Targets in myeloma are interesting and hopeful for our futures as bispecific antibodies continue to become a key treatment option.

Using the immune system to fight multiple myeloma makes great sense to me. It’s exciting to follow trials targeting BCMA as part of the multiple myeloma treatment for the past few years. However, when/if BCMA is no longer a target for some patients, what’s next? There are additional targets and here, I’ll focus on Talquetamab, a T-Cell bispecific antibody targeting the novel antigen target GPRC5D.

Talquetamab as you can see above is “first-in-class, off-the-shelf, T-cell redirecting bispecific antibody and is directed against a new antigen target called GPRC5D.” This is exciting as it binds to the myeloma cell with the receptor GPRC5D (change from BCMA receptor). If you look at the above slide, Talquetamab is the green and orange antibody that binds to the T-cell and brings it to the myeloma cell which is close by in the bone marrow and then enhances killing the myeloma cell. This is the basic principle of bispecifics.

If that’s not exciting enough, the Overall Response Rate (ORR) for Talquetamab is 64-70% with weekly and once every 2 weeks dosing. This study is called MonumenTAL-1 (TAL for talquetamab). Please also note that a cohort of patients with prior CAR-T cell or bispecific antibody treatment were included. This demonstrates that talquetamab can work for patients that previously received a BCMA directed therapy and a refractory population. Great News!

If you look at the MonumenTAL-1 ORR and Duration of Response (DOR), it’s not a striking dose response, and some side effects, but if you go to a lower dose, you have flexibility to adjust the dose related to side effects. The blue line is DOR: right around 9 months. Important durable responses.

Additionally, Talquetamab can be combined with other agents to get even better response. In those with prior T-Cell redirection therapy, a 63% response rate with prior therapy. Lots of excitement with this change in targets (GPRC5D).

It is exciting to see the direction of different targets. The myeloma treatment landscape is constantly changing with new mechanisms of action (new ways to fight myeloma!)

With that, for this blog about change I’ve selected this song:

John Waite / 1982 / “Change”

ENJOY! Change can be a good thing!

Michael Tuohy

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