Shining a light on hidden gems in the myeloma niche
If we want to go beyond the proteasome inhibitors, IMiDs and anti-CD38 antibodies in multiple myeloma, there are plenty of emerging candidates these days.
This is excellent news, but how will it all fit together, and which gems were under-rated at the recent ASH meeting?
The latter may catch a few people by surprise when the clinical aspects are considered in the totality of what needs to be done and in which patient subsets.
We discuss near and medium term aspects, which may have a lasting impact and also talk about why they matter.
To find out, the final part of our myeloma mini-series offers an engaging and thoughtful fireside chat with a global thought leader in this niche…
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Happy New Year!
Immunotherapy treatment for multiple myeloma has been around for several decades, first in the form of stem cell transplantation, then augmented by the addition of IMiD immune modulation drugs such as thalidomide, lenalidomide or pomalidomide. In due course, along came immune checkpoint blockade in solid tumours and it was only a matter of time before they would be evaluated in hematologic malignancies, albeit with mixed results.
The proteasome inhibitors and IMiDs are unlikely to go away any time soon, but other targets have also emerged including CD38, SLAMF7/CS1, BCMA/APRIL, PD–1/L1 and a few others that are being currently investigated in the clinic.
Where does this leave us and what looks really promising?
In our latest thought leader interview undertaken at the recent American Society of Hematology (ASH) meeting in Atlanta, we asked a global expert for his candid views and were not surprised at some of the hard hitting comments that emerged from the in-depth discussion of several key issues…
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After regularly reporting here at BSB on several readouts in terms of antibodies and CARs since ASH last year, it’s reasonable to conclude now that there has been growing interest in BCMA–APRIL as a target in multiple myeloma (MM). The CAR T cell therapies have generally focused on BCMA or BCMA-TACI as a target, while antibody approaches such as Aduro’s, BION–1301, target APRIL.
T cells attacking a cancer cell
These new therapies have all been either preclinical in nature or preliminary phase 1 studies in a very limited number of patients, meaning that the best we can characterise them is that old reliable chestnut, ‘promising but early’… to do otherwise would be rather extravagant and hopeful at best.
Given the data from several CAR T cell therapy studies were being presented at two meetings on two separate continents only a few days apart, it makes sense to review them as a whole.
It’s therefore time for a detailed update, including a review of the differences in the key studies, a look at where we are now, as well as tips on what to look for going forward.
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The AACR Poster Halls get packed quickly!
It’s time to change direction and take a look at some of the Gems from the Poster Halls at the recent American Association for Cancer Research (AACR) meeting.
One particular abstract that looked interesting related to the Aduro compound, BION–1301, which is a monoclonal antibody targeting the B cell Maturation Antigen and its ligand, A Proliferation Inducing Ligand (BCMA-APRIL) in multiple myeloma.
Increasingly, there has been a lot of clinical interest in the BCMA target, but what about APRIL?
We spoke to one of the scientists involved in the research about this novel agent:
“It is very effective at abrogating the activity of APRIL and, in particular, in our models blocks the growth, survival, drug resistance, migration and adhesion of myeloma cells both in-vitro and in-vivo in our murine models. These models have been predictive for clinical activity of other novel targeted therapies including lenalidomide and bortezomib, and so we think targeting APRIL represents a very promising strategy.”
Sounds pretty good, right?
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