There are many factors that you have to consider. So first I consider if the patient is generally considered transplant eligible or not transplant eligible. This can be done based on several factors. One factor that we commonly use but which is not a perfect measure is age. Usually patients above 70 years are considered transplant ineligible but it depends on the individual fitness and comorbidities of the patients and also the wishes of the patients, so if they would consider transplant a potential option for themselves. This has also to be discussed in light of the changing treatment landscape that we have where we get more and more quadruplets incorporated also for elderly patients, including a CD38 antibody.
Other patient-related factors that I consider when choosing the optimal regimen are comorbidities, for example diseases of the heart or diabetes are important to consider, but also if there is already an existing neuropathy and how advanced these diseases are. Other important factors that we have to consider are disease characteristics, so is there a high-risk disease, is there a high need to start an urgent treatment or do we have some time to think about potential options or clinical trials? Of course, if the disease has a high risk status, for example deletion 17p, or also a high tumour burden.
All these factors have to be taken into account and have to be discussed with the patient. In the end we also have only the options available that the regulators give to us. So as of now this is for most transplant eligible patients a combination of daratumumab plus bortezomib and thalidomide and dexamethasone or daratumumab in combination with bortezomib, lenalidomide and dexamethasone. For some instances we can also use daratumumab or isatuximab with carfilzomib and lenalidomide and dexamethasone although this is not officially approved in Europe or the US. But, for example, in Germany we have the opportunity to ask the insurances to provide this to our patients.
In the context of autologous stem cell transplantation, how do you determine the best timing for transplant in the treatment sequence for NDMM patients?
As of today I have a quite clear answer. I would say we should do transplant if the patient is transplant eligible immediately after induction therapy. This means, based on the regimen that you’re using, that you usually give 4-6 cycles of induction treatment and then really do the stem cell collection and the stem cell transplant.
For most patients I would say a single transplant is enough, there are only a few occasions where I decide to do a tandem transplant. After this I usually do a consolidation treatment if this is approved in the respective country, for example in Germany we have the approval to do this, and I would not defer transplant at the moment.
How do emerging therapies like monoclonal antibodies and CAR T-cell therapies influence the treatment landscape for transplant-eligible NDMM?
They will definitely impact the treatment landscape, the question is when we will have the first convincing results on these new therapeutics, especially CAR T-cells and bispecific antibodies and whether they can really challenge transplant or even lead to the situation that we omit transplant in transplant eligible patients.
Many trials enrolling, for example the CARTITUDE-6 trial, will challenge transplant again. I’m curious to see in the next years how the results will look. But certainly it will take some time for these trials to read out since the benchmark is set very, very high with the introduction of the anti-CD38 monoclonal antibodies in the induction and consolidation treatment and also maintenance treatment in patients with newly diagnosed multiple myeloma that receive a stem cell transplant.
