Many of us, most likely, read as much as we can about CAR-T treatments. Not that there is an abundance of data out yet for the multiple myeloma CAR-T products that are at late development stage. Much of what we find are patient/caregiver testimonials, some with positive results, some not so. Once in a while we may stumble on a blog or chat room post where one of our fellow blood cancer patients will be, or has been dosed with a second dose of CAR-T cells after failure to suppress the blood cancer with the first dose.
And this raises the question : ‘What are the outcomes with a second dose of CAR-T ?’
Before we continue you need to know that there are NO data available (yet) from myeloma CAR-T trials that will give us an answer. The only guidance we have is from a presentation at last month’s ASH conference. The CAR-T products used in this study involved treatment of other hematological cancers, mostly some of the lymphoma’s and leukemia’s, where few patients were given a second dose. The patient pool was small (44 patients) and the study completed at the Fred Hutchinson Cancer in Seattle, WA was a retrospective study. In other words, researchers looked at past patient outcomes and try to draw inferences or correlations using statistical analysis.
The original patient population from which this patient pool was culled was heavily pretreated, as is the case with the majority of CAR-T trials. When patients learn the news of their CAR-T failure or relapse of disease they will most likely have none to very few other options left, The medical/scientific community is only a the beginning of an understanding of why some patients have a favorable response to treatment and others don’t. VERY few patients have a more positive outcome from a second CAR-T infusion than from a first one. Some patients, though, may still wish to proceed with a second infusion, even with low odds of a positive outcome and despite the associated costs and risks.
One of the researchers indicated, ‘Although the results of the second infusion are not as good as the first infusion, some response can be achieved in a population without other therapy options.’
The data presented ASH show that ‘ … the second dose of cells didn’t have a dramatic effect for most of these patients in this dire situation. In fact, the cancers were still growing in half of them a month later. But there were glimmers of success. One month after the second infusion, the cancers of eight [out of 44] patients had disappeared; in eight more, the cancers had shrunk. After an average of more than three years’ follow up, the researchers calculated that for patients like these, there was a noticeable, if not spectacular, boost in their odds of being alive four years out without further cancer growth — 36%, compared to just 24% in the patients whose cancers did not seem to respond to that second dose of engineered cells.’
The folks at Fred Hutch report :
‘The researchers found that patients’ cancers were more likely to shrink or disappear after the second dose when that second dose contained more engineered cells than they’d gotten the first time. And, patients tended to do better if T cells of a certain variety — “killer” T cells — multiplied to greater numbers in their bloodstream after the second dose of CAR T cells was dripped in.
Consistent with their previous research, the team showed that these killer T cells were more likely to multiply if patients had received a double wallop of two immune-suppressing chemotherapy drugs before their first dose of cells, weeks or months earlier. The researchers think that these patients’ immune systems likely never had a chance to mount a significant response against the foreign-looking CARs in the engineered cells.’
And this is where things become more complicated:
The lead researcher at Fred Hutch said, ‘There has been a lot of buzz around CAR T-cell therapy, but there still is a lot of work to be done. And we can’t just rest on our laurels. “We can’t take that for granted. There’s so much more work there.’
about the author
I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.