Musing on Medical Marvels

Carlson and Nelson Endowed Director, Center for Individualized Medicine, and Vasek and Anna Maria Polak Professor of Cancer Research, Mayo Clinic in Scottsdale, Arizona

It was circa 1999. I can picture the patient vividly: A mustachioed, unfailingly polite – but exhausted – middle-aged man holding a white tissue to his bleeding nose. A Ugandan immigrant, he was dependent on platelet and red blood cell transfusions, and his myeloma progressed following conventional chemotherapy and autologous hematopoietic cell transplantation, as well as a boatload of alkylating agents and dexamethasone. His disease had left him largely bedbound.

Hallway conversations among the myeloma cognoscenti were alive that year with news that the great innovator Bart Barlogie, MD, had evidence of responses in patients with late-stage myeloma to, of all things, the notorious drug thalidomide. Younger in those days and more risk-tolerant, we found a wholesaler in the United Kingdom, sought permission from the regulators for emergency use, and gave thalidomide a try.

After receiving treatment, the patient picked himself up out of bed and walked. Some years later, he brought me a small stone carving from his native country depicting a person helping another off the ground – I keep it in my home office even today.

At the 2017 ASCO Annual Meeting, more medical miracles were on display as the tsunami of immuno-oncology and precision therapeutics engulfed the proceedings. There was news about designer drugs, activated T cells savaging solid tumors, and patients with refractory lymphoma and myeloma achieving complete remissions by treading the same cellular therapy paths carved by patients with childhood leukemia and chronic lymphocytic leukemia (CLL).

I sat at the back of the hall as Siddhartha Mukherjee, MD, DPhil, delivered his excellent guest lecture about the “deep personalization” of medicine during the meeting’s opening session, contemplating chimeric antigen receptor T cells and other medical marvels I have been honored to witness as a myeloma doctor, from thalidomide to lenalidomide, bortezomib to carfilzomib, and daratumumab to venetoclax. Outside my own expertise, I have seen ibrutinib change the treatment of CLL, as well as the about-face of chronic myeloid leukemia and hairy cell leukemia as a result of new therapies.

Listening to the address, I thought about a family friend and frequent tobacco user who developed an advanced squamous cell carcinoma of the lung and how genomics and checkpoint inhibitors have made heavy inroads in a disease I had always associated with a fairly rapid demise. I applauded heartily at the proven logic that a mutation affecting a novel TRK fusion protein responds to a matched small-molecule inhibitor 75 percent of the time. Most of all, I thought about this great energy vortex of scientists and clinicians, charitable foundations, government agencies, entrepreneurs, angel investors, venture capitalists, biotech and Big Pharma, diagnostic companies, contract research organizations, patients participating in trials, and – yes – the regulators who have worked together in networks of mutual urgency and shared visions to accelerate transformative advances in just 20 years that allowed a hematologist to witness multiple patients respond to a repurposed drug.

Reality bit deeply into my red apple of optimism later that day. It began insidiously with a tale, possibly apocryphal, from an employee of a medium-sized pharmaceutical company about a niece who earned an A+ in her middle school biology class on an essay about why drug companies were bad.

Later, I logged into Twitter to see what colleagues were saying about this great generation of oncology; one well-meaning group was having a tweetathon saying “they” (drug companies) were conspiring to bankrupt and hoodwink patients. CAPS LOCK was employed to express with vehemence how terrible it was that a drug that extended remission by an astonishing 10 months cost more than the current standard. Compounding my dismay was the tone of colleagues on the same subject during a question-and-answer period at another session during ASCO’s annual meeting.

It all reminded me of Henry Kissinger’s adage: “Academic politics are so vicious precisely because the stakes are so small.” But in hematology/oncology, they aren’t. The stakes are high and every member of the team, including our colleagues in industry, deserves recognition for the good that has been wrought.

It would be a hardened disciple of commercial purity who failed to acknowledge publicly that advancing inventions, supporting serendipitous drug-repurposing discoveries, conducting clinical trials that cost millions of dollars to run, and manufacturing and distributing life-saving therapies are almost certain not to happen without the incentive of return on investment. I am not defending high drug prices or markups. I understand the vexation of colleagues, I sense the urgency patients feel, I worry about the political winds of research funding, and I don’t like hyped claims, “manageable toxicity,” or dodgy statistics any more than the next person. But I do wish for fair and balanced coverage.

It seems to me that every member of the medical-marvels team deserves respect even while the uncertainty and missteps of transformational change are still fogging the conversation.

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