publication date: Jan. 31, 2020

Conversation with The Cancer Letter

Thomas Lynch lists his areas of emphasis at the Hutch:

Solid tumors, immuno-oncology, Big Data, microbial involvement

Thomas J. Lynch Jr

Thomas J. Lynch

President and director, Fred Hutchinson Cancer Research Center

 

On Feb. 1, Thomas J. Lynch will report to work as president and director of Fred Hutchinson Cancer Research Center.

Lynch, an expert in lung cancer, will be taking over the institution which initially established its singular reputation in hematologic malignancies, but which has been strengthening its research in solid tumors.

Lynch’s most recent job was at Bristol-Myers Squibb, where he served as chief scientific officer until late 2019, when the company merged with Celgene. At BMS, Lynch led research and development in cancer, cardiovascular disease, fibrosis and immuno-science.

“I know in hematologic malignancies, if you look at the work of [former Hutch President and Director] Gary Gilliland, it is all about finding and understanding the genes that are driving leukemias. He brings together basic fundamental science with clinical acumen, and look at what an amazing impact that’s made for patients who have leukemia,” Lynch, who holds the Raisbeck Chair for the President and Director, said to The Cancer Letter.

“I think we need to do more of that in solid tumors. And that’s not just an issue about the Hutch. I think that’s true with all of American oncology. We need to make translational oncology a big part of what we do as we move forward, and I’ve tried to emphasize that at Yale, at Bristol-Myers, at MGH, and I’m going to make that a big part of what we do here at the Hutch.”

Lynch said an expansion of research into solid tumors will be one of the four areas of emphasis for his time at the Hutch. The other three are:

  • “Continuing the incredible emphasis on immuno-oncology, and by that I mean cellular therapies, checkpoint inhibitor therapy, broadening the patients that can benefit from cellular therapies in solid tumors as well as heme malignancies. That’s going to be very important.

  • “Big Data projects in science are still very much in their infancy. But the ability to look at patient outcomes through electronic medical records and link that to the proteome, to their genome, to their microbiome will give us opportunities that that we never had before, and being at the Hutch, in the city of Seattle, with so many partners here who are at the vanguard of machine learning and AI-enabled research paradigms will be a great enabler of this research.

  • “The Hutch is going to make big strides in [the] concept of microbial involvement in malignancy. It’s not just the common viruses that we traditionally have known, such as HPV, HIV and Epstein-Barr virus, but really thinking more broadly about the role that bacteria and fungi can have in developing cancer and how the makeup of the microbiome can impact  cancer incidence, progression as well as a predilection to autoimmune diseases.”

Prior to joining BMS as an executive, Lynch served on the company’s board of directors while also serving as chairman and CEO of Massachusetts General Physicians Organization. Prior to that, he was the director of Yale Cancer Center, physician-in-chief of Yale’s Smilow Cancer Hospital, professor of medicine at Yale School of Medicine, chief of hematology-oncology at Massachusetts General Hospital, and professor of medicine at Harvard Medical School.

During his first stint at Mass General, Lynch was part of the team that discovered the role of the EGFR gene in lung cancer, focusing the use of the AstraZeneca drug Iressa (gefitinib) on a specific population (The Cancer Letter, April 30, 2004).

 

Lynch spoke with Paul Goldberg, editor and publisher of The Cancer Letter.

 

Paul Goldberg:

First of all, welcome back to academic oncology.

Thomas J. Lynch:

Thank you. It’s something that I feel incredibly excited about. The opportunity at the Hutch is absolutely remarkable—Paul, you’ve been following cancer for decades, writing about it, reporting on it—and I really do believe that we are poised to make significant strides in how we treat and prevent cancer over the next 10 to 15 years.

So, this is a great time to be doing this.

 

PG:

What have you learned in the pharmaceutical industry?

TL:

I certainly enjoyed my time at Bristol-Myers Squibb. What I learned in the industry is how rapidly progress can be made when coordinated teams bring focused resources to solve a defined problem. 

At Bristol-Myers Squibb and many other companies, cancer is a major focus.  It makes up a lot of the R&D spend, but I also appreciated how people who work in industry are driven every day by  the unmet need in cancer—just like we are in hospitals and academia.

I also recognize, though, from my time in the pharmaceutical industry that there’s an important ecosystem between what happens in fundamental basic science at a place like the Hutch, or at Harvard, or at Yale and what happens in biotech and what happens in big pharma. Bottom line is that we need new ideas that come from transformational basic science—much of which happens in the academic setting.

So, that delicate relationship between the academic world and the biotech world and the pharma world is really important to bringing new treatments to patients, and not just treatment of cancer, but also thinking of ways that we can detect cancer earlier, and possibly prevent cancers from occurring in high-risk individuals. So, all of them really need each other to survive and to thrive.

 

PG:

Let’s go back to when we first started talking—you were at Mass General, working on EGFR.

TL:

Right, exactly. If you look at that example, we were working with a pharmaceutical company and doing trials on gefitinib at that time.

Yet, it was the fundamental observations by [MGH Cancer Center Director] Dan Haber in a basic science laboratory that really made the important finding about EGFR mutations driving sensitivity to gefitinib.

Then the industry took that and went forward, and now we have inhibitors of EGFR, which are extremely sensitive and unique and specific for mutations. So, it’s a really nice example of how clinical observation, basic science laboratories, translational science and pharmaceutical science really come together.

I think one of the things, Paul, that’s been a theme that I’ve worked on at Bristol-Myers Squibb, at Mass General, at Yale, and now at the Hutch is strengthening our translational infrastructure to be able to make those kinds of observations, and I think that that’s going to become very important.

I know in hematologic malignancies, if you look at the work of [former Hutch President and Director] Gary Gilliland [(The Cancer Letter, Sept. 20, 2019)] it is all about finding and understanding the genes that are driving leukemias. He brings together basic fundamental science with clinical acumen, and look at what an amazing impact that’s made for patients who have leukemia.

I think we need to do more of that in solid tumors. And that’s not just an issue about the Hutch. I think that’s true with all of American oncology. We need to make translational oncology a big part of what we do as we move forward, and I’ve tried to emphasize that at Yale, at Bristol-Myers, at MGH, and I’m going to make that a big part of what we do here at the Hutch.

 

PG:

Every cancer center is unique. How would you describe the Hutch, and its scientific focus, and its culture?

TL:

I think, Paul, the good news is I’m learning that. I’m learning that every time I interact with the faculty, and I think a couple of things come to mind.

One, it’s fiercely independent. I think that the scientists at the Hutch are very focused on cancer and viral diseases, and the thing I really like about the people that I’ve been meeting and the science they are doing is they are unconstrained in thinking about the limits of what they can possibly accomplish.

Again, that independence, that unconstrained nature of what kind of science they are going to pursue, to me, is really, really important.

I still think, Paul, that if we’re going to make major breakthroughs in cancer, there’s still so much about cancer that we don’t understand. I think you’ve got to have a place in the cancer research infrastructure and cancer research ecosystem where really smart scientists in population science, in clinical science, and, importantly, in basic science are able to think about pathways and scientific problems in a way that they can follow their observations and their findings, and not be driven just by concerns of how do we bring a drug to market or how do we look at populations for potential indications of existing drugs.

So, I think one thing I’ve been struck by is really that independence of thought here and how powerful that is across the board.

I think second is the faculty are remarkably intense and fiercely committed to improving outcomes in cancer.

The focus of the institution is extremely well-positioned for where cancer is right now. If you think about it, this is the birthplace of bone marrow transplant. It’s had a huge impact in areas of cellular therapies, and now you’re seeing an increase in thinking about solid tumors.

The arrival of [President and Executive Director of Seattle Cancer Care Alliance, Senior Vice President, Director Clinical Research Division at Fred Hutch, and Raisbeck Endowed Chair for Collaborative Research] Nancy Davidson has made an enormous difference at the Hutch and the focus that we’ve been able to develop in breast cancer [(The Cancer Letter, Oct. 14, 2016)].

The fact that the Hutch obtained a SPORE in lung cancer last year is a great example of that, and we have a great prostate cancer program as well.

I think a lot of people, when they think of the Hutch, think of an incredible transplant center and a great place for hematologic malignancies, which it is. Please… I mean, that is definitely a strong suit here, but I’m also impressed by the depth that’s present in solid tumors, and as a solid tumor oncologist myself, that’s definitely an area that I want to pursue and continue to strengthen at the Hutch.

I think, Paul, one other thing which I think distinguishes the Hutch from other places is the focus on cancer prevention is very strong here as well. It’s not just about treating cancers, but it’s about identifying high-risk patients and investigating, are there ways that we could help prevent cancer?

When you look at the tools that are available to us now, in terms of tech, data, and cancer science, an intersection of those three things, I think, prevention might be a place where we see some of those breakthroughs happen even faster than in treatment areas. I think at the Hutch as a cancer center, prevention is a major part of what happens.

I guess the last thing, Paul, just to emphasize that the Hutch isn’t just cancer. It has a very strong program in virology as well, and HIV is a major focus of the faculty here.

The impact of various different microbial pathogens on the development of malignancy is something which I think the Hutch is very well positioned to look at, both in terms of what drives oncogenesis, but also the microbiome and how that determines who develops cancer and how cancers can occur in that setting.

So, I think those are all unique features of the scientific direction of this place. This is truly a special place.

 

PG:

If we go back to EGFR, because that’s an example of research that is not a drug company project. In fact, you were showing how AstraZeneca could sell drugs to a smaller population [than the population that was being targeted at the time]. Because you were really showing the mutation, the Iressa susceptibility gene. You were focusing in on a population Iressa actually was likely to help, as opposed to giving it to everyone with metastatic lung cancer, which seemed to be the [company’s] plan at that time.

TL:

Yeah, and also, I think, Paul, if you think back to that example, it also allowed AstraZeneca to develop an even better drug against the EGFR mutations, osimertinib. You could argue that while there are fewer people, maybe in numbers, or a percentage of the yearly new cancers that get it, overall, it probably ends up being a good business decision as well, because people are benefiting for longer periods of time, and I think that that’s something we can be proud of.

With that said, even in EGFR-mutated in lung cancer, a majority of patients are not living more than three or four years. So, there is still much work to be done, and we are not at a position in very many cancers where we can really declare victory yet. I think that that’s one of the things that drives much of the research here, and it certainly has driven my career.

There are still enormous unmet medical needs in cancer. I think we need to always keep that in mind.

 

PG:

How do you see Fred Hutch evolving under your leadership? You mentioned more emphasis on solid tumors, and you also mentioned more translational research.

TL:

There are four things that I really want to think about here.

One is continuing the incredible emphasis on immuno-oncology, and by that I mean cellular therapies, checkpoint inhibitor therapy, broadening the patients that can benefit from cellular therapies in solid tumors as well as heme malignancies. That’s going to be very important.

Second key thing is this intersection between tech, data, and cancer science. We are very early in this process, and I want to stress that it took a decade or more before we saw how incredibly beneficial the Human Genome Project was. Big Data projects in science are still very much in their infancy. So, I think we have to be careful about not overpromising what we can do.

But the ability to look at patient outcomes through electronic medical records and link that to the proteome, to their genome, to their microbiome will give us opportunities that that we never had before, and being at the Hutch, in the city of Seattle, with so many partners here who are at the vanguard of machine learning and AI-enabled research paradigms will be a great enabler of this research.

The third thing is the importance of, as we talked earlier, the focus on solid tumors and precision medicine. I think that still remains very important: to understand the molecular phenotypes and genotypes of both the tumor as well as what the patient brings to the table.

I think that’s going to become increasingly important as we move forward, and then I think the last part that I think the Hutch is going to make big strides in is this concept of microbial involvement in malignancy.

It’s not just the common viruses that we traditionally have known, such as HPV, HIV and Epstein-Barr virus, but really thinking more broadly about the role that bacteria and fungi can have in developing cancer and how the makeup of the microbiome can impact  cancer incidence, progression as well as a predilection to autoimmune diseases. So, I do think that that’s an area of emphasis here at the Hutch.

 

PG:

You mentioned four areas of emphasis. Should we focus on the immunotherapy a little bit longer, look at it a little deeper? Any thoughts, anything you can do that nobody else is doing?

TL:

So, remember, this is the place where cellular therapies really were birthed and the first in bone marrow transplant, which you could argue is the ultimate cellular therapy, and now with the precision of CAR T-cell therapy, I think that this is, again, something that we are going to continue to develop.

What impressed me in my early time in talking to people at the Hutch is more than half of the clinical protocols that are being developed are being developed for patients with solid tumors, with CAR T therapy.

So, we’ve got to extend the potential benefits beyond just those patients who’ve got ALL, or those patients who have lymphoma, but really rather to think about, whether we can develop meaningful cellular therapies for patients with common solid tumors.

And there are a lot of barriers to getting there. Don’t get me wrong, it’s not an easy problem.

Then, once you’ve got the cellular therapy angle, then the question is, How do we incorporate checkpoint inhibitors and other ways of modulating the immune system as well? I know we’ve all been enamored, and certainly my time at Bristol-Myers Squibb, I spent a tremendous amount of time on PD-1 as a potential target, but I think it’s going to be deeper than PD-1.

It’s being able to learn how we optimize the innate immune system to be able to drive response. How do we understand how to use agonists in general?”

I think that we are really good at using antagonists of the immune system and finding ways to block PD-1, and therefore take the brakes off the immune response, so that immune responses are allowed to proceed, and patients can benefit.

But how do we convert cold tumors into hot tumors and find ways to derive benefit for patients who are not benefited right now by immune therapy?

So, this will continue to be a major focus of the Hutch and major focus of cancer centers throughout the country, as it should be, because I do think this is an area of investment that we are making, that others are making, too, because I do think that there’ve been enough hints of efficacy there that make it worthwhile looking at.

 

PG:

Is there a way to knock down the price of CAR T, for example?

TL:

I think that the price of CAR T; remember, it’s early in its implementation right now. I think one of the things that the Hutch is, again, at the leadership in the world on is this idea of where is the best place to deliver these therapies.

The Hutch is one of the places in the country that led the implementation of  outpatient bone marrow transplants and limiting the amount of time in the hospital for patients with BMT.

We are at the vanguard, and we are leading in terms of understanding how to manage immune-related side effects from cellular-based therapies, as well as from checkpoint inhibitors. And if you can begin to understand and limit side effects, you will be able to control the cost equation of what some cellular therapies can do.

But, Paul, you are absolutely correct that the cost of therapy will have to be a consideration. What I’ve always found is that when you find treatments that work and treatments that are able to deliver meaningful benefits to patients, we will find a way as a health care system to deliver those, and that’s our obligation as a cancer center, to find ways to do that. I really believe that, and it’s our obligation as a society to be able to find ways to do that.

 

PG:

How does Seattle Cancer Care Alliance fit into what you’ll be doing?

TL:

Seattle Cancer Care Alliance will be absolutely crucial to the mission of the Hutch. I really look at them as very much integrated into this incredibly important partnership. Seattle Children’s Hospital and the University of Washington are both incredibly important partners in the consortium research grant, our cancer center.

Our CCSG, our NCI designation, is made to this consortium of these institutions and Seattle Children’s and then—plus—it’s the places where our clinical outlets are—through the Seattle Cancer Care Alliance.

So, Paul, my career, I worked in, at both MGH and Yale, but we are working very closely with hospital systems in terms of thinking about how can we deliver care in the best way possible. I could not be more proud of what I’ve learned in the early days about the care delivered at the Seattle Cancer Care Alliance. Continuing to  enhance and grow this relationship is one of my highest priorities.

 

PG:

Could we talk about the relationships between academic oncologists and the industry? For example, do you believe that a director of a cancer center can serve on corporate boards? By way of disclosure, I don’t feel entitled to an opinion on that myself.

TL:

So, let me just say a couple of things for disclosure. As you probably know, I did serve on the board of Bristol-Myers Squibb for about three-and-a-half years or so before I joined management at Bristol-Myers Squibb. I no longer serve on a large pharma board, and my thoughts are that this would likely create issues of conflict with a major cancer center. 

I had the opportunity to serve on a large publicly traded board, and I currently am the chair of the board of Kleo Pharmaceuticals.

I do want to emphasize that there are many benefits that come from enhancing the relationship between industry and academia. I think there’s a tremendous amount that one can learn from being on a corporate board. I think I certainly learned a lot about leadership, governance and management, and how to approach uniquely challenging problems from being on the board of Bristol-Myers Squibb.

Yet, I think it’s also important that the mission of the cancer hospital or cancer center, depending upon the circumstance, is one that is the primary focus of the director. I felt that way when I was at Yale, and I certainly feel this way at the Hutch, and I look forward to working with the Hutch team and our board of trustees to determine what the best policies for that are.

 

PG:

So, you’re pretty much open-minded about the whole thing?

TL:

I keep an open mind, and one has to evaluate each circumstance on its individual merits and be very careful and cautious about what kinds of things you permit. I think it’s different for cancer center directors than it is for CEOs of health systems than it is for individual investigators.

I think we do want to encourage important scientific relationships between our investigators and industry. That’s been extremely important in the advances against cancer. I think that we don’t want to lose those relationships as we move forward.

 

PG:

Maybe we should focus on that a little bit longer. Should there be an expanded role for what some cancer centers, including MGH, I think, call “external innovation?”

TL:

And can you just explain exactly what you mean by external innovation?

 

PG:

I think that’s a term that’s used, meaning the faculty expending a certain amount of effort on fostering external relationships focused on innovation.

TL:

I think, one of the things I think that the Hutch is very proud of, Mass General’s very proud of, Yale is very proud of are the biotech companies that have come from the faculty at all three of those institutions. I think that the fact that there is a vibrant venture capital community in life sciences that is enabling innovation externally from the actual hospitals or cancer centers, I think is a very, very good thing.

What I think you want to be sure of is that there’s a distinction made, so that patients understand what the potential conflicts of interest could be and that the institutional conflict of interest is managed.

But I do believe that what the Hutch, Harvard, and Yale, among others, have done in external innovation has been something that’s helped to drive much of the success we’ve seen in biomedicine over the past 20 years.

 

PG:

We’ve been writing a lot about theft of intellectual property from academic institutions. What are your thoughts about this problem and ways to manage it?

TL:

Obviously, it’s a problem that has received significant attention from the NCI and federal authorities. I think intellectual property is extremely important, that we guard it very carefully.

We don’t want to inhibit scientific innovation, so I think that we want to make sure that we do this in a way that does not prevent great science from being done. Yet, it’s important that that IP be respected and protected, and there’ve been some high-profile cases that allege theft of IP, and that’s something I think that not only do the institutions have an interest in, but the federal government has an interest in.

With that said, the vast majority of scientists are doing the right thing, and they are doing their science in a way that advances the potential for impacting human health and aren’t involved in IP theft.

But it is something that, again, I’m new to the Hutch, so I need to learn more about what the Hutch is doing specifically about this. I can tell you that it’s important to me. It’s important to the Hutch, that we have the right safeguards in place to make sure that IP does not end up in the wrong hands.

As a society, I think the United States has contributed a tremendous amount to scientific advancement, and I think we want to make sure that American science is able to continue to thrive and to get the recognition that it needs while it continues to play a leading role globally.

 

PG:

Could we talk about community outreach and engagement? It’s an important part of the CCSG, and centers seem to find very different ways, very diverse ways to fulfill this requirement. What’s the Fred Hutch approach to outreach and engagement?

TL:

This is something which Fred Hutch is particularly strong in, and engaging with the community, that we serve in our catchment area is a very important part of what we do, that health equity is at the very center of the mission of the Fred Hutch.

Again, I’m continuing to learn more about this. I know, a lot of cancer center directors lament the challenges of the CCSG process. However, I do think that the community outreach and engagement has been a really good example of how the CCSG can help solidify and enhance commitments to community outreach.

I can tell you that it’s always been a big part of what happens at the Fred Hutch, and that health equity has always been a major goal of the researchers here. My impression, Paul, is that this was very favorably reviewed during our last grant review.

 

PG:

Is there anything we’ve missed?

TL:

No, I think we’ve, in a half hour, got pretty far, covered a lot of material.

 

PG:

We certainly did. Well, thank you so much, and congratulations again.

TL:

And, Paul, congratulations to you on how you’ve evolved over the years. I remember when [The Cancer Letter] was the red-and-white banner, and it was paper, and it came in the mail, and now, you’ve really found a niche that’s made a huge difference in the cancer community.

 

PG:

Well, thank you. It’s a privilege to have this job, really.

TL:

It doesn’t mean I always agree with, you, though.

 

PG:

You shouldn’t, that’s wrong. Well, we’ll stay in touch on all of this.

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