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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This year has been an unprecedented Grand Cru year for the field of multiple myeloma, with no less than four drugs approved by the FDA to date… the fourth one just this morning while writing this preview!
- Panobinostat (Farydak) in relapsed/refractory disease in combination with bortexomib plus dexamethsone after at least 2 prior therapies.
- Daratumumab (Darzalex) received accelerated approval based on phase 2 data and is human CD38-directed monoclonal antibody that is indicated for the treatment of patients who have received at least three prior lines of therapy.
- Ixazomib (Ninlaro) is the first oral proteasome inhibitor and is approved in combination with lenalidomide plus dexamethasone, in people who have received at least one prior treatment.
- Elotuzumab (Empliciti) is a monoclonal antibody against CS–1/SLAMF7 approved today in combination with lenalidomide plus dexamethasone after 1–3 lines of prior therapy.
There are also many promising new agents in development and quite a few that may well not make it to market as a result of newer, better tolerated agents coming through.
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