- What is the best treatment for newly diagnosed myeloma patients with high-risk disease?
Based on expert opinion and clinical data available, the current standard of care for initial treatment of patients with high-risk myeloma is to use the combination of Kyprolis (carfilzomib)-Revlimid (lenalidomide)-dexamethasone—also referred to as the KRD regimen. Also, if health insurance approves its use, some doctors will add Darzalex (daratumumab) to the KRD regimen. The goal of treatment for patients with high-risk myeloma is to achieve a complete response and minimal residual disease (MRD) negativity (if possible). Doctors will closely monitor high-risk patients during initial treatment because if patients don’t achieve a response after two cycles of treatment, doctors will need to switch to a different treatment regimen. In high-risk patients, doctors won’t wait too long for a response. Treatment for patients with high-risk myeloma needs to be continually optimized to ensure the deepest response to treatment.
Following initial therapy, treatment with an autologous stem cell transplant (ASCT) occurs (in those patients who are eligible) followed by maintenance therapy with a proteasome inhibitor (such as Kyprolis or Velcade [bortezomib]) and Revlimid. For patients who are ineligible for an ASCT, a similar treatment approach is taken as described above. Again, the goal is to achieve the deepest response possible and optimize therapy to achieve that goal.
- If patients have had stem cells collected for use for their autologous stem cell transplant (ASCT), can these same stem cells be used for CAR T-cell therapy?
Unfortunately, no, stem cells collected for ASCT cannot be used for CAR T-cell therapy. Each therapy requires different cell populations. The cells collected for ASCT are known as CD34+ stem cells and they contain a very low number of T cells—and, as its name implies, CAR T-cell therapy requires T cells.
Also, it is unknown how long T cells remain alive and useful in the stem cell population collected for ASCT.
- What is the difference between a bispecific antibody and a bispecific T-cell engager (BiTE)?
Bispecific antibodies are a type of monoclonal antibody therapy. Bispecific antibodies are made from pieces of two different antibodies that have been fused together, so that one piece binds to myeloma cells and another piece binds to T cells. The bispecific antibody brings together the myeloma cell and the T cell so that they are in close enough proximity that the T cell can kill the myeloma cell. A BiTE is a type of bispecific antibody and BiTEs are made from two antibody fragments that have been fused and they do the same job as the bispecific antibodies. Preliminary data from phase 1 clinical trials show that 50% of patients or more respond to treatment with bispecifics and BiTEs.
- Do cytogenetic abnormalities change during the course of disease (for example, will the abnormalities present at diagnosis be the same at first relapse)?
Yes, changes in cytogenetic abnormalities can occur over time. After initial treatment some cells may be left behind that are not killed by the treatment (even in those patients with a complete response). The cells left behind will be the ones that will grow and cause relapse. These cells will have cytogenetic abnormalities that are different from the ones at diagnosis. As a result, it is possible that some patients who had standard-risk cytogenetic abnormalities at diagnosis may gain high-risk abnormalities at relapse. Knowing what the abnormalities are at relapse will help with subsequent treatment choices. That is why your doctor will want to conduct another bone marrow biopsy at the time of a relapse.
