How COVID-19 is Impacting Care for Lung Cancer Patients May 7, 2020December 14, 2022 Arthur N. Brodsky, PhD As we grapple with the COVID-19 pandemic and search for solutions, we must all take care to protect ourselves as well as others in our communities, especially those who are at higher risk for severe disease. This is important for health care workers, who interact with high-risk groups of people, including cancer patients. While all cancer patients may need to discuss their specific risks associated with COVID-19, special consideration must be given to people with lung cancer, due to the respiratory nature of COVID-19, and blood cancers, which can affect the immune system’s ability to root out infections caused by this new coronavirus. To gain a better understanding of how this current situation is impacting clinical cancer care, especially for lung cancer patients, and how our health care system and physicians are adapting to meet the moment, we spoke with lung cancer expert Joshua K. Sabari, MD, of the Perlmutter Cancer Center at NYU Langone Health. In addition to treating patients in the clinic, Dr. Sabari also leads efforts to develop biomarker-driven clinical trials that offer patients unprecedented access to novel immunotherapies and personalized cancer treatments. Arthur N. Brodsky, PhD: Dr. Sabari, thank you for joining us today! Given that COVID-19 is a disease that primarily affects the lungs and cause acute respiratory severe disease, or ARDS (though we know how that it also can wreak havoc on other organs and systems), are people with lung cancer more susceptible to infection by the new SARS-CoV-2 coronavirus or developing serious disease as a result? Joshua K. Sabari, MD: From what we understand so far, patients with lung cancer do not appear to be more susceptible to acquiring the novel coronavirus. However, lung cancer patients do seem to have more symptoms and more complications from the virus if they do acquire it. This is likely due to underlying dysfunction in the lung that is primarily connected to smoking history. We know that smoking can suppress patients’ immune systems as well as lead to inflammation in the lungs, which seems to be a terrible setting in the presence of COVID-19. So, it’s not that patients with lung cancer are at increased risk of getting the virus, but rather it’s that, if they do get the virus, they’re at increased risk of developing complications and potentially serious illness. Now, patients who are already receiving cancer treatment, there are some data showing that patients who are on chemotherapy, right, so conventional cytotoxic chemotherapy, those patients are significantly or profoundly immune suppressed and they may have worse outcomes overall in relation to COVID-19 infection. Cancer patients receiving immunotherapy with checkpoint blockade also appear to have increased rates of complications from COVID-19 related inflammatory changes in the lung. So those patients do seem to have, again, not increased risk of acquiring the virus but increased complication rates primarily from pneumonia from the virus. Arthur N. Brodsky, PhD: With respect to the increased risks associated with smoking, is that for people who currently smoke or former smokers? What about people who recently quit? Joshua K. Sabari, MD: That’s a great question. We know that active smokers are at the highest risk, but even patients who have quit recently—within the last six, eight, or twelve weeks—whose lungs may still be experiencing smoking-related inflammation may be at increased risk. Now, we don’t think that somebody who has quit smoking five, ten, fifteen years ago is at increased risk of acquiring coronavirus, but they should still be cautious about their risks for developing lung cancer. Arthur N. Brodsky, PhD: Now, as you well know, even amid this pandemic, cancer hasn’t stopped. It’s still affecting and changing people’s lives every day. At the same time, have the current circumstances altered how you provide care for people with cancer? Joshua K. Sabari, MD: I’ve been on the coronavirus wards over the last two weeks and our team has diagnosed three new patients with lung cancer in the hospital, so we’re still seeing newly diagnosed patients with lung cancer. The problem is I don’t think these patients are getting to see the right doctor at the right moment because of how resources are being allocated during the pandemic. There has been a tremendous reduction in early screening with low dose CT scans. Typically, patients are referred to medical oncology by primary care and or pulmonary physicians. However, given the pandemic patients are presenting to medical attention quite late in their disease course. The three patients that I mentioned unfortunately also have COVID-19, which will complicate their workup and treatment plan. The patients who are being diagnosed at the moment are a unique population that we don’t really have much clinical experience with. There are patients who are recently diagnosed or recently started therapy who come into the cancer center for their treatment. We’re having discussions with them about the risk-benefit of getting treatment. So if someone has a curable disease like a stage three lung cancer, we treat with the intent to cure them, and this can be done without needing to go into the hospital because most of these things can be done in the cancer center. We’ve also tried to move most of our visits remotely, if possible. Now, it’s difficult to give infusions remotely but all the follow-ups, the toxicity labs, we’ve been doing that all remotely via telehealth, which has worked out very well. Arthur N. Brodsky, PhD: Have you had any situations where treatment either needed to be postponed or put off altogether? Joshua K. Sabari, MD: Yes, primarily for those with metastatic disease. If somebody has been stable on immunotherapy for a while, for example, we are delaying some treatments, because we don’t know the risks of immunotherapy in the COVID-19 era. For example, pneumonitis, or inflammation of the alveoli in the lungs, we normally would have thought that was caused by the immunotherapy. However, with COVID-19, we’re seeing patients, some of whom are asymptomatic, who have these dramatic changes in their scans, or show signs of neuropathy. Ultimately, every decision we make is made on a case-by-case basis. Whether over the phone or by video chat, we have those discussions about the risks and benefits with patients and their families, and then make a decision together. Additionally, in patients with stage two or stage three disease, where we can potentially cure them, we have a discussion, but I usually recommend continuing therapy because stopping treatment might change their outcome. Arthur N. Brodsky, PhD: It sounds like a very challenging situation. Amid this uncertainty, the patient-doctor relationship would seem to be more important than ever. And yet, you can’t physically meet as you normally would, so how do you work to maintain optimal relationships with your patients? What have you learned about how to make the most of these digital check-ins? Joshua K. Sabari, MD: If you’d asked me this question a month ago, I would tell you I don’t know much about telehealth or telemedicine. But communication and building a healing relationship is critical no matter what. Even before this pandemic, I gave all my patients my cell phone number. They’re always told to call, to reach out with everything. It has been difficult not being able to sit down in the room with patients and family members. What I’ve tried to do with the telehealth and telemedicine consultations is to keep it like we would have a regular visit in the office. Talking about how they’re feeling, how they’re doing. I always try to involve a family member, a friend to get another frame of reference and more insight. The trickiest part, especially for patients who are not as tech savvy, has been getting on and figuring out how it works. How to get back in if we get disconnected, etc. Overall, though, the telehealth visits have worked out very nicely in the sense that patients have been able to see me and I’ve been able to see them. Unfortunately, I can’t touch them, can’t examine them physically, but it is very helpful to see how people are doing. Based on a few of the telehealth visits I’ve had, I have brought some patients into the office to further assess them, to get labs and to check pressure, but most of the digital visits that we’ve had have been very successful in the sense that we are able to continue the treatment relationship. Arthur N. Brodsky, PhD: That’s great to hear. It sounds like you’re doing your best to limit the in-person interactions to only the things that are absolutely necessary. Joshua K. Sabari, MD: Yes, we’re trying to protect patients. We’re also trying to protect ourselves and other people here in the cancer center. That being said, everybody coming into the cancer center is getting their temperature checked, they’re getting asked questions like whether they have any fever, sick contacts, cough. There’s a whole list, and patients are being triaged and looked at in different ways based on their answers to certain questions. All that being said, I think it’s best to keep somebody at home if they don’t need to be here in the cancer center. Arthur N. Brodsky, PhD: Absolutely. Now, I want to dive deeper into what we know so far about COVID-19 and why it’s so deadly. One reason appears to be that it causes a phenomenon called cytokine release syndrome, or cytokine storm, which has been associated with deaths caused by the disease. This excessive immune behavior has been observed in blood cancer patients, both those who receive bone marrow transplants as well as those treated with a newer form of immunotherapy called CAR T cells. Have we learned anything about cytokine storm in the context of cancer that could potentially help how we address COVID-19? Joshua K. Sabari, MD: The novel coronavirus has been challenging in the sense that some patients test positive who are barely symptomatic, who maybe have a cough or low-grade fever. Then you have a sort of opposite extreme where patients about a week into their illness seem to develop respiratory failure. They can’t breathe and get oxygen. We don’t really understand why it affects people differently, but we do think that it’s likely related to an immune response or cytokine storm type of response. Our blood cancer colleagues, especially those familiar with CAR T cells, have been helpful here, thanks to their experience treating cytokine storms. From what we’ve seen previously with CAR T cells, the pro-inflammatory marker interleukin-6 (IL-6) appears to be one of the key cytokines leading this inflammatory storm. We hypothesize that in COVID-19 pneumonia, this may lead to increased dysfunction that disrupts gas exchange at the capillary blood vessels that normally take up oxygen. We have a drug, tocilizumab, that blocks the IL-6 receptor and has been FDA-approved for rheumatoid arthritis. More recently, we’ve been using it frequently in cytokine release syndrome associated with CAR T cells. During the current crisis, we have been using this in our patients who are critically ill, along with other antiviral therapies and other anti-inflammatory therapies. I’ve seen a handful of patients now treated with this in in-patient ICU type settings, and we have seen a reduction in IL-6. Now, we don’t yet have great aggregate data to support whether this is a clinical strategy moving forward. We have prospective studies that are going on now looking at that, but from my handful of experiences, it does seem to have some clinical benefit for our patients. I think early intervention and early use of the drug seems to be more useful than waiting until later or until it’s too late. Arthur N. Brodsky, PhD: It’s relieving to hear that, in some ways, we’ve been able to get a jump on this particular aspect of the problem because we’ve encountered it before. Ideally, we’d like to have a vaccine that could prevent infection in people in the first place, and one of the vaccines that’s being tested right now against the novel coronavirus is an mRNA vaccine. As part of a Cancer Research Institute (CRI)-funded clinical trial, you’re using the same mRNA vaccine strategy—albeit one that targets different molecules—and using it to treat patients with advanced lung cancer. Could you talk a little bit about how these types of vaccines work and how this approach might be helpful against COVID-19? Joshua K. Sabari, MD: Vaccines made from mRNA, or messenger RNA, have been extremely exciting and novel area in cancer, but obviously also in the infectious disease arena, particularly with viral illnesses. There are two types of mRNA vaccines. One is an off-the-shelf vaccine where you basically identify an antigen or something unique to a cancer or a virus and then you build a vaccine in order to illicit an immune response to that antigen. So the mRNA vaccine that we’re working on in collaboration with CRI and Ludwig Cancer Research is an off-the-shelf vaccine that enables the immune system to target six antigens that are uniquely expressed in lung cancers. With this vaccine, we’ve seen very impressive results in combination with checkpoint immunotherapies targeting the PD-1/PD-L1 and CTLA-4 pathways. Using that idea and the same technology that we use in cancer, we can apply it to the infectious disease arena. Many companies are now working on developing mRNA-based vaccines specific for the novel coronavirus. The problem is that it’s going to take time. It’s not something that we’re going see in the next three or six months. I think this is going to take at least a year or longer. We also know that there are different strains of the virus and this virus is likely mutating over time, so it’s going to be important not to jump the gun here. We need very, very robust pre-clinical work before these vaccines enter human patients. I do have hope though, and I do think that we will be able to develop a vaccine in the next twelve to twenty-four months, because this is not a problem that’s going to go away without a more strategic approach. Arthur N. Brodsky, PhD: I share your optimism. It’s a promising strategy, but it definitely needs to be done the right way, which takes time. From the public’s point of view, it might be hard to understand why this process seems to take so long. Joshua K. Sabari, MD: We all want to be hopeful and we are going to rise above this together as a community, as a world. But I think it’s critically important for everyone, including in the field of science, really to respect each other and to really take each other’s views at face value and not jump to conclusions. And that’s really the beauty of science, right. Things are not fast and easy. Things are hard and they take time, but because of our urgent need for treatments, some people are sort of overlooking this process that is science. It takes time and a lot of effort to develop new therapies for our patients, to make sure they’re both safe and effective. Arthur N. Brodsky, PhD: Absolutely. Earlier, you alluded to working on the COVID ward and how everyone in the hospital is going above and beyond at this moment. What kind of impact has this had on your research, and specifically how has it affected clinical trials? Joshua K. Sabari, MD: We are no longer subspecialists. I no longer view myself as only a thoracic medical oncologist. We’re all COVID physicians, right? I got an email, probably about three or four weeks ago now, congratulating me that I was promoted to a hospitalist and I was a little bit shaken. But then when I looked at the email, I saw that I was on it with graduating fellows, orthopedic surgeons, neurologists, everyone across the board. We have all come together and we still are coming together on a day-to-day basis when we’re taking care of patients who are sick. That’s why we all go into medicine to begin with. From a research standpoint, most of our clinical trials have been put on hold for the moment. We have not been enrolling new patients onto studies. Patients who are already on studies already will continue to be supported. The sponsors, the pharmaceutical companies have been phenomenal. The FDA has been phenomenal and granting lots of different exceptions and allowing patients to either get scans or toxicity bloodwork done locally, preventing patients from having to come into New York City. And again, we’ve done a lot of telehealth for patients that are currently on clinical trials. For some of our studies, we have very high objective response rates and the treatments have a high probability of impacting and improving a patient’s quality of life and overall survival. So in these cases, we really hope to get these drugs back to patients shortly because for the moment, our real focus has been in-patient treatment for people with COVID-19. One last thing I want to say is that, in general, keeping our cool is going to be critical here in our current situation. There’s a lot of hype. There’s a lot of excitement and fear. There’s a lot of false information. If you have a question about a symptom that you’re experiencing, please reach out to your doctor. Please reach out to your health care team. We’ve been dealing with this virus for the last month and a half now. We’ve learned a lot about it. We still don’t know close to everything, but I think as a community, as we continue to work together, we’re definitely going to get ahead of this. In the meantime, it will be important to keep a cool head and stay indoors. It’s critical that you not go out and do any non-essential activities outside the home. For my patients who have cancer, we’re here for you during this difficult time. If you’re not able to come into the office, that’s okay. We can talk on the phone, we can talk through video. It’s important that we keep this therapeutic relationship open and that you have hope that we are able to treat your disease and we are able to hopefully extend life with good quality of life. Impact of COVID-19 Pandemic on Global Oncology Clinical Trials Arthur N. Brodsky, PhD: Thank you so much, Dr. Sabari, for taking the time to speak with us today and, more importantly, for the invaluable work that you and your colleagues continue to do each and every day. Stay safe! Learn about immunotherapy for lung cancer Read more: Post navigation Analytical Strategies in Immunology for Cancer and COVID-19 with Dr. Katie Campbell Read Story How COVID-19 is Impacting Care for Blood Cancer Patients Read Story