ASH 2018 Is An Amazing CAR show! Chimeric Antigen Receptor (CAR)
It is interesting to note that just 10 years ago in 2009 there was just 9 CAR T abstracts in a total of 5176 total abstracts presented at ASH 2009. It has also taken 10 years to get just two FDA approved CAR T treatments approved. However for ASH 2018 there are 423 CAR T abstracts or 47 times as many. As can be seen in the following graph the growth has been exponential. It takes between 10 and 15 years to bring a drug from lab to clinic, so we can hope new CAR T approvals will also be exponential.
CAR T seems to be a recent development, however it has been well over 10 years in the making. There has been a lot of excitement around CAR T, but as can be seen from the growth in abstracts, this looks to be just the tip of the iceberg! New trials with multiple antigens targeted are being developed, as are many more antigens being identified as targets. Not to be left behind, multiple myeloma has had a similar explosion in the number of new abstracts.
As you might remember, myeloma represents just 1.8% of all cancers and historically has had more than its share of the new drugs which have been developed. The same holds true for the percentage of myeloma CAR T abstracts. Of the 423 CAR T abstracts, 104 of them are myeloma CAR T abstracts, or 25% of the total. This represents 14 times as many abstracts as one might expect based on the myeloma patient volume.
Recently Dr. Vincent Rajkumar recently presented a listing of 8 CAR T abstracts which he found of interest. Dr. Rajkumar is one of the finest myeloma specialists, and his focus on CAR T helps to signify how very important this targeted treatment has become for the future of myeloma treatment.
His list is below and it you CLICK on the Abstract Number it will go directly to the ASH abstract.
1) Abstract 955 - Updated Analysis of a Phase 1, Open-Label Study of LCAR-B38M, a Chimeric Antigen Receptor T Cell Therapy Directed Against B-Cell Maturation Antigen, in Patients with Relapsed/Refractory Multiple Myeloma
Update of known CAR-T LCARB38M: results look similar to Celgene's bb2121 with median progression free survival of 15 months. We need more follow up to know what percent of patients have enduring responses.
2) Second generation BCMA CAR-Ts - for want of a better term: All show promising activity. Problem is going to be how they make it to FDA approval.
Abstract 956 - Durable Remission Achieved from Bcma-Directed CAR-T Therapy Against Relapsed or Refractory Multiple Myeloma
Abstract 1012 - Efficacy and Safety of P-Bcma-101 CAR-T Cells in Patients with Relapsed/Refractory (r/r) Multiple Myeloma (MM)
Abstract 960 - Low Dose of Human scFv-Derived BCMA-Targeted CAR-T Cells Achieved Fast Response and High Complete Remission in Patients with Relapsed/Refractory Multiple Myeloma
Abstract 959 - Clinical Responses and Pharmacokinetics of MCARH171, a Human-Derived Bcma Targeted CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma: Final Results of a Phase I Clinical Trial
2b) Abstract 1011 - Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma
Defined CD4 CD8 composition BCMA CAR-T: Interesting idea. Not sure if there will be a real advantage. Need more data to decide.
3) Abstract 1009 - Tandem Autologous Transplantation and Combined Infusion of CD19 and BCMA-Specific Chimeric Antigen Receptor T Cells for High Risk MM: Initial Safety and Efficacy Report from a Clinical Pilot Study
Combined CD19 - BCMA CAR-T: another interesting idea and may overcome some resistance pathways.
4) Abstract 1014 - Safety and Efficacy of Multiantigen-Targeted T Cells for Multiple Myeloma
Multi-antigen targeting CAR-T: one step further than dual CD 19 BCMA targeting CAR-T. Interesting and may be another way to overcome resistance.
5) Abstract 591 - ALLO-715, an Allogeneic BCMA CAR T Therapy Possessing an Off-Switch for the Treatment of Multiple Myeloma
Allogeneic CAR-T - May fulfill potential of off the shelf CAR-T in future preclinical study.
6) Abstract 590 - NKG2D-CAR Transduced Primary Natural Killer Cells Efficiently Target Multiple Myeloma Cells
CAR-NK: I guess this is CAR-Tish and can be included in this list! This uses a CAR technology with natural killer cells instead of T cells. This will also be off-the-shelf.
7) Abstract 1013 - T Cells Expressing Anti B-Cell Maturation Antigen Chimeric Antigen Receptors for Plasma Cell Malignancies
Theres one more CAR-T abstract I found interesting but didnt know whether it was a Second generation CAR-T or a consecutive patient series with an existing CAR-T.
Thank You Dr. Rajkumar for your leadership in the patient fight to survive this deadly disease.
Another new treatment approach which is becoming more and more important is the use of Antibody Drug Conjugates(ADC). I plan on providing a similar evaluation of this very important new treatment approach in my next ASH 2018 Myeloma Crowd article.