What Diversity, Equity, and Inclusion Mean for the Health Sciences, and Why Big Data Needs Them All

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What Diversity, Equity, and Inclusion Mean for the Health Sciences, and Why Big Data Needs Them All

M.P.H., Ph.D., M.D., Professor of Biostatistics and Epidemiology, UCSF School of Medicine

M.D., Editor in Chief, Cancer Commons; Editor at Large, Medscape; Clinical Professor of Pathology, Northwestern University; President and Chair, The Lundberg Institute

Chair, Humanities Forum

Sometimes, because of the current political pushback, one can get the false impression that the academic attention that has recently been paid to increasing a university’s diversity, equity and inclusion profile is a new phenomenon—one that developed after the civil rights gains of minorities and women in the 1950s-70s. But the idea that people with different backgrounds, experiences, and viewpoints would produce better work by engaging with each other was a core principle of the first modern research university—which was founded in Germany in 1810.

The health sciences are especially dependent on accurate data, and imaginative but reasoned analysis of that data, and both the accuracy of the data and the usefulness of its analysis are put at risk by pretending that diversity, equity and inclusion are harming universities, including medical research universities, rather than helping them. The known inaccuracies caused by a historical research emphasis on male health, and inappropriate applications of those conclusions to female health due to the lack of research data on women, are examples of the risks involved.

Join us to hear Dr. Robert Hiatt, whose central focus at UCSF has been on building a strong transdisciplinary research and training program in epidemiology, make the case for how scientifically harmful deemphasizing diversity could be, and how the emergence of Big Data will be derailed quickly if the data that it uses has been corrupted by political whims distorting its scientific objectivity.

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Organizer:
George Hammond
Notes:
In association with The Lundberg Institute and the Philip R Lee Institute for Health Policy Studies at the University of California, San Francisco (UCSF).

Using Real World Outcomes from “People Like Me” to Guide Cancer Treatment

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Robert Palmer, MBA, Founder and CEO, PotantiaMetrics, Inc.

M.D., Editor in Chief, Cancer Commons; Editor at Large, Medscape; Clinical Professor of Pathology, Northwestern University; President and Chair, The Lundberg Institute

One of the most powerful questions a cancer patient can ask is, “What worked for other people like me?” The company PotentiaMetrics gets to the heart of that question with Capire360, its externally validated survival analytics engine trained on 2.2 million real-world cancer cases, and Ardynn, its Personalized Shared Decision Making (PDSM) platform, with support delivered through independent certified patient advocates. Here, our Curious Dr. George asks Robert (Bobby) Palmer, MBA, founder and CEO of PotentiaMetrics, about how the 10-year-old company helps cancer patients, caregivers, and clinicians.

Curious Dr. George: In the cancer domain, PotentiaMetrics emphasizes real-world data layered onto the world’s academic literature, as well as individual oncologist opinions, all structured to provide patients with cancer outcome charts for various treatments from “people like me.” Patients can use these comparisons to guide evidence-informed, shared decision making, with individual guidance from certified navigators.

What features differentiate your products from other similar offerings?

‍Robert (Bobby) Palmer, MBA: The most important distinction is point of intervention. Every other oncology support platform operates after the treatment decision has already been made. Navigation programs, second-opinion services, care-management tools, and payer-utilization programs all see the patient after the treatment plan is set. By then, cost and care trajectory are mostly locked in. PotentiaMetrics operates before all of them, at the moment the decision forms. That is the only moment at which the trajectory can be meaningfully redirected.

Capire360, our survival analytics engine, is built on more than 2.2 million real-world cancer cases from 500 or more institutions, covering 15 solid tumor types representing approximately 90% of adult cancer diagnoses, with longitudinal follow-up of up to 20 years. The models are Cox proportional-hazards survival models: transparent, auditable, and clinically interpretable—not a black-box output. They were externally validated at Erasmus University Medical Center, one of the foremost centers in clinical prediction modeling. Comorbidity burden is measured using the ACE-27, a validated scoring instrument, producing survival estimates that reflect the actual patient in the room, rather than a patient in the context of a clinical trial. The output is a set of individualized survival curves across realistic treatment alternatives at the modality level. Not population averages; a comparison with “people like me.” Learn more at potentiametrics.com.

The second distinction is independence. Ardynn, our PSDM platform, is delivered exclusively through certified patient advocates independent of any hospital, cancer center, or treating team. While hospital navigation programs facilitate delivery of a care pathway, Ardynn advocates support a patient’s independent engagement in selecting a care pathway. A tool that routinely shows patients that less-aggressive treatment produces equivalent survival cannot maintain credibility if it originates inside an institution whose revenue depends on treatment delivery.

The third distinction is how the data is delivered. Ardynn advocates present survival information in absolute terms and natural frequencies rather than relative risks, because relative risk reductions cause patients to systematically overestimate treatment benefits. For any given patient, our PSDM approach begins with clinical practice guidelines from the National Comprehensive Cancer Network (NCCN), layers in Capire360 outcomes data stratified to that patient’s profile, elicits and documents the patient’s goals and quality of life priorities, and synthesizes all three into a PSDM Report shared with the clinical team before treatment discussions begin. The oncologist receives a patient who arrives prepared, with their questions organized and their values on record.

‍Curious Dr. George: How well is this approach working in 2026?

‍Robert (Bobby) Palmer, MBA: The outcomes are documented and consistent. Across an observational cohort of 76 patients and 11 cancer types, first-course treatment costs fell 40% following a full PSDM engagement, from $6.82 million in recommended treatment costs to $4.07 million for treatments actually received, with no clinically meaningful difference in five-year survival for any cancer type in the cohort. Average savings per patient were $34,000, a 15-to-1 return on investment to payers. Approximately 40% of patients chose less-aggressive treatment than originally recommended. This is not a lower standard of care. It is what consistently happens when patients have accurate personalized survival data and a structured opportunity to articulate what they value.

Patient experience mirrors the clinical outcomes. Our Net Promoter Score is +85, against a healthcare industry average of +40. More than 100 randomized trials confirm this pattern at scale: decision aids consistently increase values-concordant choices and reduce decisional conflict without increasing patient anxiety. One patient described the experience plainly: “Fear wanted to make the decision for me. Ardynn gave me my numbers, and for the first time, the choice actually felt like mine.”

Curious Dr. George: How may patients with cancer, their caregivers, physicians, and health systems best access and use your services?

Robert (Bobby) Palmer, MBA: PotentiaMetrics operates under a live, auto-renewing contract with Surest, a UnitedHealthcare (UHC) health plan, and a master service agreement with UnitedHealthcare, representing full legal, compliance, clinical, actuarial, and data security review by the largest health insurer in the United States.

For patients and caregivers: If your employer offers UnitedHealthcare or UHC Surest benefits, ask your benefits administrator whether Ardynn is available to you. If you are outside those networks, contact us directly via rpalmer@potentiametrics.com. We navigate access on a case-by-case basis and will not turn away a patient who needs this.

For oncologists and clinical teams: Ardynn does not compete with the treating physician. It prepares the patient to meet with the physician as a genuine partner. The one-page pre-visit PSDM Report can be read in under two minutes, attaches to the chart, and supports MIPS quality measure documentation. Conservative modeling suggests the prepared-patient visit recovers approximately 10 minutes per new patient encounter. No EHR integration and no IT infrastructure is required to begin.

For health systems and payers operating in value-based contracts: Ardynn operates at the only moment in the cancer-care episode where cost and trajectory can actually be redirected, before the treatments have been decided on. Every downstream program is cheaper to run when the treatment decision that precedes it was made well.

‍Robert (Bobby) Palmer can be reached at rpalmer@potentiametrics.com.

The Strong Helping Hand of Cancer Commons

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Unsha Bakker, MSN, RN, OCN, CBCN

M.D., Editor in Chief, Cancer Commons; Editor at Large, Medscape; Clinical Professor of Pathology, Northwestern University; President and Chair, The Lundberg Institute

Cancer is frequently accompanied by psychological distress and mental health challenges that are often neglected. Here, our Curious Dr. George asks Unsha Bakker, MSN, RN, OCN, CBCN, Cancer Commons Oncology Nurse Navigator for the Brain Cancer Support and Solutions Alliance (BCSSA), for her perspective on these issues—and how Cancer Commons can help.

Curious Dr. George: There is so much involved in comprehensive care of patients with cancer beyond strictly diagnostic and therapeutic modalities. Access to appropriate clinical care, deep insurance coverage, navigating a complicated care path, understanding options, overcoming systemic inequities, communicating effectively, and even securing necessary transportation come to mind. How can Cancer Commons help a patient with advanced cancer cope with all these challenges, including the often-present mental and emotional stresses?

‍Unsha Bakker, MSN, RN, OCN, CBCN: Roughly 30–40% of individuals diagnosed with cancer experience psychological distress and mental health challenges, with many more sharing that impact, including caregivers and loved ones. Beyond that already alarming prevalence, lived experiences often surpass what data and literature can minutely illustrate. Each patient’s race through the cancer-care continuum often occurs in a silo, as access to healthcare outcomes is highly predetermined by social determinants of health, finances, location, and access to support systems. The focus of a patient’s care typically starts with a race against rapidly dividing cancer cells, while mental health distress continues to escalate just as exponentially, but becomes bookmarked for later in the corner of the room.

Cancer Commons offers hope to fight this fate, and gives individuals a chance to stop drinking from the overwhelming firehose of cancer care information, at no cost. Whether someone contacts us as a primary resource or a final opinion, not one person is turned away from our services. Cancer Commons offers a warm hand to hold and a shoulder to lean on. Grounded by compassion, empathy, and true human touch, Cancer Commons’ mission is to provide emotional support during turbulent times, a plethora of resources, and treatment guidance that colors outside of the lines—in contrast to the traditional, black-and-white box of the healthcare landscape. Cancer Commons’ goal is to see someone as whole, beyond just a diagnosis, through a deep, meaningful, and holistic lens—not just as anonymous numbers lost in a sea of patients.

Over many years of speaking with patients, caregivers, and loved ones, I have heard many mention feeling debilitated—as though a rug had been pulled from underneath them, shifting them into a permanent survival mode. Unfortunately, despite the well-documented mental health effects of cancer, barriers associated with mental health care remain. These include but are not limited to financial toxicity, access, stigmas, lack of health care literacy, and even, simply, the time to quietly care for oneself while juggling the realities of life that cannot take a back seat.

At a time when showing up authentically can feel terrifying and life altering, Cancer Commons wishes to hold space for all patients’ experiences. Some patients come to us having been told to celebrate their next birthday as if it will be their last, or to feel grateful that they are in remission; while others may be entering hospice and may not even make it to their next life milestone, bucket-list experience, or cherished aspiration.

While individuals may experience guilt, shame, and vulnerability associated with speaking their truth, mental health support can simply start with validating and witnessing individuals in their pain, quietly listening to their feelings in moments that are raw and genuine.

Self-care is often the last stop on the road, while it often should be the first. Reminding individuals to take part in one-on-one guidance with us, connect with others who have experienced similar life changes, and keep in mind resources available to them can hopefully create a sense of belonging and community while improving mental health. Cancer Commons can be that soft landing, where patients can start untangling the strings that make the impossible possible, in a completely judgment-free environment.

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‍Unsha Bakker is Oncology Nurse Navigator for the Brain Cancer Support & Solutions Alliance (BCSSA), a collaboration between Cancer Commons, Head for the Cure, and the Musella Foundation For Brain Tumor Research & Information, Inc. She can be reached at oncology@cancercommons.org.‍

Seeking Patients with Advanced Cancer for a New Clinical Study

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Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Prajit Pillai, PhD MBA
Director of Clinical Sciences, Cancer Commons

Cancer Commons has launched a new clinical study that features drug sensitivity testing—laboratory testing of individual patients’ cancer cells to identify drugs that might work for them. Here, our Curious Dr. George asks Cancer Commons Director of Clinical Sciences Prajit Pillai, PhD, MBA, about the study.

Curious Dr. George: Every year, approximately 600,000 Americans with advanced cancer experience progression of their disease beyond the standards of curative care covered by clinical guidelines. Yet, these guidelines include only a minority of the hundreds of anti-cancer drugs that have been approved by the U.S. Food and Drug Administration (FDA) for marketing, sales, and use. Cancer Commons’ new study enables practicing physicians to include drug sensitivity testing in their choice of such FDA-approved drugs in clinical research. Patterned on the N-of-1 approach, which focuses on a single patient at a time, this is a bold and needed study of an already-available, inexpensive resource. Dr. Pillai, what is this study? How will it work? And how may patients with advanced cancer and their physicians participate?

‍Prajit Pillai, PhD, MBA: This Cancer Commons N-of-1 study is the first precision medicine study that aims to generate predictive accuracy of functional assays in selecting effective off-guideline treatments. Since the clinical evidence of these assays is severely limited, oncologists are reluctant to use them. This study will add to that body of clinical evidence, and if successful, accelerate the acceptance of these functional assays for treatment selection in clinical practice.

The U.S. National Comprehensive Cancer Network (NCCN) develops the guidelines you described for clinical practice in oncology. If an FDA-approved cancer drug is not recommended in the NCCN guidelines for a particular cancer type, that drug is considered “off-guideline” for that cancer. Off-guideline does not mean the drug has been proven ineffective for that cancer. It means there is no double-blinded, randomized, controlled clinical trial (or other definitive source of clinical validation) that has led the NCCN committee to include that drug in the NCCN guideline for that cancer. A drug may be very effective at treating patients with a particular cancer, but if no clinical trial has been undertaken, then that drug will remain off-guideline for that cancer.

Medical oncologists are extremely reluctant to prescribe their patients off-guideline drugs. A recent study of the Flatiron database of 165,912 cancer patients showed that only 4.4% (1 in 23) received off-guideline drugs. Therefore, a method of guiding oncologists to promising off-guideline drugs, particularly for their advanced cancer patients who are out of treatment options under the NCCN guidelines, could potentially extend the lives of those patients.

In the precision medicine approach to cancer treatment, recommended therapies are selected by matching to a patient’s individual tumor profile. While genomic tests enable selection of targeted therapy, they cannot predict effectiveness of the therapy and have benefited less than 10% of cancer patients. Furthermore, practical challenges with integrating biomarker testing into clinical practice have resulted in most patients not benefiting from precision medicine.

To bring the benefits of precision medicine to more cancer patients, one practical approach is functional precision medicine (FPM), which integrates genomic tumor profiling with drug sensitivity testing (DST). FPM can both validate the genomic-matched findings as well as identify off-guideline drugs when targeted therapy is not feasible. Thus, FPM has the potential to guide oncologists to prescribe patient-specific, off-guideline drugs to advanced cancer patients who are out of treatment options under the NCCN guidelines, potentially extending their lives.

The Cancer Commons study will calculate the predictive accuracy of multiple functional assays (genomic and/or DST) to identify the tests that can be most helpful to patients, and to quantify the potential benefits of these tests.

The study will include 300 advanced cancer patients. The primary objective is to determine the predictive accuracy of selecting off-guideline drugs for advanced cancer patients based on ex vivo DST and genomic profiling. The secondary objective is to compare individual outcomes (response and disease-free survival) in patients treated with DST-guided therapy as compared to non-DST guided (conventional) therapy.

To learn more about the study and how to enroll, I encourage patients and their physicians to visit the Cancer Commons study page and the official study page at ClinicalTrials.gov. Other useful resources related to the study are available on our site for patients, oncologists, and patient navigators.

Dr. Pillai can be reached at prajit.pillai@cancercommons.org. 

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Morning Administration of Cancer Immunotherapy May Help Patients Live Twice as Long

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Cancer Commons Scientist
Amanda Nottke, PhD

M.D., Editor in Chief, Cancer Commons; Editor at Large, Medscape; Clinical Professor of Pathology, Northwestern University; President and Chair, The Lundberg Institute

Could boosting the benefits of immunotherapy for cancer patients be as simple as scheduling it earlier in the day? Here, our Curious Dr. George asks Cancer Commons Scientist Amanda Nottke, PhD, about the latest insights into this compelling question.

Curious Dr. George: Immunotherapy is a unique modality in that it stimulates the body’s immune system to attack the cancer. Circadian rhythms affect many biological systems, including the immune system. Given this, what do we know about how immunotherapy treatment timing relates to its efficacy?

Amanda Nottke, PhD: There is compelling evidence that cancer immunotherapy may work significantly better when given earlier in the day. This has major implications for clinical care as it indicates an easy, safe, and highly beneficial adjustment to treatment plans.

A few years back, clinicians noted something very interesting: people who usually got their immunotherapy treatment in the morning seemed to have a much better anti-cancer response and lived longer than people who usually got their treatment later in the day. It was striking, but perhaps not that surprising as it has long been known that the human immune system is affected by time-of-day, with increased immune activation in the mornings. However, an initial observation in the clinic is only the starting point; it is critical to further test and validate with appropriate research studies.

Fortunately, lots of data already exists from real-world patient experiences. Any time a person receives their immunotherapy and their outcome is recorded, researchers can look back to test hypotheses about things that may be improving (or worsening) those outcomes. These are called retrospective studies, and multiple of these can be combined into a statistically more powerful meta-analysis.

In 2024, a meta-analysis was done that combined the data from 13 different retrospective studies including 1,663 patients with metastatic non-small cell lung cancer, melanoma, kidney, bladder, or esophageal cancers. These participants had all received PD1/PDL1 immunotherapies (e.g., Opdivo, Keytruda), and some also received CTLA4 immunotherapy (e.g., Yervoy). This study found that on average, the earlier-time-of-day group lived twice as long as compared to the later-time-of-day group. For context, this is a significant and impressive effect, as the U.S. Food and Drug Administration (FDA) has approved cancer treatments with much weaker improvements over standard of care.

With this study, there is some challenge in interpretation because the 13 studies included in the analysis used different definitions of “early” versus “late” for their cut-offs. For example, one study defined “early” as receiving 25% or more of the total treatments before 1pm, whereas another study defined “early” as receiving 80% or more of the total treatments before 4pm. While the effect of “early” being associated with better outcomes is clear, based on this study it is hard to make any specific recommendation on how early is early enough, and what percentage of treatments should be at or before this time. Because none of the studies required all treatments to be in the morning, it is also undetermined what the true effect size is of morning administration—it could be even more significant!

While this is very promising, there are important caveats to consider with retrospective studies. Because these studies are not planned in advance to make sure the two groups being compared are similar other than the time of day they got their immunotherapy, there may be differences (“confounders”) that impact the results independently of the variable we think we are testing. In this case, it could be that people who had their immunotherapies earlier in the day tended to have certain characteristics that also improved their likelihood of a good response (e.g., age, employment status, better overall health, etc.).

Looking ahead, the gold standard for evidence is a prospective clinical trial, where the study is planned ahead of time such that the two groups are similar in all ways other than a random assignment of either earlier or later immunotherapy treatment. Encouragingly, a prospective trial in metastatic non-small cell lung cancer has already reported very similar results to the meta-analysis, using a cut-off of all 4 initial treatments before 3pm. Combined with the meta-analysis findings, this strengthens our overall confidence in the effect. The caveat here is that this study is running at a single hospital in China, so ideally there are future studies across a broader population.

So, what do we confidently know at this point?

  • In studies of metastatic non-small cell lung, melanoma, kidney, bladder, and esophageal cancer, people who received most of their immunotherapy treatments earlier in the day had better outcomes (i.e., longer time before progression and longer lifespan) than people who had most of their treatments later in the day.

What don’t we yet know?

  • What time specifically to use for a cut-off, and what percentage of treatments should be before that time
  • If this effect holds for other cancer types
  • If this is also relevant for earlier-stage disease, e.g., pre- or post-surgery for resectable cancers where immunotherapies are used (one recent study in the adjuvant setting showed a more modest effect with reducing risk of progression)
  • If this effect would be true for other types of cancer immunotherapies (e.g., CAR-T, personalized vaccines)
  • If there are certain types of people who may be more or less responsive to this effect, e.g., certain ages, genders, etc.

We urge researchers to continue to explore these questions, and in the meantime make the following recommendation for patients and clinicians:

  • Given the strength of available evidence for earlier administration in certain metastatic cancer types (lung, melanoma, kidney, bladder, esophageal), and that there is no known or plausible risk or negative impact of morning scheduling regardless of cancer type, cancer patients who are receiving immunotherapies should consider requesting as many of their treatments as possible be scheduled in the mornings or early afternoon (before 3pm).

Dr. Nottke can be reached at Oncology@cancercommons.org.

How Would a Mayo Clinic Oncologist Manage His Own Mantle Cell Lymphoma?

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Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Javier Munoz, MD, MS, MBA
Program Director, Lymphoma; Co-Director, Cellular Therapy Program; Director, Cancer Center Trial Office—Mayo Clinic (Arizona)

Cancer patients often ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Mayo Clinic oncologist Javier Munoz, MD, MS, MBA, how he would handle his own diagnosis of mantle cell lymphoma. At the Mayo Clinic in Arizona, Dr. Munoz serves as Director of the Lymphoma Program, Co-Director of the Cellular Therapy Program, and Director of the Cancer Center Clinical Trials Office.

Curious Dr. George: Please consider this hypothetical scenario: You are a young male physician in general good health in an active practice of clinical oncology. You have recently experienced unintended weight loss of 15 pounds, loss of appetite, general malaise, and a low-grade fever with sweating at night. You consult your primary care physician who observes skin and mucous membrane pallor and palpable lymph nodes in your groin and axilla. She orders a complete blood count, which finds a hemoglobin of 11, a normal white blood cell count, mild thrombocytopenia, and relative lymphocytosis. Biopsy of an axillary lymph node results in the diagnosis of mantle cell lymphoma. How would you proceed?

Javier Munoz, MD, MS, MBA: Mantle cell lymphoma (MCL) is a rare disease with an ominous prognosis. If I were facing my own high-risk MCL, I would begin by acknowledging the shock. As oncologists, we often speak of probabilities and protocols, but when the disease becomes your own, those numbers carry a different weight. The first step would be to breathe, to process, and to gather the right team—a reminder that none of us, even physicians, should walk this path alone. High-risk disease may be defined by TP53 alterations, aggressive histological features like blastoid/pleomorphic morphology, or a high proliferation rate (e.g., Ki-67 index of 30% or greater). In this fictional case, my MCL is high-risk due to the presence of a TP53 mutation which historically heralds resistance to conventional chemotherapy agents.

After confirming pathology, morphology, and proliferation rate, I would seek enrollment in a clinical trial. MCL has long been considered incurable (outside of allogeneic stem cell transplantation), but that paradigm may soon be shifting with novel agents and cutting-edge clinical trials. The TRIANGLE and BOVen studies have introduced BTK inhibitors into the frontline management of this disease, suggesting that patients may avoid the toxicity of high-dose chemotherapy and autologous transplant. Knowing this, I would likely choose a chemo-free, novel-agent regimen rather than intensive chemotherapy for my own case of newly diagnosed TP53-mutated MCL. Outside of a clinical trial, I would choose for myself the triplet explored in the BOVen trial (zanubrutinib, obinutuzumab, and rituximab), which now appears in national cancer guidelines as an option for patients with TP53 mutations. Because of the TRIANGLE trial, I would personally shy away from accepting consolidation with autologous stem cell transplantation when achieving first complete remission in MCL.

I would continue to surround myself with positive, uplifting people and go through this journey day by day. If you have been diagnosed with cancer, there will be days that you will not know what the right way forward is. It is not a right or wrong situation, but rather what feels right to you. Find solace knowing that many have walked through this pathway before, and you do not have to walk alone. Regarding second or even third opinions, your doctor will never be upset, as we embrace collaboration and learning from you and our colleagues.

If my disease were to relapse, I would look toward CAR T-cell therapy, such as brexucabtagene autoleucel or lisocabtagene maraleucel—treatments that have yielded remarkable remissions for patients who once had no good options. CAR T-cells seem to be the great equalizers as they seem to work both for TP53-mutated and TP53 wild-type MCL. These therapies are not without risk—cytokine-release syndrome, infection, and neurologic side effects can be daunting—but I would be willing to endure the risks in exchange for the benefits of remission with a long-term horizon.

On a personal level, I imagine the greatest challenge would be relinquishing my instinct to analyze every data point and instead embracing the need to live fully in the moments between treatments. I would lean on my family, my colleagues, and my patients, whose courage has always reminded me that healing is as much about connection as it is about medicine.

For anyone newly diagnosed with MCL, my advice is simple: find a team you trust, seek second opinions, and ask about clinical trials. Revolutions in cancer care are built on hope—and in MCL, that revolution is happening right now with a quickly changing therapeutic paradigm. The future is indeed bright for MCL. By enrolling and believing in clinical trials, we can tailor such future together and ultimately cure MCL.

For publication questions, contact gdlundberg@gmail.com. For appointments with Dr. Munoz, contact ARZHEMONCNPS@mayo.edu.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

How Would a Mayo Clinic Oncologist Manage His Own Acute Lymphocytic Leukemia?

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Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Mark R. Litzow, MD Professor Emeritus, Mayo Clinic (Division of Hematology)

When facing a frightening new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks leukemia expert Mark R. Litzow, MD, how he would handle his own hypothetical cancer case. Dr. Litzow is Professor Emeritus in the Division of Hematology at the Mayo Clinic in Minnesota.

Curious Dr. George: Please consider this hypothetical scenario: You are an older white American male who has enjoyed good general health most of your life. Recently, while starting retirement, you have lost your appetite, developed a low-grade fever, and felt quite fatigued. And, for a few weeks you have accumulated more bruises than expected. Your primary care physician comments that you seem pale, and on examination, your spleen is palpable. A complete blood count (CBC) reveals pancytopenia with an elevated white blood cell count, and circulating blasts are visible on your blood smear. How would you proceed?

Mark R. Litzow, MD: To start, in real life, I am a 71-year-old retired hematologist. I had an NSTEMI (a type of heart attack) 2 years ago, with a 95% occlusion of my ramus intermedius artery that was successfully stented with a drug-eluting stent. I completed a year of dual anti-platelet therapy and now remain on low dose aspirin along with lisinopril and atorvastatin. Today, I remain symptom-free and am physically active, having completed a half-marathon in late April 2025. This would be my only significant co-morbidity.

Now, building on the hypothetical new onset of the symptoms you describe, let’s say the CBC shows a leukocyte count of 50×109/L with 45% circulating blasts, platelets of 20×109/L and hemoglobin of 8.0 g/dL. I then contact one of my trusted colleagues in the Mayo Clinic’s Acute Leukemia Group, who is able to see me in the outpatient clinic that same day. The CBC results are very concerning in light of a possible diagnosis of acute leukemia, and I am scared, to be honest. Having cared for acute leukemia patients my entire career, I have often asked myself what I would do if I was diagnosed with acute leukemia. I have always thought that if I remained in reasonably good health, I would likely want aggressive treatment, and would even consider a blood or marrow transplant, if that was warranted and associated with a reasonable chance of success.

To continue this scenario, on further evaluation, flow cytometric assessment of the peripheral blood shows the following immunophenotype of the blasts: CD45 weak, CD19+, CD10+, CD22+, CD24+, CD20-, CD34+, HLA-DR+, CD25+, CRLF2-, CD65/CD15-, CD13+. A bone marrow biopsy shows a hypercellular marrow at 90% cellularity with 75% blasts. Cytogenetic analysis shows the Philadelphia chromosome, t(9;22)(q34;q11) (Ph+) in all metaphases as a sole abnormality. Polymerase chain reaction testing is positive for a BCR:ABL1 gene abnormality expressing the p190 isoform. By fluorescent in situ hybridization (FISH) testing, an IKZF1 deletion is detected as a sole additional abnormality.

Stepping back to reality, the treatment of Ph+ acute lymphocytic leukemia (ALL) has evolved considerably in a favorable direction in recent years. The main advancement has been the addition of tyrosine kinase inhibitors (TKIs)—which were originally developed for the treatment of Ph+ chronic myeloid leukemia (CML)—to the treatment of Ph+ ALL. The leukemia group at MD Anderson Cancer Center has pioneered the addition of TKIs to their hyperCVAD combination chemotherapy regimen, and with the addition of the third generation TKI, ponatinib, has achieved a 6-year event free survival (EFS) rate of 65% and an overall survival (OS) rate of 75%. More recently, a TKI has been combined with an immunotherapeutic agent, the bispecific T-cell engaging (BiTE) blinatumomab, resulting in a 3-year EFS of 91% and OS 77%. Now, a phase 3, multicenter, U.S.-based clinical trial is randomizing patients between the ages of 18 and 70 to hyperCVAD plus ponatinib or another TKI, dasatinib (investigator’s choice), or to a combination of blinatumomab and ponatinib or dasatinib.

For myself, I would opt for enrollment in a clinical trial if one was available. With my age, I would not be eligible for the phase 3 multicenter trial. Outside a clinical trial I would opt for treatment with ponatinib and blinatumomab. Ponatinib is associated with an increased risk of cardiovascular (CV) complications, but is currently used in lower doses with further dose reductions based on treatment response, which has lessened the risk of CV complications. Given my stable cardiac status and symptom-free state, I would favor treatment with ponatinib.

Shortly after my diagnosis I would be hospitalized and started on prednisone at 60 mg/m2, which could continue for as long as 21 days, but as short as 7 days depending on how quickly my white blood cell count and blast count subside. I would simultaneously initiate therapy with ponatinib at 30 mg orally daily, and then add blinatumomab by continuous IV (CIV) infusion after the 7–21-day pre-phase, starting at a flat dose of 9 mcg per day with escalation to 28 mcg per day after 5-7 days if I remain stable. The MD Anderson regimen does not include a steroid pre-phase, but starts therapy immediately with ponatinib and blinatumomab. With this approach, they have seen a low risk—only 12%—of cytokine release syndrome with blinatumomab, with all cases being grade 1-2 in severity, so this would be a reasonable alternate approach. Importantly, I would need to receive frequent doses of intrathecal (IT) chemotherapy to help prevent a central nervous system relapse. Up to 15 doses of IT chemotherapy is recommended, given as 3 doses with each cycle of blinatumomab. Blinatumomab is given for 4 weeks by CIV, with a 2-week break between cycles. Depending on my response to therapy, up to 4-5 cycles of blinatumomab could be given.

I would want my response to therapy to be assessed with sensitive tests for measurable residual disease (MRD) and include testing by next-generation sequencing (NGS) with the clonoSEQ® assay, which assesses for immunoglobulin gene rearrangements up to a level of 10-6. I would also assess the level of the BCR-ABL1 gene by PCR, though studies have shown that as long as the NGS assay by clonoSEQ® is negative (which defines a complete molecular response [CMR]), positivity for the PCR test does not have prognostic significance and may represent mature cells with the BCR-ABL1 gene that are not able to replicate. Once I achieve a CMR, the ponatinib dose could be reduced to 15 mg daily and would then be continued indefinitely to reduce the risk of relapse.

Retrospective studies have shown that if a CMR is achieved within 3 months of diagnosis, there is no added benefit to pursuing an allogeneic hematopoietic cell transplant (alloHCT). In the past alloHCT was indicated for all patients with Ph+ ALL who were felt to be candidates, but now it is being applied less and less, given the efficacy of combining a TKI with blinatumomab or chemotherapy.

My initial disease features at diagnosis suggest that I have a reasonably good prognosis. Hopefully I would reach a CMR within 3 months and not require an alloHCT. Although it is generally recommended that ponatinib continue indefinitely as maintenance therapy, there are anecdotal reports of patients who stopped ponatinib maintenance therapy for varying reasons and did not relapse. So, similar to what has been reported with CML, it may be possible to achieve a treatment-free remission in Ph+ ALL as well.

Obviously, the diagnosis and treatment of Ph+ ALL is a major disrupter of one’s life, and I would seek out the support of family and friends to help guide me through the ups and downs of therapy and monitoring. I would attempt to maintain a regular exercise schedule and emphasize good nutrition throughout my treatment. I have a living will and an advance directive, and I would make sure these are up to date to reflect my current wishes. I would also focus on my spiritual life to help keep a broader perspective on the significance of my illness in the grand scheme of life. As I have observed with so many of my patients, I would attempt to maintain a good attitude and keep a sense of humor in the setting of this life-threatening illness.

Dr. Litzow can be reached at litzow.mark@mayo.edu.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

New Device from Lungpacer Medical Helps Patients with Advanced Cancer

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Doug Evans
President & CEO, Lungpacer

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

People with cancer that affects their lungs may, at some point, need to go on mechanical ventilation to help them breathe. But once they no longer need ventilation, they may struggle to regain the ability to breathe on their own. After watching his son face this challenge, Doug Evans led development of a new treatment that is like a “personal trainer” to help rebuild breathing strength more rapidly. Here, our Curious Dr. George asks Doug, who is president and CEO of Lungpacer Medical, about this approach.

Curious Dr. George: Successful respiration is essential to sustain human life. Patients with potentially lethal pulmonary malignancies may require ventilatory assistance after surgical removal of substantial lung tissue, during pulmonary infections—especially if the patient is immunocompromised, or if the patient suffers from chemo- or radiation-induced lung damage. How might your Lungpacer diaphragm pacing therapy be helpful for patients with advanced cancer who are in need of mechanical ventilation?

Doug Evans: This question is very close to my heart given my personal experience with my son, Cameron, who required mechanical ventilation during his cancer battle.

Every year, 2.5 million Americans need mechanical ventilation—up to 40% die. Diaphragm atrophy is the main reason patients struggle to be weaned off mechanical ventilation and breathe independently. Ventilator-induced diaphragm dysfunction is a big unmet clinical issue.

Cancer patients on mechanical ventilation are dealing with an especially challenging situation. Whether they’ve just undergone surgery, are fighting severe infections with compromised immune systems, or are suffering from chemo- and radiation-induced lung damage, they’re already in a weakened state when they need ventilator support.

The problem these patients face is that, when they go on mechanical ventilation, they’re sedated to keep them calm and prevent them from fighting the machine. But this sedation stops the brain from telling the diaphragm muscle to work. The diaphragm is one of the two muscles in our body that’s constantly working, and when it’s rested for just a few days, it can lose about 50% of its mass. This makes it incredibly difficult for these patients to regain independent breathing again.

Our AeroPace system addresses this by taking control of the signaling from the brain down to the diaphragm muscle. We place a neurostimulation array in blood vessels very close to the nerves that control breathing, using a catheter-based platform that clinicians already know well and use every day. The system exercises the diaphragm muscle while the patient is sedated or sleeping. It’s like going to the gym twice a day to rebuild strength. This significantly reduces the time to wean or regain independent breathing.

Perhaps the most high-profile case of this phrenic nerve stimulation technology is Christopher Reeve, an actor who was paralyzed in a horse-riding accident in 1995. About eight years after the accident, he underwent an experimental surgery to implant electrodes in his diaphragm and help him breathe again without a mechanical ventilator. Now, more than 20 years later, the same phrenic nerve stimulation technology can finally help critically ill patients everywhere—but with no surgery required.

Unlike Reeve’s implant, Lungpacer is a minimally invasive therapy that is easily inserted at bedside and later readily removed when patients are ready to breathe on their own. This is vital because many critically ill patients can’t tolerate or survive a surgical procedure.

For cancer patients specifically, this can be life changing. Our clinical data show we can reduce the time patients spend on ventilators by three days compared to standard care. We can improve muscle strength by about 50%. Most importantly, we can reduce the risk of patients needing to go back on ventilation by 46%—this durability is critical for patients whose immune systems may already be compromised.

I really wish we had this technology available for my son, Cameron, to get him off the ventilator faster. He would have been in much healthier shape. While he ultimately did wean from the ventilator, he tragically passed away several weeks later, and I believe he suffered cumulative effects from prolonged ventilation.

Our mission is to spare other families from that experience. After 70 years without innovation in this space, we’re finally giving vulnerable patients, including those fighting cancer, a real chance at faster recovery and better outcomes when they need it most.

Mr. Evans can be reached at devans@lungpacer.com.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

High-Energy Blue Light Produced by Ultrasound Activates a Promising New Treatment, Sonodynamic Therapy, to Destroy Cancer Cells: An Update

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Stuart L. Marcus, MD, PhD
Founder & Chief Science Officer, SonALAsense

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

A perennial challenge in cancer treatment is figuring out how to kill tumor cells while leaving healthy cells unharmed. Two years ago, our Curious Dr. George asked Stuart L. Marcus, MD, PhD, founder and Chief Science Officer at SonALAsense, how his company’s light-activated drug treatment addresses this challenge. Here, he checks in with Dr. Marcus on the latest developments for this promising approach.

Curious Dr. George: Your flagship treatment employs sonodynamic therapy (SDT), in which focused ultrasound is used to generate a light that activates a metabolite of aminolevulinic acid (ALA) concentrated selectively in cancer cells. This approach results in the oxidative destruction of those cancer cells but not other cells. How does that work? And what can you tell us about how effective it is for cancer patients?

Stuart L. Marcus, MD, PhD: To answer how SDT works, we have to first understand that SDT is a new, noninvasive form of a light-activated drug therapy called ALA photodynamic therapy (PDT). ALA PDT targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer protoporphyrin IX (PpIX) accumulates primarily in cancer tissue to such a specific extent that the U.S. Food and Drug Administration (FDA) has approved ALA-induced fluorescence in a number of different cancer settings. For instance, urologists use it to help identify bladder cancers through blue light cystoscopy. Neurosurgeons also use it every day as a visual aid to resect high-grade brain cancers, such as glioblastoma multiforme (GBM), employing blue light resection and fluorescence-detecting surgical microscopes.

When PpIX is exposed to the high energies of blue light, energy is transferred from PpIX to molecular oxygen (the photodynamic process), making it highly reactive. In 1999, the FDA approved a topical ALA PDT blue light system, which I and my team at DUSA Pharmaceuticals created for treatment of the precancerous skin condition actinic keratosis. That system, now marketed by Sun Pharmaceutical Industries, has treated over 4 million people to date. ALA PDT has also been successfully used in investigational clinical studies to treat recurrent GBM (rGBM) using the ingested dye Gleolan as the source of ALA and by inserting fiber optics within the tumor which deliver laser light. Although I considered further developing PDT for rGBM, this system is so invasive and complex that, in my opinion, commercialization is moot as the treatment is very difficult to standardize.

Instead, with ALA SDT, we use MR-guided focused ultrasound to safely create light in tissue through a process called sonoluminescence. In preclinical studies, we and others have shown that this approach can effectively and selectively kill gliomas in animal models through the PDT process and can result in complete clearing of the cancers, with 100% of the animals surviving. In a first-in-man energy dose-ranging study at the Ivy Brain Tumor Center, each of 10 rGBM patients received our intravenous form of ALA, which is called SONALA-001, and we applied SDT to one-half their tumor. The patients’ tumors were surgically removed in 4 days, and oxidative changes (lipoperoxide liberation) and apoptosis were compared in the treated and untreated halves of each tumor. We found that ALA SDT selectively caused PDT oxidative damage to the treated tumor half.

We have now treated 8 rGBM patients in a therapeutic phase 2 dose-ranging clinical trial. We have also treated 15 children with the deadly brainstem cancer diffuse intrinsic pontine glioma (DIPG) in another phase 2 dose-ranging study, in which we treat the entire brain stem. We have seen no dose-limiting toxicities in either trial, even in patients treated monthly for 10 consecutive months, attesting to the tumor-specificity of ALA as well as the lack of cumulative toxicities.

The heme pathway is a universal pathway, and the tumor-specific PpIX accumulation response to being provided with excess ALA gives us hope that SDT will prove therapeutic for many types of tumors. In December 2024, the Advanced Research Projects Agency for Health (ARPA-H), awarded our company a grant of up to $46 million USD to extend our development of SDT to the treatment of blood cancers, resulting in devices which would use SDT to treat blood cancer cells in the blood as well as within the body.

Dr. Marcus can be reached at smarcus@sonalasense.com.

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How Would a Mayo Clinic Oncologist Manage His Own Chronic Lymphocytic Leukemia?

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Sameer A. Parikh, MBBS
Associate Professor of Medicine & Assistant Professor of Oncology, Mayo Clinic (Rochester, MN)

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Cancer patients often ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Mayo Clinic oncologist Sameer A. Parikh, MBBS, how he would handle his own diagnosis of chronic lymphocytic leukemia (CLL). Dr. Parikh is an Associate Professor of Medicine and Assistant Professor of Oncology at the Mayo Clinic in Rochester, Minnesota.

Curious Dr. George: Please imagine this hypothetical scenario: You are an active clinical and research oncologist in general good health. However, lately, you have felt less energy than usual, have been feeling fatigued at night, and have lost some weight without dieting. You decide to visit your primary care physician for a check-up. On physical examination, she notes that you are a little pale, and you have moderately enlarged lymph nodes in the axilla and groin, as well as a slightly enlarged liver and spleen. She orders several lab tests., which show that your hematocrit is 38, hemoglobin 12, WBCs 90 000 with mostly mature lymphocytes, and you have a proper number of granulocytes and normal platelets. You receive a provisional diagnosis of chronic lymphocytic leukemia. How would you proceed?

Sameer A. Parikh, MBBS: I chose to study leukemia because my maternal aunt passed away from acute myeloid leukemia at the age of 44, just three months after her diagnosis. Although chronic lymphocytic leukemia (CLL) is different, the word “leukemia” evokes feelings of helplessness and anxiety, making it difficult for anyone to process information properly. In your hypothetical scenario, although it would not be easy, I would make sure to collect my thoughts and give the diagnosis some time to process. I would also discuss the diagnosis with my close friends and family to garner all the support I would need as I navigate this period of uncertainty, with regard to outcomes following the diagnosis. I would then research the top experts in CLL and ensure I secure an appointment with a specialist. It’s crucial to consult with someone who specializes in CLL to obtain the most up-to-date information, as studies show that expertise-specific care leads to better outcomes.

Confirming a diagnosis of CLL is extremely important, and it is typically done via a peripheral blood flow cytometry study. Unlike other malignancies, patients with early-stage, asymptomatic CLL are not treated at the time of initial diagnosis, unless a few specific, well-established criteria are met (as outlined in the 2018 guidelines of the International Workshop on Chronic Lymphocytic Leukemia, iwCLL2018). This is due to decades of research demonstrating that early intervention in CLL does not lead to improved quantity or quality of life. It is essential to understand this because it challenges the common belief of “find cancers early, so you can fix them early.”

In this imaginary case, although my WBC count is high, it appears that I would not need CLL-directed treatment at this time. One of the first questions I would have for my CLL specialist is how quickly my cancer is likely to progress to the point where treatment would be necessary. To better understand the biology of the underlying CLL, we would typically obtain several genetic tests, including IGHV mutation status, serum beta-2 microglobulin, TP53 mutation status, and the CLL FISH profile. The collection of these tests would allow us to calculate the CLL international prognostic index (CLL-IPI). Based on the total score, my CLL could be classified into low risk, intermediate risk, high risk, or very high risk of disease progression requiring treatment, with a 5-year need for therapy at 20%, 50%, 70%, and 90%, respectively for the corresponding CLL-IPI risk scores.

During this active surveillance, or the so called “watch and wait” phase of the disease process, it would be important to acknowledge the anxiety or emotional distress associated with untreated malignancy (“watch and worry”). Having the support of loved ones through this journey and acknowledging that treatment may be needed in the not-too-distant future would be exceedingly important, particularly given that there may be no external signs of cancer. In addition, it would also be important to see my primary care physician on a regular basis and stay up-to-date with cancer screening measures, including undergoing a colonoscopy and prostate cancer screening as recommended. Also, I would also schedule a yearly dermatology visit for a full-body skin check, given the increased risk of skin cancers in patients with CLL. Finally, I would follow the CDC recommendations for immunization in an immunocompromised host, and stay up to date with all the vaccinations.

Once treatment is needed, I would ensure to repeat the genomic tests to confirm that nothing has changed. Currently, there is no scenario in the management of CLL where chemotherapy is indicated. Instead, treatment consists of a fixed duration (12 to 24 months) of combination therapy with pills (either Bruton tyrosine kinase inhibitors or BCL2 inhibitors) and immunotherapy infusions (such as monoclonal antibody infusions like obinutuzumab). If these treatments stop working, newer options are available, including BTK degraders, bispecific antibodies, and chimeric antigen receptor (CAR-T) therapy, in addition to an allogeneic stem cell transplant.

While we would aim to cure my CLL with the treatments available, it would be important to remember that CLL remains an incurable disease and is managed as a chronic condition. I always remind my patients that this journey is a marathon, not a sprint, and we will grow old together. My goal as an oncologist, which would also hold true in my own case, is to ensure my patients reach their average life expectancy (and hopefully beyond that) without considering CLL with a high quality of life. With the tools we have at our disposal today, I am confident that we can achieve this objective for the majority of our patients.

Dr. Parikh can be reached at Parikh.Sameer@mayo.edu

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