At 10:21 a.m. Los Angeles time on Monday, August 21st, the moon covered 62% of the sun. In Oregon and across the US, there were 2.3 minutes of total darkness. Scientists had been informing everyone about this upcoming event for many years, and it occurred exactly on schedule: a natural event.
This awesome illustration of nature at work had a powerful impact on many people. They witnessed firsthand that science is an extraordinary tool to understand the world around us, from the planets and stars above, to the molecules within every cell of our bodies. It is urgent that we recover the trust in our scientists and the understanding that they seek the truth—truth can help all of us.
And on Monday, we saw hard evidence that truth has consequences: there was an eclipse at 10:21 a.m.
Using the scientific method
Across the board, the scientific method produces real, verifiable results. Just like the method you used to solve math problems as a child: if a train traveling at 40 miles per hour departs at 9:00 a.m. for Zurich, which is 80 miles away, what time will it arrive? Answer: 11 a.m. Math, plus our observations of train travel, give us that answer. Now, a flight from JFK to Zurich has a less dependable arrival time because we’ve observed many variables that alter the outcome. Scientists worry about variables and warn about circumstances when results can be different.
Right now, in August 2017, there are many scientific results we need to understand and trust, as well as some for which uncertainties and variables must be considered. The existence of variables and unknowns doesn’t detract from the dependability of those things we know to be facts.
Bananas instead of grapes?
But before I turn to how trains running on time and real facts impact decision-making for myeloma patients, a brief comment on the public controversy about climate change. In this case, there are many observations from all around the world that contribute to our factual knowledge. Researchers from Woods Hole Research Center have documented that Alaska’s vast permafrost is melting and will have retreated dramatically by 2050. Global warming has had a striking impact on the wine-making regions in Italy. The hot, dry conditions (named “Lucifer” this year) mean harvest is much earlier and berries have too much alcohol and fat. That’s a fact so significant it led one wine grower to comment, “We’ll need to plant bananas and pineapples.” And of course, we have all experienced strange weather with drought, flash floods, and crazy storms.
In other words, facts—in those cases about global warming—have an impact.
Variables in new myeloma treatment
Facts have an impact in myeloma research, too. If we look with sensitive imaging at undiagnosed myeloma, we know that 20% of the time, we will find evidence of early bone disease. Starting first or "frontline" therapy with triple therapy (such as VRd) in 2017, we know that only 2% to 3% of patients will not respond. These are basic facts we use to guide decision-making.
However, for newer facts, we must be more cautious. Some variables mean the trains may not run on time.
For example, with the new CAR T-cell therapy, we don’t even know the train schedule, let alone if the trains will run on time. Dramatic benefit has been reported with the anti-BCMA CAR T-cells in patients with advanced myeloma. However, not all patients have responded, and some have had severe, even life-threatening side effects.
To justify this treatment’s high cost and toxicity, not only must patients with advanced disease benefit, but there must be a sustained value: a significant depth and length of remission, which may benefit patients with earlier disease. Can CAR T-cell therapy achieve MRD negative status in some patients? The answer appears to be yes.
However, the CAR T-cells become “activated” in response to the BCMA antigen on the surface of myeloma cells. If there are very few myeloma cells left (low-level MRD), there may not be enough CAR T-cell activation to eradicate remaining cells. Initial “de-bulking” or reduction of myeloma cells through aggressive treatment can be very effective. Perhaps monoclonal antibodies against BCMA (directly or bispecific linking in with other cells such as T-cells) or some of the other new monoclonal antibodies will prove to be more effective than CAR T-cells in eradicating myeloma cells completely.
Before going overboard with one approach to curing myeloma, we need to step back, look at the facts, and reevaluate our overall goals, expectations, and potential costs. If CAR T-cell therapy can cure myeloma, maybe a $500,000+ cost per patient can become justifiable. If it cannot, then maybe not.
Science may be able to accurately predict total solar eclipses, but for now, our job is to unearth as much evidence as possible to put an end to myeloma. Myeloma research has progressed with lightning speed over the last decade. With new facts emerging every day, it seems as though we are indeed moving forward at the speed of light. Einstein would be pleased.
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