The title of this post seems to be just a mumbo-jumbo of abbreviations that beg the question as to what all of it means and what its significance is. Well, it hides several developments that should be of interest to us, myeloma patients. So, let’s pick the title apart and get to the bottom of things.
RMAT is shorthand for ‘Regenerative Medicine Advanced Therapy’, a program established under the ‘21st Century Cures Act’ of 2016’ to expedite the development and review of promising pipeline products for life-threatening diseases. Drugs/treatments are eligible under this program if they meet several standards:
The grant of RMAT status by the Food and Drug Administration is quite a big deal as Federal records indicate that, since this program’s inception, more than half of the requests submitted by the pharmaceutical industry for RMAT designation have been denied.
Allo-715 is an ‘allogenic’ (donor) CAR-T product that targets the protein BCMA on the surface of myeloma cells. The product is being development by the California based company Allogene Therapeutics. An allogenic CAR-T product (also known as ‘off-the-shelf’ CAR-T) is different from the recently approved ide-cel CAR-T for multiple myeloma developed by Bristol-Myers/Celgene or the Johnson & Johnson cilta-cel CAR-T that is currently under review by FDA. Ide-cel and cilta-cel are based on the T-cells harvested from severely sick myeloma patients whereas Allo-715 is manufactured from the cells of healthy patients.
There are several advantages to allogenic CAR-T products, such as:
Since we are talking here about donor-based product it is more than reasonable to ask whether the administration of Allo-715 may trigger Graft-versus-Host (GvHD) reactions/side effects that occur frequently with treatments such as allogenic (donor) stem cell transplants that may be used to treat aggressive and/or high-risk myeloma. The answer is that this is a valid consideration that has been/is being addressed by Allogene. Every CAR-T treatment requires lymphodepletion (the destruction of T-cells and lymphocytes prior to immunotherapy). The drugs typically used as part of the CAR-T process are Cytoxan (and many of us are familiar with this one) and fludarabine. The Allo-715 program calls for the addition of a third compound, also discovered by Allogene called Allo-647. This drug is a monoclonal antibody that is designed to suppress the host immune system to allow Allo-715 to stay engrafted in order to achieve its full therapeutic impact.
The company has reported early results from part of their Phase I clinical program. Phase I studies are designed to understand the safety of the product and to also pin down the ‘optimal’ therapeutic dose (efficacy). These results can be summarized as follows:
(At the expected therapeutic dose of 320 million cells)
All in all, this is an interesting development to monitor over the next two or so years. Allogene still has a way to go as they need to finish up the full Phase I program and move on to an expanded patient pool in their Phase II/III clinical development. As such, we have no certainty that this combination of products will ultimately come to market though we do have a fair amount of information to be cautiously optimistic that, in the not-too-distant future, we may see this product in clinical use as another treatment option for us when things start to come off the rails.
Those interested in this clinical trial can find it here.
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.