The non-transplant eligible patient

Danielle Barron speaks to Dr María-Victoria Mateos, who is an Associate Professor of Haematology and Consultant Physician at the Haematology Department at the University Hospital of Salamanca.

What type of patient is not eligible for a transplant?

This question is difficult and challenging because from the theoretical point of view, transplant is a procedure available for all patients with MM. However, in the practice, I would say that newly diagnosed myeloma patients older than 70 years are not eligible for transplant. Patients between 65 and 70 may or may not be eligible for transplant depending on frailty score, performance status and cardiac and pulmonary function.

Does this make treatment more difficult?

I don’t think so. In the past, the role of transplant was relevant because this was the strategy that made possible to prolong the duration of response and survival of patient who were candidates to receive it. This meant that patients who were not candidates for transplant experienced a short duration of response and an overall survival not superior to two years. However, after the introduction of novel agents, especially proteasome inhibitors such as bortezomib and carfilzomib, and immunomodulatory drugs such as lenalidomide and pomalidomide, the options of therapy for this population not eligible for transplant are very effective, with a good safety profile and minimal impact on the quality of life. Finally, they are contributing to prolong the duration of response and the overall survival of this population doubled over the last years. This benefit is increasing more and more because the monoclonal antibodies are going to be incorporated to the first line of therapy.

What is the overall treatment strategy in terms of goals, duration, etc?

The overall goal of the treatment would be the cure but as we are not able to identify the patients who are candidates to be cured at the time of new diagnosis we have to use surrogate markers in order to predict length of progression-free and overall survival. Today we know that maximal eradication of the tumour clone is required to achieve these objectives and the achievement of the minimal residual disease negative is becoming the main objective to reach with each treatment regimen we plan for our patients with myeloma. In order to follow this objective, the International Myeloma Working Group recently updated the response criteria incorporating this new category, minimal residual disease negative that we have to evaluate inside and outside of the bone marrow. For the evaluation of the minimal residual disease into the bone marrow we can use either flow cytometry or next generation sequencing; in summary, both are able to detect one malignant plasma cell within one million of normal cells so the sensitivity level is important. For the evaluation of the minimal residual disease outside of the bone marrow we use PET-CT and although it is less standardised than flow and next generation sequencing, it is very important because some patients with myeloma present with extramedullary disease (an uncommon manifestation in multiple myeloma).

What kind of prognosis is there for patients nowadays?

There are different prognostic classifications: International staging system or the revisited international staging system that considers levels of albumin, beta-2 microglobulin, lactate dehydrogenase (LDH) and the presence of cytogenetic abnormalities. Both systems allow us to identify three different subgroups of patients with different prognoses so the information is very valuable for both physicians and patients.

It is true that most patients with myeloma are at standard risk but approximately 20-25% of patients with myeloma can present with high-risk features. It is critical the identification of these high-risk features at the moment of diagnosis because we know that these patients respond well to the treatment; however, the duration of the response is usually very short so it would be necessary to establish therapeutic strategies a bit different in order to maintain the response achieved.

Should a patient be disappointed they are not eligible for a transplant?

I think this should not occur today in 2018 because of all arguments I explained before. The outcome of patients not eligible for transplant has significantly improved after the introduction of novel agents-based combinations and there are even some young patients transplant eligible that they don’t want to receive the transplant.

There are, in fact, some studies ongoing trying to evaluate if with the novel agents-based combinations there can potentially be a subgroup of patients in which the transplant is not necessary to get the same outcome than patients who receive it.