New data in the diagnosis and prognosis of multiple myeloma

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Published: 3 Apr 2013
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Prof Paul Richardson, Prof Phillippe Moreau, Prof Jesus San Miguel, Prof Gareth Morgan

Prof Paul Richardson, Prof Phillippe Moreau, Prof Jesus San Miguel and Prof Gareth Morgan join together for ecancertv for this expert panel discussion filmed at the 14th International Myeloma Workshop (IMW 2013), 3-7th April looking at understanding of new data in the diagnosis and prognosis of multiple myeloma.  

Pomalidomide and carfilzomib have recently been approved in the US for treatment of multiple myeloma (MM). Pomalidomide was approved on the basis of two Phase II trials. A robust response of approximately 30% was seen in both studies in double refractory patients, with durability of response and impressive progression free survival (PFS) and overall survival (OS).

In both trials, a predictable and manageable toxicity profile was observed. This drug represents a significant advance in the treatment of MM. Combination studies (with bortezomib and carfilzomib) and subgroup studies are underway. Carfilzomib received accelerated approval last year with low dose dexamethasone as a premedication and now in combination. It has shown clear activity in the context of double refractory relapse disease. Carfilzomib is associated with relatively low rates of neurotoxicity. There are other toxicities, although these are believed to be generally manageable.

The oral proteasome inhibitor, MLN9708, has shown favourable tolerability. Its activity in combination also appears to be encouraging. However, it does not seem to be as potent as IV or SC bortezomib.

Treatment of high risk smouldering myeloma is a key topic at this year's IMW. Smouldering myeloma is a very heterogeneous group of patients, as it also includes MGUS patients who have a very low rate of progression to MM. At the other end of the spectrum are the high risk patients for progression, sometime referred to as 'early myeloma', most of whom will progress to full-blown MM in 2-3 years. Recent Spanish data has shown that thalidomide and dexamethasone in combination can delay the progression to MM, and improve the OS in this group of patients.

Myeloma is not only a heterogeneous disease between individual patients, but also within an individual patient. There is more than one subtype of malignant cell, which has important implications for treatment. At any one time during the disease, a single subtype of clone can be dominant.

This has been termed the 'clonal tide' in MM. Because of the changing face of MM over the course of the disease, it is thought that a patient showing initial resistance to a therapy who then relapses can subsequently show sensitivity to this treatment again, as the clonal pattern of their disease changes. It is now possible to track the presence of clones over time and it may be possible to develop a myeloma tool based on next generation sequencing to use in biopsies to monitor the clonal content and intervene early before the clone has become too complex.

Several monoclonal antibodies have been investigated in MM in combination with lenalidomide and dexamethasone. Further studies are underway.

The assessment of minimal residual disease (MRD) should be assessed both inside the bone marrow and outside the bone marrow. Outside the bone marrow, imaging techniques such as PET scan should become the gold standard. In the bone marrow, there are two imaging techniques available. The first of these is molecular imaging and the second is multiparameter flow cytometry (MFC). The latter is more applicable for use in routine laboratories.

A combination of both extramedullary and intramedullary assessments would provide the best tool to help decide on therapy in the future. Currently, studies have shown that a positive MRD can help guide consolidation and maintenance therapy.

Bisphosphonates are used routinely in MM patients. A recent study on zoledronic acid has shown that the use of zoledronic acid not only reduced bone disease but improved survival in the patients treated. This is the first time a survival advantage has been seen with supportive care. As a result, guidelines now recommend the use of zoledronic acid until disease progression occurs.

This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).