This is not quite a multiple myeloma article, but still good to know …
I am quite certain that over the past week many of us have seen the blizzard of press mentions of the early results of the investigational anti-BCMA CAR-T product bb2121 (Bluebird-Celgene) in MM patients published in the New England Journal of Medicine , that has created excitement ranging from tempered to very excited, depending on the source of comment. But that is not what this article is about.
It is unquestionable that much still needs to be learned about CAR-T treatment, especially why some patients respond very well and other don’t. An interesting article was published in the Journal of Clinical Investigation this past week that was drowned out by the above mentioned article. This latter article summarizes research that has been undertaken with Kymriah (Novartis), the first FDA approved CD-19 target CAR-T to treat pediatric Acute Lymphoblastic Leukemia (pALL), to understand WHY some patients achieved remission but others didn’t or why some patients had a durable response and others a transient response. OK, this is not about MM but let me suggest that you don’t stop reading, because we are seeing similar outcomes/issues in the clinical trials for CAR-T products in MM.
Kymriah targets the protein CD-19 that is found on the surface of a variety of cells. The engineered T-cells will latch on to this protein and will kill the cell that expresses this protein (and that may be a cancerous or a non-cancerous cell). Be aware or reminded that quite a few other proteins are also present on cell surfaces and may present other targets for engineered T-cells. [And that is why the whole host of CAR-T clinical trials currently in progress are aimed at a variety of these surface proteins, such as BCMA or other ‘clusters of differentiation’ – the ‘CD-numbers’ that we read about. Other trials target different combinations of surface proteins to give us, e.g. bi-specific CAR-T’s, or anti-BCMA + some CD-# CAR-T’s.]
Specifically relating to Kymriah, used in current clinical practice, is was found that the success of patient outcome depends highly on the magnitude of the presence (or lack thereof) of several different surface proteins, both in the original T-cells harvested from patients and in the expanded T-cells engineered in the lab. For those interested in the details (and who are willing to go through some rough reading, click on the second link provided earlier).
My personal take-away from the article is simple: researchers are starting to define very specific (and in some cases quantitative) factors about the make-up of our cells that are a solid prognostic marker as to whether a given CAR-T product/treatment may or may not be successful for a given patient. With the treatment cost for CAR-T ranging between $ 500,000 to $ 1 million [depending on the complications encountered following CAR-T infusion] it is safe to assume that, in the future, patients will be screened early on to determine whether they will be good candidates or not for treatment [OR, that payors/insurers will start demanding such screening to avoid a large outlay of funds for a treatment that may, most likely, not be unsuccessful]. Be prepared (again my very personal opinion) that, in the future, CAR-T will NOT become available to anyone who wants it, regardless of whether the treatment program is for pALL, MM or other hematologic or solid tumor malignancies.
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.