Is it possible for a myeloma patient to achieve a stringent complete response (sCR) and not achieve minimal residual disease (MRD) negativity following treatment?
Yes, it is possible for myeloma patients to achieve sCR and not achieve MRD negativity following treatment. The outcome of treatment in myeloma is defined using very specific standards based on the results of tests using blood and bone marrow samples. In the blood, an sCR is defined as having no M protein, no light chain, and no myeloma cells detectable. However, achieving an sCR does not eliminate all myeloma cells in the body. Conventional blood tests are not sensitive enough to detect any myeloma cells remaining after treatment, but MRD measurement in the bone marrow can. Tests such as flow cytometry or next-generation sequencing can detect one myeloma cell in 100,000 (105) or one million (106) normal bone marrow cells.
The opposite scenario may also be possible, that is, it may be possible for patients to be MRD negative and not have a sCR. The reason for this is that M protein can hang around in the blood for a while even after all the myeloma cells are gone. Also, if a patient has been treated with Darzalex, a monoclonal antibody, it can be detected in the blood similarly to M protein. There are additional tests that can tell if M protein detected after treatment with Darzalex is due to the drug or to the myeloma.
For more information about myeloma tests and interpreting their results, please view our Learn Your Labs High Impact Topic video here.
What is the status of quadruplet regimens for treatment of myeloma—are they better than triplet regimens?
Studies have looked at the potential value of adding a fourth agent to traditional three-drug combinations. There are only two quadruplet regimens approved for use in newly diagnosed patients with myeloma—based on phase 3 trials that compared the quadruplet to a triplet regimen; however both regimens are used mainly outside of the United States. Quadruplet regimens under investigation that have the potential to be used widely in the United States include Velcade-Revlimid-dex plus Darzalex or Sarclisa, or Kyprolis-Revlimid-dex plus Darzalex or Sarclisa. Although the initial data look promising with respect to response rates and depth of response, the main concerns with using a quadruplet regimen are increased risks of side effects and cost. Additionally, data do not show that a quadruplet regimen is any better than a triplet for patients with high-risk cytogenetics.
How do patients and clinicians decide between chimeric antigen receptor (CAR) T-cell therapy and bispecific antibody therapy?
Both treatments are good options for patients with relapsed or refractory multiple myeloma. There are two considerations to keep in mind that may help in deciding between either option. First, the availability of CAR T-cell therapy is an issue. Please see our FAQ posts here and here about the availability of the two FDA-approved drugs in this class. Second, patient preference should be a priority. For example, CAR T-cell therapy may be a good option if a patient and their doctor agree that the process of CAR T-cell therapy can be tolerated well (because this type of therapy is a bit more intensive than bispecific therapy); also, a patient may find the “one-and-done” treatment more attractive than ongoing therapy. Or, bispecific antibody therapy may be a good option for a slightly older or more frail patient.
To learn more about all the myeloma studies presented and highlighted from the 2022 American Society of Hematology meeting, please view our blog posts here, here, and here.