community together.

Personal story #3

"Inspiration is crowdsourced so if I made a playlist for those living with MF...”

Gerds says, If I were to build a myelofibrosis playlist, it would be a lot of songs that have that theme woven throughout of, you get knocked down and you get back up and you keep moving forward ‘cause that at the end of the day is what helps improve the lives of patients.

“You get knocked down and you get back up and you keep moving forward ‘cause that at the end of the day is what helps improve the lives of patients.”
— Aaron Gerds, MD

Question 04:

How low should platelet levels drop

before reevaluating treatment?

Treating myelofibrosis can sometimes be like trying to dance to an ever-changing playlist. Physicians can find it difficult to stay ahead, especially as both natural disease progression and treatments can have a consequential effect on critical factors, like thrombocytopenia. Dr. Gerds has become an expert at navigating these tricky dynamics, helping physicians calculate the next best turn while always keeping an eye on the larger map.

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AARON GERDS

So thinking about thrombocytopenia and asking questions around it, I think is a really important question. And how low can platelets get before you need to re-evaluate treatment? I think is different from patient to patient. Because if we get back to the whole idea that you want to identify the most pressing issues within a context of an entire patient, you may be more aggressive in one individual versus another when it comes to platelet counts.

So if you have a patient who has very bad splenomegaly and very bad symptoms, you may be willing to tolerate a little bit more thrombocytopenia when you are using, say, a JAK inhibitor, because you know that it’s going to improve their overall quality of life, and someone where, you know they’re maybe not getting that much benefit from a JAK inhibitor, you may be quick to change when their platelets do come down a little bit.

Dr. Gerds thinks about platelet counts in ranges. There are patients with platelet counts >100,000, others in the 50,000 to 100,000 range, then <50,000, and <25,000. It is with these lower numbers, when thrombocytopenia becomes severe, that disease risk and bleeding risk increase, and the ability to use available therapy wanes because it is myelosuppressive, says Dr. Gerds.

His sweet spot for platelet count and treatment strategies hits around 50,000.

“When platelet counts are above, say, 50,000, I’m still pretty aggressive about treatment, but I will watch blood counts more closely and more frequently in those patients.” When patients’ platelet counts dive below 50,000, Dr. Gerds begins to worry about greater bleeding risk. “At that point, I start backing off therapy or adjust therapy, and begin to think about it in a different way.”

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AARON GERDS

So with a lot of things in life, they’re not linear and, you know, being in the clinic with the patients with myelofibrosis, platelet counts and their overall prognosis and really just the challenge of dealing with them and and how I kind of think about it. It’s almost like an S-curve and the two main curves, the inflection points of that S-curve tend to land around, you know, 100 and say, like 50.

So above 100 you know the change in what’s going on with them is very flat. Whether we’re talking about a platelet count of 100 or platelet count of 400, you know, the way we apply treatments, the way we think about their prognosis, you know the complications they may be having with their disease is all about the same, and then clearly there’s some sort of change that happens at 100, and as you get down to 50, and when you get below 50,000, you know the phenotype of the patient is very similar, you know, the complications and side effects they may have from their disease, how we apply therapies, you know, the daily questions that they’re asking when they come see you so, clearly there are these two different entities and then in between there is a bit of a straight line there where you’re sliding down from 100 to 50, and so it almost makes this S shaped curve when you’re thinking no matter what domain of myelofibrosis you’re thinking about. Whether you think about applying treatments, you’re thinking about prognosis, you’re thinking about effect on quality of life.

Prognosis and thrombocytopenia are interrelated, says Dr. Gerds. “If we think about models that predict outcome in myelofibrosis, such as the MIPSS70 score, thrombocytopenia—platelet counts above or below 100,000—plays a dominant role. And whether we’re talking about individual univariate analysis, or we add in variables to come up with the outcome, platelet counts and severity of thrombocytopenia often rise to the top of prognostic risk stratification.”

But one blood count doesn’t show the big picture.

Platelet counts are dynamic, and the overall trend is always more helpful than any individual number, says Dr. Gerds, especially when factors like infections and fevers can falsely elevate or lower counts. “I tend to ignore platelet counts that are measured in the hospital. Instead, I tell my patients, let’s wait until you’re back in the clinic to see if there truly has been a change.”

That said, if a patient’s platelet count begins to drop for no good reason, say they were at 100,000, then a couple of months later 80,000, then two more months later 50,000, “that is definitely a red flag that something is dramatically changing in their bone marrow, in the state of their disease,” says Dr. Gerds. “As platelet counts become more severe, the disease can definitely become more aggressive.”

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AARON GERDS

You know, maybe we can, for an individual, slowly gear up or slowly gear down, you know, if I start you on a therapy, and I see the counts are coming down, well maybe we make a soft adjustment as opposed to like slamming the brakes on everything.

I think, you know, knowing for each individual treatment the kinetics of what we expect what the blood counts too is really important. We know that with some drugs there are initial dips and then recoveries, and trying to factor that in as opposed to like adjusting too quickly or slamming the brakes on that treatment.

I’ve definitely seen a lot of patients in that, kind of fall in that category where their counts are very up and down, up and down, even before they start on treatment, so I think taking that into account, will help you focus in on the dose, too. The hardest thing I think in this profession is to do nothing, right? You see some problem you want to fix it. This is going on. I gotta change it. I gotta adjust what I’m doing.

We tend to be very proactive, I think, just by nature, right? But the harder thing to say is, like, let’s just give this a little more time. You know, I see this little change in accounts, this could just be variation, let’s recheck in a couple of weeks, or you know, let’s give it another month, let’s kind of ride this out a little bit, because things may settle out. Again, I think if sometimes you can get a little jumpy and you end up chasing your tail.

Personal story #4

“Mastering the complex -- starting with tying my bow tie.”

For Many, the thought of tying a bow tie, with all its tricky loops and folds, is intimidating. But for Dr. Gerds, mastering the complex is what he does, whether it’s with the heterogeneous science of myelofibrosis or dressing for work. He’s also learned that when you can make the difficulty easier to understand, you can make a bigger difference in the lives of patients.

“The bow tie is definitely a conversation starter. I hope it translates to folks that you can talk to me as a person, not just a doctor.”
— Aaron Gerds, MD

To Dr. Gerds, the bow tie is an essential part of his practice. What began as a one-off gag during his residency at Loyola in Chicago, eventually became a symbol of what others thought of him, and what he thought of himself. It instantly says, “Trust me, I’m the science geek,” while, at the same time, calming the anxieties of patients like a knowing smile. And for many of his patients, his bow tie shines like the “S” on a superhero cape.

“I had a patient where there were a lot of questions, so I said, ‘My Spidey sense is telling me this is going on.’ Next thing I know, he gives me a Spiderman bow tie. Now when I walk into my closet it reminds me of him. It’s wonderful.”

Showing up every day and to every appointment with a different colored bow tie (Dr. Gerds’ last count was at least 60 in his closet at home) is not only a symbol of his “nerdy” science persona—it’s a sign of persistence and ceaseless integrity, and a realization that the bond between physician and patient is critical to success - welcome character traits for anyone battling MF.

It’s the sign of someone who thinks highly of his field, and highly of those he treats.

“The bow tie also reminds me of one of my inspirations: Bill Nye the Science Guy. He’s a bow tie guy, too, academic but accessible. So, you can see my bow ties play a bigger role than you think.”
— Aaron Gerds, MD

Question 05:

Where do we go from here?

WHILE BONE MARROW transplant can be a near miracle for some myelofibrosis patients, it is not the answer for all patients with MF.

And it is especially for these patients that the MF community is eager for the next big breakthrough.

Research is forging ahead, ambitious studies are in the works, and as specialists glean more insight about MF, we get closer to the possibility of helping more patients. However, we may not have to wait for a quantum leap to see meaningful advances in MF care.

“I think the way medicine works, in general, is not by gigantic landslides of improvement, but small steps forward over time,” says Dr. Gerds. “Especially given the complexity of MF and what’s going on under the hood—divergent clinical phenotypes, genetic and somatic mutations, and emerging insights into the different biologies—it’s going to take a series of marginal gains, but we’ll get there.”

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AARON GERDS

There’s this whole concept in in professional cycling about marginal gains, where if you can tweak this aerodynamic principle on this bike or you know, drop a gram or two from that bike and pedal in a slightly different way, you might improve your watts by like a few watts you know going at 40 miles an hour or what.

Medicine is often like that. It’s a lot of very small wins. You know, in the trenches pushing very slowly forward, and I think that’s going to be the same for myelofibrosis given the complexity of the disease.

“I would like to think that one day, during my career, we’re going to reminisce about 2021 and say, ‘Wow, remember when we used to do XYZ because we had nothing to offer these folks,’” says Dr. Gerds. For him, hindsight will reveal how the work we put in now to address the hard questions, like identifying signaling pathways beyond JAK-STAT and the role of cytokines, will eventually shape the trajectory of MF into tomorrow.

“The advent of JAK inhibitors changed the treatment paradigm, and new MF drugs are on the horizon,” says Dr. Gerds. “I think we’re going to keep chipping away at this disease, and eventually there will be a point when we look back and say, ‘We still have a long way to go, but look how far we’ve come.”

“We still have a long way to go, but look how far we’ve come."
— Aaron Gerds, MD