1838_ASCO_Cell__Gene_blog_img-786863-editedKatie Blodgett and Robert Rovner co-authored this post with Sharon Karlsberg. 

Adoptive cell immunotherapy got top billing at this year’s American Society of Clinical Oncology (ASCO) meeting with its designation as the 2018 clinical cancer “Advance of the Year,” and for good reason. The first generation of chimeric antigen receptor T-cell (CAR-T) therapies, set in motion with the late 2017 approvals of Kymriah (Novartis) and Yescarta (Kite, a Gilead company), are among the most anticipated cancer breakthroughs to date.

Amid the excitement, significant opportunities remain to improve access and outcomes for patients who could benefit from CAR-T. I sat down with Dr. Michael R. Bishop, director of the cellular therapy and stem cell transplant program at the University of Chicago, at ASCO to learn more about this exciting and evolving space. Together, we uncovered several avenues for manufacturers and healthcare providers to better meet the needs of patients eligible for CAR-T therapies.

 

Educational Opportunities to Improve Today’s Reality

While the pipeline holds the promise of next-generation CAR-Ts, more needs to be done to ensure that the first crop of CAR-T therapies is available to those in need—and those who qualify—today. These highly personalized, custom-made treatments present logistical, clinical and financial challenges for institutions, oncologists, patients and their caregivers. Here are four educational needs that could be addressed by pharma manufacturers or other healthcare stakeholders to improve today’s reality:

  1. Education for healthcare institutions: Access to CAR-T therapies is currently limited to a small subset of the nation’s hospitals, mainly the original clinical trial sites. To make these therapies more broadly available to patients, manufacturers and existing treatment centers can help potential new sites build the necessary infrastructure and services. At the University of Chicago, Dr. Bishop and his team began thinking about offering CAR-Ts years before the therapies were commercially available. The team subsequently spent 12 months developing more than 60 internal protocols to streamline the process of administering CAR-T therapies to patients outside of clinical trials. Sharing such detailed expertise can help hospitals and other institutions evaluate their current capabilities and determine which areas to strengthen or supplement.
  1. Education for community oncologists: While there’s been a lot of buzz about CAR-T therapies in the scientific literature, there’s a continuing need to educate oncologists broadly to drive referrals to existing treatment centers. This will help ensure that all eligible patients have access to high-quality, safely managed CAR-Ts. By growing their understanding of what CAR-T therapies are and what’s involved both for clinicians and patients, community oncologists will be better equipped to identify eligible patients, and to dispel myths that certain characteristics might automatically make a patient a poor candidate for CAR-T.
  1. Education for patients and caregivers: Like all new oncology therapies hailed as medical breakthroughs, CAR-Ts have generated tremendous excitement among cancer patients and their caregivers. Optimism surrounding the potential of these treatments can quickly turn to disappointment, however, when patients learn that these therapies might not yet be available to them. To address the disconnect in his practice, Dr. Bishop tells patients, “Hopefully we will have a CAR-T cell therapy for your cancer in the near future, but this isn’t [available] right now.” Even after patients understand who is and isn’t eligible, manufacturers and providers need to educate patients on CAR-T basics including how the therapy works, what to expect during treatment and how to identify toxicities (like cytokine release syndrome) before they pose greater risks.
  1. Education for payers: An audience member at ASCO asked Dr. Carl June, director of the Center for Cellular Immunotherapy at Penn Medicine’s Abramson Cancer Center, about the costs associated with CAR-T therapies. Not hesitating, Dr. June reminded the audience that it wasn’t long ago when emerging cancer therapies called monoclonal antibodies were thought to be too expensive for widespread use. Over time, manufacturers found ways to bring down production costs and make those drugs more widely accessible. In the case of CAR-Ts, the price point needs to align with the products’ therapeutic value while balancing the burden on the overall healthcare system. To get there, manufacturers should share evidence with payers on the long-term value that these therapies provide. Leading pharma companies are also exploring opportunities to partner with healthcare authorities to co-create solutions that mitigate the risks associated with high up-front costs.

Looking to Tomorrow’s Innovations

Through education, manufacturers and healthcare providers can allay some of the current concerns associated with first-generation CAR-T platforms. Even so, challenges such as inconsistent response rates, significant toxicities and slow production timelines may limit the utility of currently approved CAR-Ts. By developing next-generation cell therapy platforms, manufacturers such as Cellectis, Ziopharm Oncology, Adaptimmune Therapeutics and Allogene Therapeutics are confronting obstacles like lengthy turnaround times, scalability and expansion beyond hematological malignancies. Dr. Bishop, Dr. June and many others believe that these newer versions of CAR-T therapies hold the key to expanding this paradigm-shifting treatment modality to much broader patient populations.

One example of what’s to come includes “off the shelf” alternatives to CAR-T therapies, which are being developed to provide a readily available supply of products and CAR-Ts that use non-viral, plasmid-based delivery systems of genetic material into T-cells. They’re expected to shorten CAR-T production time from about three weeks to less than two days. As Dr. June shared during a Q&A session at ASCO, if these products are proven to have “significant efficacy and safety,” then “they would clearly change this entire model.”

 

Additionally, scientists are developing TCR-modified T-cells—T-cells redirected for universal cytokine killing—and armored CARs to provide a greater array of potential therapeutic targets. By increasing the ability to thrive in the tumor microenvironment, we might get closer to expanding cell therapy into solid tumors. 

The CAR-T therapies available to patients and clinicians today are merely a preview of the advancements yet to come. As cellular science becomes more targeted and routinely employed, patients will benefit from more options, faster treatment protocols, and better safety and efficacy profiles. Dr. Bishop and I agree that if we were to fast-forward to ASCO 2028, personalized medicine and solid tumor CAR-T therapies are sure to be cancer innovation headliners.


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Topics: Sharon Karlsberg, ASCO, hospitals, CAR-T, therapeutic oncology, immunotherapy, pharma manufacturer, ASCO 2018, cancer care, Robert Rovner, Katie Blodgett