Revolutionary new cancer therapies come with big risks. Drug makers must be prepared

Personalized cell therapy may have come of age with the recent approvals of two novel drugs, Kymriah and Yescarta, that genetically manipulate patient’s own immune cells to fight their cancers. Yet pharmaceutical companies face many challenges, including several key ethical and social issues, if they are to make these new therapies a success.

These new drugs, the first in the new family of CAR-T cell therapies, could revolutionize the treatment of blood cancers and make inroads into the treatment of solid tumors. They work by isolating immune cells known as T cells from a patient’s blood, genetically engineering these cells to produce receptors that recognize specific tumor cells, growing many millions of copies of these cells in a lab, then infusing them back into the patient. If all goes well, the engineered cells recognize and kill the patient’s tumor cells.

Early results have been impressive, with cancer essentially eliminated — at least in the short-term — in many patients who had failed standard therapies and had no other options.

Despite some exciting clinical successes, the companies selling these drugs face a variety of challenges. On the business side, they must figure out how to manufacture the drugs affordably and reliably, secure and maintain sufficient reimbursement to justify the research and development and manufacturing investments, and convince physicians to embrace this new and powerful, yet complicated, treatment paradigm.

CAR-T pioneers must also navigate the hype and hope surrounding the field. While the approval of Novartis’s Kymriah was narrowly tailored to resistant or relapsed forms of leukemia and Gilead’s Yescarta was limited to lymphoma patients who had failed previous treatments, the pressure to expand access to these drugs will be immense.

The valuations that Wall Street has placed on firms commercializing CAR-T therapies suggest an expectation that these therapies will rapidly move from treatments of last resort to the therapeutic front lines. While such a transition is necessary if CAR-T therapy is to fulfill its promise, this change should be carefully and deliberately managed to avoid missteps that could tarnish the field and limit its potential.

The immediate priority must be getting these treatments right for patients with no other options. CAR-T therapies will almost inevitably kill some patients faster than their underlying cancers would have. So companies and clinicians must redouble their efforts to minimize the serious and sometimes fatal side effects that accompany these therapies and developing strategies to manage them when they do occur.

Companies commercializing these therapies must be open about the possibility of treatment-related deaths and severe side effects to patients, physicians, regulators, and investors. They must also be prepared to rapidly, transparently, and convincingly address these events when they occur. These efforts should include everything from managing expectations upfront by developing educational materials for patients and coordinating with patient advocacy groups to developing in advance contingency plans and crisis communication strategies.

While any death resulting from medical treatment is tragic, to some patients the potential benefit of CAR-T therapy will merit that risk. This calculation will change rapidly, however, as CAR-T therapies move toward patients with earlier-stage cancers who have a wider array of options. This is likely the case for many individuals. It may also be the case for society more broadly where adverse events could hinder the development of CAR-T therapies and limit their potential. Indeed, one only need to look at the historical development of gene therapies to see how high-profile adverse events among research participants — especially those with other therapeutic options — set back clinical research by years and jeopardized investor and regulator confidence in the field.

Despite the clamor of individual patients and patient organizations to rapidly expand the use of CAR-T therapy, and the outsized financial expectations and accompanying pressures, companies need to resist the temptation to expand CAR-T therapy too far and too fast. They should instead take the time to refine these promising therapies in smaller last-resort patient populations — perhaps with nudging from relevant government agencies.

Although it may seem counterintuitive, going slowly with this exciting but complicated new type of cancer therapy offers the best chance to turn personalized cell therapies into a medical and financial success.

Aaron D. Levine, Ph.D., is an associate professor in the Georgia Tech School of Public Policy whose work has focused on the role of policy and ethics in the translation of emerging biomedical technologies. He also conducts ethics and policy research for the National Science Foundation-funded Engineering Research Center for Cell Manufacturing Technologies, which supports engineering research related to the manufacturing of CAR-T and other forms of cell therapy.