Just a few years ago we'd think of Immunotherapies and speak about treatments such as IMIDs (thalidomide, lenalidomide, pomalidomide) and anti-CD38 monoclonal antibodies (daratumumab or isatuximab). Then CAR-T cell therapies, ADCs (Antibody-Drug Conjugates e.g. BlenRep) and bispecific antibodies took center stage and were described as anti-BCMA (B Cell maturation antigen) directed therapies.
Now, in July 2021, given the expansion of targets on myeloma cells (e.g. GPRC5D and FcRH5) we are now talking about the broad new class of treatment called "T Cell engagers", the two leading types being CAR T cells and bispecific antibodies.
If you're reading this and wondering why these immunotherapies are generating so much buzz, the answer lies in the ORR (Overall Response Rate) and DOR (Depth of Response) as compared to what we were seeing before their arrival.
As Dr. Noa Biran stated at a recent Myeloma Crowd RoundTable Webcast: "After three relapses of standard therapies (IMIDs/PIs/Anti-CD38 antibodies), efficacy of new therapies are about 30%." By this she means new drugs like selinexor, melflufen, targeted inhibitors and others. (watch her comment at 41:53 in Dr. Biran's video).
T cell engager therapies are producing an overall response rate anywhere from 55% - 100%, and minimal residual disease (MRD) negative results are being seen in patients who are even refractory to 5 lines of therapy (i.e. resistant to two types of IMIDs, two types of proteasome inhibitors and one anti-CD38 monoclonal antibody). This has never been seen before. While the duration of response for CARs is not all we'd want and we have less data on the duration of response with the bispecific antibodies, these therapies are being improved as you read this.
We are witnessing the reinvention of myeloma treatment.
Most fundamentally "bispecific antibodies, offer a treatment alternative that may be better suited for myeloma patients who either can't wait for expansion of their T cells or for less fit patients, as there is an overall lower incidence of Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) than seen with CAR T therapies."
Dr. Surbhi Sidana used this slide from ASH 2020 in her ASCO 2021 summary discussion of CAR T and bispecific antibodies to offer a basic comparison of these options.
Note: Some of the statistics will have changed. It is also important to remember when you compare efficacy of a CAR T product to a bispecific to request the overall response rate for the dosage that has been determined to be the most effective for Phase 2 trials (RP2D) for that bispecific. Some of the percentages you'll see include lower doses in dose escalation studies.
For more detailed data out of ASCO 2021 on Cilta-Cel CAR T therapy and leading BITE therapies teclistimab, elranatamab and talquetemab see the links below:
Here is another chart I find very helpful in thinking about advantages and disadvantages of CAR Ts and bispecifics.
It's important to recognize that all but one CAR T (Abecma by Bristol Myers Squibb) and all bispecific antibody options are only available in a clinical trial and they are not easy to get into. For this reason, in the most recent Myeloma Crowd Round Table Dr. Morie Gertz, and Dr. Noopur Raje agree that if you get offered a spot in a trial, "Take It!"
Lastly, in my experience as a Myeloma Coach I've learned that people find it helpful to have a checklist to discuss with their Myeloma Specialist. Here's one to get you started. Please add your own questions.
We will continue to learn more as additional data comes out and as myeloma investigators gain more experience with both CAR T and bispecifics, but the treatment world in myeloma is changing and we look forward to the promise and hope of these new therapies.
about the author
Bonnie Falbo
Bonnie is a Myeloma Coach and the caregiver for her husband with Multiple Myeloma. They live at the foot of the Blue Ridge Mountains in Afton, VA with their 2 dogs and 2 cats.
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