Hope on the Horizon: Research Webinar Recap


On January 30th, we hosted a webinar about the latest ground-breaking developments in childhood cancer research, with a specific focus on immunotherapy and precision medicine.

It’s really important to have realistic expectations [around precision medicine] and much more study is needed.
— Dr. Dan Wechsler

The full recording of that webinar is available at the end of this post but we wanted to share some highlights, since it was jam-packed with valuable information:

Dan Wechsler, MD, PhD, of Children’s Healthcare of Atlanta - and a Children’s Cause Board Member - kicked off this hour-long event with a presentation on the “Promise and Pitfalls of Precision Pediatric Oncology.”

Dr. Wechsler started off by describing the vision of precision medicine in a way that’s easy to grasp:

“What we would like, ideally, to do with cancers in both children and adults is do what we do when someone has a bacterial infection,” said Dr. Wechsler.

He explains: when someone has a bacterial infection, we take a sample of the bacteria and find out if it is sensitive or resistant to antibiotics. The treating physician then knows exactly which medication(s) will treat that exact infection. It’s more complicated with tumors, so oncologists traditionally practiced “one size fits all” medicine in cancer therapy. But now, with precision medicine, we’ve started to move toward tailoring treatment to the individual patient.

Dr. Wechsler also walked us through the ‘life cycle’ of precision oncology, as seen in this slide:

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Dr. Wechlser discussed different types of sequencing that are available, emphasizing that not all sequencing is the same. The average cost of sequencing is currently about $5,000 per specimen, with a turnaround time of about 2-4 weeks.

He shared some of the many reasons why success in precision medicine is still hampered by a lot of roadblocks in pediatrics:

  • There are over 20,000 genes in the human genome and we don’t know much about many of them. Just because we find a mutation doesn’t mean we fully understand it.

  • Even if genes are well understood, there may be no specific drugs available, like in patients who have a mutated gene that predisposes them to tumor development (p53 in Li Fraumeni).

  • Even if there are drugs available, they may not be approved yet for use in children.

  • We still don’t know enough about which combinations of drugs - either with standard therapies or other gene therapies - will be most effective.

  • Cost, turnaround time, a lack of clinical trials and limited drug availability are additional challenges in precision medicine.

But despite those challenges, Dr. Wechsler emphasizes that genetic sequencing is still incredibly valuable, even when it doesn’t unveil an option for immunotherapy. For instance, we learn information about cancer biology that furthers the field of study and often the sequencing can help confirm or refine a diagnosis and give additional information about how a specific patient might respond to a particular treatment.

Sequencing also can reveal information that points to a predisposition to cancer, which can have implications for the patient - like avoiding radiation therapy - and, of course, implications for other family members. Currently 10-15% of pediatric cancers are thought to have a genetic predisposition but that number could be as high as 30-40%. “All of these issues highlight the need for genetic counselors to be involved in precision medicine,” says Dr. Wechsler.

Next, we heard from Dr. Robbie Majzner, a pediatric oncologist at Stanford. Dr. Majzner gave an overview of different types of immunotherapy:

  • Monoclonal Antibodies: A ‘tag’ that recognizes something specific on the cancer cell and marks that tumor cell for targeting by the immune system. This has been successful with B-cell lymphoma, revolutionizing adult and pediatric lymphoma treatment.

  • Antibody-Drug Conjugates: Hook chemotherapy, toxic or radiation directly to an antibody to target specifically to a cancer cell, which is less toxic than systemic chemo but still more aggressive than an antibody by itself. An example is brentuximab, a conjugate used for treatment of Hodgkin lymphoma.

  • T-cell Checkpoint Inhibitors: T-cells are the most potent immune cells and can recognize and kill mutated cancer cells. The discovery of checkpoint inhibitors - which protect healthy cells from T-cell attack - won the Nobel Prize last year but the advances from that breakthrough have mostly benefited adults. That’s because most pediatric tumors lack mutations so there isn’t anything for the T-cells to search for and react against.

  • CAR-T cells: Chimeric Antigen Receptor (CAR) combines an antibody with the T-cell receptor through genetic engineering. The result is a man-made synthetic receptor that seeks-and-destroys cancer cells. “This has really revolutionized the care of children with relapsed ALL,“ said Dr. Majzner. “It’s really been an amazing thing to watch, a technology that was developed by academics in the laboratory go through iterations with improvements in technology to become a very clinically relevant therapeutic and also first-in-class to be FDA approved for the treatment of children with cancer.”

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The dream would be that we ultimately get to a place where we need limited chemotherapy, if any, and we can just use immunotherapy and do it at a point where there’s less disease burden so that the toxicity is not as much of a concern.
— Dr. Jennifer Willert

Our final presenter was Dr. Jennifer Willert, a hematologist-oncologist currently working for Novartis Pharmaceuticals. Dr. Willert discussed the manufacturing process of Kymriah, the first FDA-approved individualized immunotherapy (CAR-T) for pediatric and adult lymphoma. Kymriah - approved in 2017 - is the commercial version of the therapy famously used to treat Emily Whitehead, the first pediatric patient to receive CAR-T treatment, back in 2012.

The commercial version of Kymriah is approved for patients 18-and-over but there are exceptions for younger patients, plus a number of clinical trials in the pipeline. Today, says Dr. Willert, Novartis is focused on improving access to this therapy in the US and globally and ensuring that it is delivered safely at all available centers.

“Most of us in the field are really dreaming of a future where we can utilize the immune system rather than toxic agents like radiation and chemotherapy and bone marrow transplant … in order to really cure patients,” says Dr. Willert.

“These are little kids and young adults that have their whole life ahead of them and late effects are significant. We are hoping we can minimize this with this therapy. Patients that have received CAR-T are able to go home and go to school and play and be with their families within a month of treatment and have a pretty normal immune system within one month to two months and that just isn’t the case in the transplant world.”

The full webinar recording is available here:

Our next webinar will take place on March 27 and will revisit the Externally-Led Patient Focused Drug Development conference on chemotherapy-induced hearing loss that we held last fall. If you’d like to receive the finished report from that workshop and information on webinar registration, let us know here:

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Jessica Kean