Dr Jeffrey Zonder On The 5 Things Everyone Needs To Know About Cancer

An Interview With Savio P. Clemente

Breakthroughs can happen, so there’s always hope: Living to fight another day may very well mean you’ll have new weapons to fight with next time around. As I mentioned, cancer breakthroughs happen frequently and often they represent life-saving advances in our understanding of how to treat these diseases in a more targeted, more efficacious and less toxic manner.

Cancer is a horrible and terrifying disease. There is so much great information out there, but sometimes it is very difficult to filter out the noise. What causes cancer? Can it be prevented? How do you detect it? What are the odds of survival today? What are the different forms of cancer? What are the best treatments? And what is the best way to support someone impacted by cancer?

In this interview series called, “5 Things Everyone Needs To Know About Cancer” we are talking to experts about cancer such as oncologists, researchers, and medical directors to address these questions. As a part of this interview series, I had the pleasure of interviewing Jeffrey Zonder, MD.

Jeffrey Zonder, MD, is the leader of the Multiple Myeloma and Amyloidosis Multidisciplinary Team at Karmanos Cancer Institute in Detroit, and a professor in the Department of Oncology at Wayne State University School of Medicine. Dr. Zonder is an internationally known researcher who has contributed to the development of new drugs and drug combinations for treatment of patients with plasma cell diseases, including myeloma, AL Amyloidosis, light chain deposition disease and monoclonal gammopathy of undetermined significance (MGUS). Dr. Zonder was the principal investigator of a clinical study that helped establish lenalidomide as initial therapy for myeloma.

Thank you so much for joining us in this interview series! Before we dive into the main focus of our interview, our readers would love to “get to know you” a bit better. Can you tell us a bit about your childhood backstory?

I wanted to be a physician for as long as I can remember. As a kid, I was interested in the human body and biology, so science was always something on my mind. Later, my mother was diagnosed with lung cancer at a young age, and almost nothing about it made sense to me. She was a nonsmoker, which made her situation unusual. Her disease followed a really protracted course that defied everything every physician told her to expect, even after it was clear the cancer was metastatic. There was something different about her cancer, and though I had already decided I wanted to be a physician, I think that influenced me to pursue oncology and cancer research.

At the time, her doctors didn’t have the tools to do the kind of in-depth molecular profiling that we would routinely do now. There’s no way to know for sure, but it probably would have been beneficial in the selection of her treatment. Instead of relying on the broad shotgun-style lung cancer treatments available at the time, it may have been possible to target the precise molecular abnormalities that made her cancer behave so unusually. Now we routinely do that profiling with cancer patients.

What or who inspired you to pursue your career? We’d love to hear the story.

I was fascinated by cell biology in college and medical school. It always seemed to me that oncology was among the specialties where basic science knowledge could be most readily applied. My mother was diagnosed when I was in medical school, and then she had a long remission and relapsed when I was in residency, so my mother’s cancer diagnosis and her subsequent treatment were playing out right at the moment when I was considering my career path.

There was also a fantastic month-long outpatient oncology rotation that impacted my career choice. It was a masterclass in how to talk to patients, and more importantly, to listen to them. The way the oncologists connected with their patients, and the lengths to which the office staff would go to help their patients was a revelation to me, and it was a fundamental month in my training.

Suppose all your exposure to oncology during medical training is at the inpatient level, where you’re seeing the sickest patients with the worst outcomes. In that case, it’s easy to develop a negative impression about a career in oncology. My experience helped me to see things differently.

This is not easy work. What is your primary motivation and drive behind the work that you do?

The relationship between an oncologist and their patient is unique. I generally become involved in a patient’s care at the worst moment of their lives in terms of their health, and they’re desperately seeking guidance on how to manage their diagnosis.

Multiple myeloma is generally not considered curable, but therapies are improving and survival is improving steadily. The treatment is often complicated: the schedule can be rigorous and time consuming, side effects need to be recognized and managed, and assessing how well therapy is working is not always straightforward. Every time I see a patient, I have to evaluate the balance of risks and benefits, side effects and disease response, in order to best help a patient. I find that challenging and rewarding. It’s an opportunity to have a significant impact on someone’s life.

What are some of the most interesting or exciting projects you are working on now? How do you think that might help people?

In blood cancers, and really across many types of tumors, there is a broad class of new therapies, termed immunotherapy, that were not available a decade ago. A basic form of immune therapy is antibody therapy. Antibodies are targeted proteins that selectively bind to cancer cells to kill them. Sometimes, the act of binding the cancer cells can be toxic to them, or sometimes the antibodies deliver toxic therapy to the cancer cells. They’re a therapy delivery system at the cellular level. We’ve had antibody therapies for quite some time, but they were just the starting point. Immune therapies continue to advance. Now we have cellular therapies such as CAR T-cell therapies, which are incredibly effective one-time therapies that can result in persistent benefits because they’re essentially living therapies, tumor-targeting cells that survive and multiply after being infused into the patient.

These innovative therapies are a big focus of our research program at Karmanos Cancer Institute. Currently, these therapies provide options for patients who have failed standard treatments. However, in the future we will likely offer these therapies earlier in a patient’s cancer treatment, which could be more beneficial. We and others are conducting the clinical trials needed to demonstrate the safety and utility of these treatments compared to the current standard of care. So how does one define “better” than standard care? Better could mean the novel treatment is just as effective but less toxic, or maybe it’s less complicated with the same outcomes, or perhaps the novel treatment simply results in better outcomes. In the case of multiple myeloma, first- and second-line therapy is often extremely effective and can control the disease for years at a time. So to prove new therapies are better than that, you must clear a pretty high bar.

Well-designed large research studies are generally needed to bring new therapies to the clinic. For instance, the FDA recently approved a particular CAR T-cell therapy for multiple myeloma, and we anticipate others will soon follow. However, CAR T-cell therapy is currently only approved for use in multiple myeloma in cases where many other therapies have failed. As promising as CAR T-cell therapy seems for advance myeloma, we still aren’t sure whether it would be better than the therapies we currently use to treat earlier, less-resistant disease. Could CAR T-cell therapy be an alternative to stem cell transplant followed by maintenance therapy? Or would it be better to use CAR T-cells after a transplant as consolidation therapy, replacing maintenance therapy altogether? We don’t know the answer to these questions and many others, and only research trials will provide the answers.

For the benefit of our readers, can you briefly let us know why you are an authority about the topic of Cancer?

I’ve been in practice for 20 years and have focused on clinical and translational research for my entire career. I’ve benefited from good mentorship early on. Since I was a fellow at Karmanos Cancer Institute and Wayne State University, I have concentrated solely on multiple myeloma and amyloidosis for my entire career.

Karmanos Cancer Institute is a member institution of the Southwest Oncology Group, a National Cancer Institute-supported group of more than 4,000 cancer researchers that conducts clinical trials in adult cancers. We’re also a member of the Multiple Myeloma Research Consortium, a premier myeloma research collaborative. .

Personally, I’ve led national studies conducted through both organizations. We have the largest multiple myeloma and amyloidosis program in the state of Michigan here at Karmanos. We perform more than 100 stem cell transplants a year for just these two diseases, and we have a substantial clinical trial portfolio for all stages of multiple myeloma and amyloidosis.

Ok, thank you for all of that. Let’s now shift to the main focus of our interview. Let’s start with some basic definitions so that we are all on the same page. What is exactly cancer? What causes cancer?

Cancer, at its most basic, is a group of diseases in which some cells in a person’s body grow uncontrollably. The types of cancers are named for the part of the body or tissue type where they start.

What causes cancer sounds like a simple question, but the answer is complicated — a lot of things contribute to cancer risk, and different cancers have different risk factors. We know tobacco exposure is responsible for many cancers. Regular alcohol consumption contributes to certain kinds of cancer, particularly heavy use. Other risk factors for some types of cancer include inherited risk and acquired risks like previous infection by a virus called HPV that puts people at risk for gynecologic, oral or anal cancers. We also know there are certain cancer syndromes where a specific genetic mutation increases your risk. In other cancers, such as multiple myeloma, a specific gene that accounts for it has not been identified, but certain populations, such as African Americans, have twice the risk of contracting it than their Caucasian counterparts. This suggests there is at least some genetic component to risk. We and others have collaborated to perform genome analysis research to characterize this better.

What is the difference between the different forms of cancer?

We’re used to thinking about cancers according to the site where they developed. That’s even how we name them — kidney cancer, throat cancer. Or we categorize them as solid tumors vs. blood cancer. That’s another way to think about them. We can also classify them according to what they look like under the microscope: adenocarcinoma, small cell cancer, squamous cell cancer, etc. But more recently, we’re starting to think about cancers by noting either the presence or absence of particular molecular abnormalities, as I wish we had been able to when my mother was diagnosed.

As an example, tumors can be analyzed for a mutation in a specific gene called BRAF. Mutated BRAF is present in a high percentage of melanomas, or skin cancers. Targeted therapies that suppress cancer cells whose signaling is affected by mutated BRAF exist, so those therapies have now become part of melanoma therapy, and they have dramatically improved outcomes. But it’s different with multiple myeloma, where only about four percent of patients have BRAF mutations. Since only those few myeloma patients with mutated BRAF could respond to targeted inhibitors, it’s useful to think about a person’s myeloma as being either BRAF mutation positive or negative. It’s a paradigm shift that only came about since the time I finished my hematology-oncology training.

I know that the next few questions are huge topics, but we’d love to hear your thoughts regardless. How can cancer be prevented?

I think for the most common solid tumors (breast, colon, prostate, lung, gynecologic cancers, to name a few) screening and early detection are still the key. If these tumors are detected early, surgical intervention is often curative. Some screening tests find pre-cancerous lesions which can be addressed before cancer ever develops. In the case of colon cancer, when you find polyps, removing those often prevents cancer. Finding abnormal but not yet cancerous cells on a pap smear allows you to prevent that cancer. In contrast, mammograms aren’t preventing cancer, but they are detecting cancer at a stage where it’s most curable.

While therapies for nonresectable tumors are getting better, the best chance of cure is when tumors are surgically manageable. That is honestly the best way to prevent cancer: find it early.

How can one detect the main forms of cancer?

Routine screening. Some cancer screenings are well known and straightforward, like colonoscopies and mammograms. However, newer tests are available as well. For instance, high-resolution CT scans for patients at high-risk for lung cancer could be impactful. There are also tests like ColoGard, which screen for DNA markers that indicate the presence of colon cancer.

Cancer used to almost be a death sentence, but it seems that it has changed today. What are the odds of surviving cancer today?

In many areas it’s improving, and that has to do with our increasing understanding of cancer and cell biology. With the development of a few key classes of drugs for multiple myeloma, all of which were developed since 2000, the median survival has increased from about three years to 10 years for patients with standard-risk features. I have an increasing number of patients 15–20 years into their cancer journey who are doing relatively well. That said, most of these patients are on therapy for the rest of their lives after diagnosis, and long treatment-free breaks are not typical. Further, there’s still a subset of high-risk patients who do not benefit from therapies to the same degree as other patients. With those subsets of difficult-to-treat patients, we still need those breakthroughs.

Can you share some of the new cutting-edge treatments for cancer that have recently emerged? What new cancer treatment innovations are you most excited to see come to fruition in the near future?

One group of new therapies is bispecific antibodies, which are antibodies that bind two cells instead of one. First, they can bind directly to the cancer cell, and second, they can bind to an immune cell, which physically brings the immune system into contact with the cancer cells. There is a growing array of bispecific antibodies being developed to bind to several different proteins on myeloma cells that we didn’t previously recognize as therapeutic targets.

Healing usually takes place between doctor visits. What have you found to be most beneficial to assist a patient to heal?

“Precision Medicine” should not only be focused on the molecular features of the cancer, but also, the person in whom that cancer is occurring. When I was in residency, the institution I trained at was known for teaching biopsychosocial medicine, which can be described as a holistic practice of medicine to incorporate factors outside the biological processes of illness. We were taught not just to treat the disease but also the patient who has the disease to help ensure their cancer journey is as comfortable as possible, both physically and mentally.

From your experience, what are a few of the best ways to support a loved one, friend, or colleague who is impacted by cancer?

Friends, family and acquaintances need to understand a cancer diagnosis also comes with natural grieving for the diagnosed person. That person sometimes faces immediate losses in terms of independence, stamina, employment, and financial security. Those are real losses that are sometimes almost unbearable for patients.

On top of that, there is grief associated with the perceived loss of anticipated things in your life — things you always took for granted would happen, like grandkids, a happy retirement, or your dream house. Suddenly those things may not seem attainable anymore and people grieve differently. Sometimes it’s expressed in sadness, and sometimes it’s anger. Sometimes it’s withdrawal. Understanding these issues is a big challenge for friends and family but trying to do so is the best way to help. Realize that someone else might not react the way you would when receiving the same information. More concretely, ask directly what somebody needs. They may need a ride to receive treatment. They may need company. Or maybe they need help with a pet. Take the time to figure out what those things are.

What are a few of the biggest misconceptions and myths out there about fighting cancer that you would like to dispel?

The first is that all therapy is highly toxic to the patient. That’s just not the case in 2021. Targeted therapies are often far less toxic to the patient than treatments used in the past, while they are increasingly toxic to cancer cells. This is a major advancement. We’re also a lot better at managing side effects than we used to be.

The second thing I wish we could do away with is the sense of fatalism about noncurative therapy. Treatment that doesn’t necessarily cure you can still help greatly improve quality of life. The field is so fast-moving and progress is often sudden. Sometimes there’s a fundamental breakthrough therapy that changes everything. And that breakthrough may be just a few years away.

Thank you so much for all of that. Here is the main question of our interview. Based on your experiences and knowledge, what are your “5 Things Everyone Needs To Know About Cancer? Please share a story or example for each.

1. Cancer isn’t just a biological affliction: Precision medicine should take into account both disease and patient characteristics to optimize therapy. For example, I know a patient who has a form of aggressive thyroid cancer who was treated with the most accepted standard therapy and had many debilitating side effects from it. Then molecular profiling was done on the tumor, which unexpectedly showed a specific and targetable mutation that typically responds well to a completely different drug than what the patient was on. Now he’s on that, the tumor is responding, and he has fewer side effects. So, the right therapy not only had better tumor effects but also had less toxicity. Ten years ago, that therapy didn’t exist, and fifteen years ago we didn’t have the capacity to do the testing which found the key target in this case.
2. Prevention leads to the best outcomes: We’ve made huge advances in cancer treatments, in solid tumors particularly. But early detection, before cancer develops is more critical than any improvement in treatment. While surgery is an option, early detection is still the best time to cure it. Early detection and treatment may even turn out to be important for multiple myeloma, though surgery won’t be the key here. All patients who develop myeloma have a precancerous stage, called MGUS, which stands for monoclonal gammopathy of uncertain significance. MGUS is quite common and increasingly common with age. Many with it never develop anything, but some develop a more advanced condition called “smoldering multiple myeloma,” and then full-fledged multiple myeloma. For patients with sufficiently high risk of progressing from MGUS to myeloma, we’ve found we can delay this progression by treating it early using therapies previously reserved for symptomatic myeloma. There are also researchers exploring whether it may be possible that super-aggressive therapy for those patients could eradicate the problem before it acquires the molecular features that make it an actual cancer.
3. Progress is driven by research: Of all the patients in the United States diagnosed with cancer each year, a very small percentage choose to participate in clinical research. That needs to change to move progress in cancer therapy forward. We need to make sure people realize that ethically designed research will never result in a patient receiving therapy inferior to the current standard of care. Additionally, patients should understand that it’s highly likely there are relevant clinical trials available for your diagnosis, likely nearby if you live in a major metropolitan area. Your oncologist, a support group, or a disease-specific research foundation may be able to help you navigate this. For example, I will often direct a patient to the Amyloidosis Foundation or the Amyloidosis Research Consortium for help identifying a clinical trial nearby, or at the least to help patients connect with a physician or institution where a trial is available. Patients should always find out if clinical trials are an option.
4. Effective therapy, even if noncurative, can be extremely beneficial: As an example, I have a patient who was diagnosed with multiple myeloma, and he had difficult-to-manage complications right out of the gate. He was incredibly ill and at first we didn’t know if he would survive, but he did, and the therapy eventually brought his myeloma under control. He didn’t have a complete response, but his health improved dramatically. Since his recovery from the initial diagnosis and treatment, his grandchildren were born, and he hiked to Mount Everest Base Camp with me to raise money for multiple myeloma research. He’s still on therapy to control his disease, but he’s in a far different physical place than at the beginning. His disease is under control now and he’s had amazing life experiences since then.
5. Breakthroughs can happen, so there’s always hope: Living to fight another day may very well mean you’ll have new weapons to fight with next time around. As I mentioned, cancer breakthroughs happen frequently and often they represent life-saving advances in our understanding of how to treat these diseases in a more targeted, more efficacious and less toxic manner.

You are a person of great influence. If you could start a movement that would bring the most amount of good to the most amount of people, what would that be? You never know what your idea can trigger. :-)

My movement would be around supporting clinical research. I would focus not only on improved coordination of research to advance cancer treatment, but also on a careful examination of how research can be designed or messaged to encourage more patient participation. A much-needed increase in clinical research participation would move the field fastest. Is there any guarantee that a person who participates in a clinical trial will directly benefit from having been included? No. But in terms of impacting the most people in the future, the best way to help them is to find the best therapies fastest.

How can our readers further follow your work online?

I would be thrilled if readers would familiarize themselves with cancer research in general, clinical trials specifically, and if they’re interested in learning more about multiple myeloma and amyloidosis, my specialties, they can visit here.

Thank you so much for these insights! This was very inspirational, and we wish you continued success in your great work.

Thank you for interviewing me. It was a pleasure.