Cancer immunotherapy has life-saving powers — and limits

For some patients, the body’s own natural immune system is being used to fight their cancer. Meet a woman who has lived years past her doctors’ prognosis, thanks to the emerging field of immunotherapy. Then Hari Sreenivasan discusses the promise and limits of the treatment with Matt Richtel of The New York Times and Jeff Bluestone, director of the UCSF Hormone Research Institute.

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    But first: the emerging field of immunotherapy, and its potential to help fight cancer in some patients.

    Hari Sreenivasan has a conversation about its promise and limits in a minute.

    We begin with the story of a cancer patient who was told at one point that she only had six months to live. She has now lived several years beyond that, thanks to her novel treatment. Those kind of treatments are the focus of our weekly segment, the Leading Edge.

  • MELINDA WELSH, Cancer Sufferer:

    My name is Melinda Welsh. I'm a writer, and was editor of The Sacramento News and Review for around 25 years.

    And when I was diagnosed with cancer, it just came naturally, I guess, to write about it. It was shocking to hear. I felt stunned.

    It is squamous cell carcinoma. And after we learned that the cancer had metastasized, we went to see some specialists. I asked each of them how much time I had left, and that's when they told me, you know, six to nine months, months to a year, a year-ish.

    You know, I started writing again, and I felt I had something to say that might mean something to other people because of the lessons I was learning facing death.

    "The enormity of the news didn't sink in fully, not at first, even after my doctor uttered the words, 'I'm sorry, we did find cancer.' I have turned my attention to the question, how do I best spend the time that I have left? My answer is writing, family and friends, the pleasures of small things. I was told, don't skip dessert, so we don't. We have taken to getting up a few early mornings a week and driving out to see the sunrise over the flatlands of our mostly rural county."

    I can't believe this. It is going to be a great day.

    "I will take solace in the idea that, once gone, I may come to occupy a small space in the hearts of the people who loved me most, and perhaps from there, I will be the source of a few simple reminders: Time is limited, life is miraculous, and we are beautiful."

    I always loved my life. I felt very lucky, my meeting up with Dave, my love of my life, best friend. So, having cancer, it just made me want my life, but more so.

    After that first piece was published, we had a breakthrough. I started immunotherapy. And Dr. Algazi, who is our — my oncologist, surprises us by showing up in the infusion room. And he says, "I just talked to the radiologist. The neck tumor has vanished. And so have the other tumors."

  • DR. ALAIN ALGAZI, Skin Cancer Specialist:

    My name is Alain Algazi. I'm an oncologist.

    I specialize in head, neck cancer, and melanoma. I work at the University of California, San Francisco. Melinda presented with squamous cell cancer in a lymph node. It was metastatic, but she was diagnosed at a time when we had access to several new drugs. And those drugs turn the immune cells back on that are in the tumor, and allow them to fight more effectively against the cancer.

    So, basically, they're taking your native immune response and enhancing it. So, we caused the tumors to regress and go away.


    I think it actually took a day or two to fully sink in that my calendar had expanded. Instead of the coming demise that we expected, I was feeling fine, and the cancer was retreating.

    So, on the anniversary of all the doctors giving me a year to live, it was time to write part two.

    "In the weeks that followed my public coming out about the grim news, a benevolent tidal wave of comments and e-mails washed over me from friends, co-workers and many thousands of strangers. Now when I run into friends on the streets of my town, they hug me and tell me I look great. But I can see it in their eyes; what they really want to say is, aren't you dead yet?

    "Well, no. As it turns out, I became a terminal cancer patient at a time of sea change in research on the disease. What changed? Immunotherapy, a new set of medicines that help patients like me use our bodies' natural defenses to fight cancer."


    Basically, there are brake pedals on immune cells, so when you turn off the brake pedal, you allow the immune system to function, you allow it to fight. But I think the cancer is always there, and it's a battle between the immune system and the cancer.


    "Nobody knows how long the good news will last for me or other cancer patients who are responding to immunotherapy. Like me they probably feel a miraculous gift — unanticipated time of unknown duration — has been dropped into their laps."


    It's like working for NASA in the 1960s. You know, can you imagine? That sense of discovery, that sense that you're changing the world, or at least there while the world is changing, and you're able to really help.


    Unfortunately, many people have cancers that there's no immunotherapy for, they can't get access to trials. The drugs are very expensive. Also, a lot of people who do qualify for immunotherapy simply don't respond.


    Melinda is, in a sense, an example of both the potential and the limitation.

    We have seen so much progress with her with immune therapy. But the cancer didn't go away.

    What we're trying to do is increase the chances that you're going to stay in remission indefinitely.

    A few years ago, she wouldn't survive. Now she might survive. We don't know what's going to happen for certain, but there's this enormous potential.


    We don't want to hope for too much. We don't want to go into denial that I have got this deadly disease that's trying to kill me. I do. But I'm making milestones that I didn't think I would make.

    I didn't think I would be alive to reach my 60th birthday. I didn't think I would make it to my 35th wedding anniversary, which is coming in April, and I'm assuming I will still be here.

    I want to live fully in the present. At the same time, just a little bit of future is awfully wonderful mixed in with that.


    People come to me, and they have low expectations. People think, I'm going to die. And my thought is, it doesn't have to be that way. We have now ways of keeping people well, not just for a few months, but for potentially years. So this is a time of hope.


    "I am still coming to terms as best I can with my own unequivocal transience. But, no, I'm not dead yet. When people are surprised to see me, I tell them I'm among the early fortunate. Facing death on a close horizon has heightened my awareness that our time on Earth is finite. But quite unexpectedly, it has also made me a living, breathing advertisement for humanity's hopeful new edge on cancer."


    That was Melinda Welsh with her story.

    Let's get a broader look at what these treatments may offer and their limits.

    Jeffrey Bluestone is a leading researcher in this field. He is the president and CEO of the Parker Institute for Cancer Immunotherapy. He's also a professor of metabolism and endocrinology at the University of California, San Francisco, School of Medicine. And Matt Richtel is a science writer who has covered this extensively for The New York Times.

    Mr. Bluestone, I want to start with you before all of our viewers start to call their oncologists if they're facing this. This is still not quite at the phase where we're seeing it effective in, say, lung cancer, and prostate cancer, and breast cancer and the major cancers that so many people face.

    JEFFREY BLUESTONE, CEO, Parker Institute for Cancer Immunotherapy: Well, actually, we have made a tremendous amount of progress, for instance, in lung cancer.

    These so-called immune drugs, these checkpoint inhibiters, are now treating a lot of non-small cell lung cancers with great success, in 30 to 40 to 50 percent response rate, so very high, as in melanoma, as in some head and neck cancer.

    Yes, there are a lot of cancers we still have a long ways to go, but in some of the cancers you mentioned, we have actually made tremendous progress.


    That's great to hear.

    Matt Richtel, you have covered this. You have chronicled people who have fought through their cancers, had this sort of immunotherapy work, and also some who haven't. What are some of the shortcomings or limitations?

  • MATT RICHTEL, The New York Times:


    First of all, that was a marvelous piece that captured just how remarkable this science is on the very edge of life and death.

    And you have asked a great question. And the answer is the very thing that makes this therapy so potentially powerful or powerful also causes some challenges. And that is this. When you soup up or unleash the immune system, you have an opportunity to have it attack healthy organs, healthy cells.

    And so sometimes you see very challenging stories where a cancer — a tumor will disappear, but the person will become sick with the equivalent of an autoimmune disorder. And, in fact, we have with Dr. Bluestone just an amazing authority to probably elaborate on that.


    Mr. Bluestone, go ahead.


    Yes. So, I think that what Matt said is absolutely true.

    The immune system is an incredibly powerful force. It's designed to recognize everything that is foreign. And in the process of doing that, and when you unleash it the way these new drugs do, you can often, not that often, rare compared to the response rate get these autoimmune diseases.

    At UCSF, we have had several cases in the last couple years of patients who developed type 1 diabetes, an autoimmune disease that causes the destruction of your insulin-producing cells. And trying to understand how to control these side effects is one of the key areas for the Parker Institute, at UCSF as well.

    And so the goal here is to have this unleashing of the immune system, which is key to eliminating the cancer, while moderating this unwanted attack on your own tissues.


    Matt Richtel, with all of the different scientists that you have spoken to, where are we in this arc? Some of the people who have been profiled in your story say this is almost like where NASA engineers were in the '60s.


    Yes. I love that comparison, and I have heard various ones along the same lines.

    I can't tell you how wide the breadth of potential is. It's somewhere on the continuum from, you know, marvel of science to change the world. Here's what I mean, and then I will answer your question directly.

    Absolutely, we are seeing at least a marvel of science, in that people who were not previously savable from cancer are being saved. That alone is marvelous.

    On the change-the-world end of the continuum, we're certainly not there yet, but the potential exists to attack one of the biggest killers in the world. We have done away with a lot of the low-hanging fruit of what kills us through things like antibiotics. So now cancer, which many people never survived to even get, is the second leading killer in this country.

    It could change the world if this hangs on. Why are we just still at the beginnings of that? Because, as Jeff — as Dr. Bluestone underscored and as lots of scientists have told me at this point, we can't yet tell if more people will either suffer side effects or relapse ultimately than we know of now. And it's so early on that we just can't answer that question and we probably won't be able to for a decade or so.


    Jeffrey Bluestone, is that about the right timeline? There are still those hurdles, as we heard in the piece, that the drugs are still expensive, that there are still lots of nonresponsive patients.

    And then, as you mentioned, how do you calibrate the immune system per patient, so that it doesn't kind of go overboard and attack what we need to survive?


    Yes, we're certainly at absolutely the change inflection point.

    The world has changed for cancer therapy with immunotherapy. It's hard to even explain how different this approach is. Instead of using poisons to kill cancer or to wipe out the cancer cell, we're actually using our own body to do this.

    So, in this kind of transformational science, there's a lot to learn. We have to learn, what are the fundamental rules? And we have to learn how to moderate the drugs in a way that maximize the efficacy and minimize the toxicity.

    But I cannot imagine that, over the next 10 years, we don't start see a dramatic change in the long-term survival of many of the patients with many of the cancers. You have already seen it in melanoma. We have gone from 5 percent five-year survival to 40 percent five-year survival.

    We have seen it in certain lung cancers. So, yes, we're right at the beginning. But we're already seeing a dramatic change in a lot of these patients. And I believe this new science — and it truly is — bringing together the science of the immune system and immunology with the science of cancer in ways that we could never have believed we would be at, at this point.

    So, sure, I'm optimistic. I'm excited. I'm — every day I go to work, I just can't believe we're in this world we live in now.



    Could I just underscore something Dr. Bluestone said?

    You mentioned I have chronicled patients. One of them was a good high school friend named Jason Greenstein. And when Dr. Bluestone says treatments have changed, let me just tell you a quick anecdote that underscores how much.

    Over several years, this friend of mine, Jason, went through the traditional chemotherapy. And it ate him alive, just as chemotherapy can do, because you're giving someone toxins.

    Over the course of literally weeks when he took an immunotherapy drug, you could watch what was like a pumpkin-sized tumor in his back disappear by the day in picture after picture.

    And so that's the kind of quantum leap. Now, ultimately, he — my friend succumbed. But that's the kind of quantum change that Dr. Bluestone is describing.


    All right, Matt Richtel of The New York Times, Jeffrey Bluestone of UCSF and the Parker Institute, thanks so much.


    Thank you.


    Thank you.

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