We think that not only for the high-risk patients, but for the whole group of patients who are transplant-eligible and newly diagnosed with myeloma, that there will be a new standard in the future coming from VTd, or the regimen of bortezomib, lenalidomide (Revlimid), dexamethasone (VRd), or other triple-drug combinations going to a 4-drug regimen, including daratumumab, will eventually become the new standard of treatment.
It’s too early to do that right now because we are waiting for the results of the second randomized part of the study that involves daratumumab as a maintenance therapy. However, based on the first part of the trial, we have submitted data to the regulatory bodies. My assumption is that, like in the older patients, adding daratumumab will become a standard for the initial treatment of patients.What impact could the combination of daratumumab and VTd have on the community oncologist if it is approved?
The big question is whether we will have approval to use daratumumab in the first-line setting, not only in the elderly, but also in the transplant-eligible patients.
Once the combination [is approved] it offers the unique opportunity for a high response rate, for long-term PFS. Therefore, I expect that it will be popular in the community setting. Patients will enjoy a long disease-free period, with a good quality of life—maybe going back to work and enjoying life—which is important. Daratumumab adds to the common standard of treatment.Did the study findings strengthen the case for finding the right combination of treatments?
This is one of the new options. Currently, we are running another study in the European Myeloma Network of D-VRd, which is highly comparable with the CASSIOPEIA trial. However, VRd is a more effective regimen than VTd. We consider this an upgrade of the original treatment with daratumumab.
Also, other combinations are undergoing investigation including isatuximab, which is another CD38-directed antibody [in] the ICARIA-MM study in the relapsed setting.
We probably have a new standard here, from diagnosis through the different stages of the disease and treatment.What are the next steps in research?
We need to look closer at the issue of retreatment. If we treat patients upfront with daratumumab, at a certain stage they will stop their treatment. If they progress or relapse, can we treat them again with daratumumab to the full benefit of the drug? Or, should we switch to another antibody like isatuximab or elotuzumab (Empliciti)? There are many others.
Then, the important issue is that we treat as many patients [as we can] with daratumumab in the first-line setting. This is the priority. The relapsed setting is also a valuable place for daratumumab, but it should not be our first goal. What we don’t know yet is how this treatment compares with other [monoclonal antibodies] and if we can combine with other [monoclonal antibodies].
<<< 17th International Myeloma Workshop
- Sonneveld P, Attal M, Perrot A, et al. Daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (NDMM): subgroup analysis of high-risk patients (Pts) in CASSIOPEIA. Presented at: 17th International Myeloma Workshop; September 12-15, 2019; Boston, MA. Abstract OAB-003.
- Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29-38. doi: 10.1016/S0140-6736(19)31240-1.