“Bispecifics are the prom queens of ASH”—Tom Martin, M.D.
Attending the virtual iteration of ASH has been a unique experience, in that I’ve had the opportunity to see many of the leading international myeloma experts all from the comfort of own home. One of the silver linings of a virtual symposium is that I have the option to watch presentations live and then watch them again on replay. I even have time to pour myself a cup of coffee or prepare a light meal throughout the learning. I must confess that I don’t miss having to dash from lecture to lecture through a crowd of hundreds of people. And while all of these new changes have been convenient for me, I’ve found that they have been much more convenient for my dog. She too has developed a heightened degree of separation anxiety as she finds herself coping with the lockdown. She loves virtual ASH.
I do, however, miss the feeling of solidarity between the IMF support group leaders during the in-person symposium. For as comfortable as I’ve been during this virtual experience, I’m finding that there is no real substitute for those in-person discussions and shared meals that bring us together as myeloma patients.
Every year we not only anticipate better treatments for myeloma, but we come to find new sources of hope. The immunotherapy developments for multiple myeloma is the highlight of this year’s ASH with new CAR-T cell regimens and bispecifics (BiTEs). Dr.Tom Martin from UCSF characterizes the bispecifics as the prom queen of this year’s ASH. T-cell bispecific antibodies (bsMabs) are capable of binding two different antigens that are engineered to bind a T-cee (cytotoxic cell) and a myeloma cell. The T-cell then causes apoptosis or cell death of the myeloma cell. The advantage of bispecifics is that they are an “off-the-shelf” therapy and have the potential to treat myeloma patients that are triple and penta-refractory to previous lines of therapy. These patients may have failed immunomodulators (IMiDS), proteasome inhibitors (PIs), and anti-CD38 antibodies.
With bispecifics, the cytokine release syndrome (CRS) may be limited as compared to the CRS noted with CAR-T cell therapy. They may also be available in the community as opposed to having patients travel to tertiary centers where T-cells can be harvested and engineered in a process that may take four to eight weeks. These new BiTEs include Teclistamab, Talquetamab, AMG70, and REGN5458 which are all directed to the BCMA site on the myeloma cell. Cevostamab is a novel BiTE that binds FcRH5 on the meyeloma cell and binds to the CD3 site on the T-cell. These are early phase studies that have small numbers of patients but they suggest the direction of immunotherapy for patients that have no other options.
Another class of immunotherapeutic agents include the newly approved antibody-drug conjugates (ADC), such as belantamab mafodotin (Blenrep). This drug is now being prescribed in relapsed refractory multiple myeloma. A new ADC that has been presented in this meeting is MED12228, which shows promising results in a small study. Manageable side effects of this class of drugs include ocular toxicity.
These drugs may indeed prove to be crown-worthy and I will be awaiting further trials with a larger cohort of patients.