Not the Real Thing
If we wait for the moment when everything, absolutely everything, is ready, we shall never begin.
Ivan Turgenev, Virgin Soil
Shortly before Daniel Bergsagel discovered melphalan as the first effective myeloma drug in 1962, MD Anderson Cancer Center didn’t even accept myeloma patients, reasoning there was little-to-nothing that could be done for them.
What few treatments existed might have helped a handful of patients for a little while. Radiation for solitary tumors was an option. Some treating physicians used the first “standard treatment” of sorts in myeloma. When Robert Kyle gave his myeloma history talk to patients, one of the gems people would remember long after was his example of how it was debunked.
Rationale for the “treatment” was based on a 1948 study by a physician in Stockholm, Sweden, who was the first to get access to a new drug from Germany called urethane (not the kind in sneakers). It seemed to inhibit growth of myeloma in lab mice. Since he had nothing much to offer, two of his patients consented to try it. In his published paper, he reported one of the two had some noticeable impact on myeloma cells, the other had none.
Statistically speaking, that’s a success rate of fifty percent. And mostly based on that study, urethane became a standard therapy in myeloma in much of the world for the next fifteen years…based on the partial success of one patient! That would be absolutely unthinkable now, considering clinical trial standards. But in the late 1940s through the early 1960s, what else was there for myeloma patients other than – as MD Anderson and many clinics around the world did – being sent home?
The few myeloma specialists, treating more than ten a year probably counted, around then were ambivalent. Kyle even used it more than a few times, sometimes with favorable results, but not over time.
Other patients saw community oncologists who rarely, if ever, treated myeloma and often resorted to old textbooks and journal articles for guidance. “Urethane is good enough for experts,” they might reason, “it should be good enough for me, and it might be the only choice.” But no one was impressed, the best they could hope for was to delay the inevitable.
Cooperative clinical trials could provide answers. The first clinical trial in myeloma, conducted in 1963, compared the standard treatment urethane to a placebo: cola syrup. Its conclusions were staggering and simply understood.
Simple because one didn’t have to have more than a cursory knowledge of graphs to understand their significance after a second or two. Staggering because the curves almost overlapped. But looking to the right side of the readout, with the small number who survived after eighteen months showed a screaming distinction: the cola syrup placebo had a slightly better survival rate than urethane.
When Kyle showed the slide of a bottle of urethane next to a can of Coca-Cola, the graph on the next slide always caused an ironic laugh from the audience. The distance of time and experience made it funny. When the study results became known for the first time, it was inconceivable anyone at all would have seen humor in the demise of urethane as a myeloma treatment.
This post marks the end of the first four months of this Substack as well as the first Wednesday post in August to recap some past articles. Those of you who have been reading since the beginning have noticed a few patterns. Those who haven’t might be interested in some they missed. Click the links below if you are.
All posts overlap in some way to affect the living history of myeloma, not just events beginning in the 19thcentury. I’ve also written about some of the key individuals – many more are still to be featured. Occasionally I’ll feature book reviews about issues affecting the community. I’ll do the same with sporadic updates on public policy issues with connections to myeloma.
My goal is not just to try to explain myeloma’s past, but to use it to inform the present and think briefly about the future. I hope readers, like me, will look at things they’ve taken for granted for years and decades. And while doing so, never lose sight of the past, of the ideas produced, and the how they impact patients and the community.
Here is a recap of some of the history articles. It took decades to define the symptoms of the first patient who died of what was later determined to be myeloma. And we learned from when myeloma was defined that nothing much happened in terms of patient outcomes for 120 years, as the anecdote above sadly confirms.
Yet at the same time one treatment was deemed to be a dud, a young doctor at MD Anderson in Houston discovered myeloma’s first effective treatment, melphalan, which was arguably the seminal discovery to treat the disease. Nor was it understood how cancer centers were an essential part of President Kennedy’s New Frontier vision in the 1960s.
And we took a short detour to learn about how bone strengthening drugs, bisphosphonates, were pioneered in myeloma after a serendipitous event in Switzerland. Now the class of drugs is not just used in myeloma, but is arguably the most prevalent type used in all cancer treatment as well as other diseases like osteoporosis.
Those weren’t the only historical events. Next week I’ll feature some articles about important personalities, which add insight and further discoveries to those cited above.
This Sunday, we’ll get some life lessons from another myeloma pioneer.
Photo and slide courtesy of Dr. Robert Kyle.