General MM

Key highlights from the ESH Clinical Updates meeting on Multiple Myeloma

We are delighted that the MM Hub team were able to attend the European School of Haematology Clinical Updates meeting on Multiple Myeloma, chaired by Hermann Einsele, Irene Ghobrial and Sonja Zweegman and held at the Marriot Rive Gauche Hotel in Paris, from 19th- 21st May. The meeting boasted record attendance from clinicians, as well as representatives from numerous companies. A wide range of topics were presented, but with the major focus on treatment regimens across the different MM patient subsets, there were several emergent themes.

One of the first topics addressed was that of cytogenetics, by Hervé Avet-Loiseau, from the Cancer Research Center of Toulouse and a leader in this field. Although the occurrence of several well-documented genetic abnormalities (eg. del(17p), t(4;14), t(11;14) del(1p32)) place certain MM patients in a high-risk category with poor prognosis, only a few other genetic markers such as TP53 mutations as well as NRAS and KRAS have emerged, despite much investigation. The general conclusion was that targeted exome sequencing with higher patient numbers is needed in order to further define prognostic values.

The benefit of triplet versus doublet therapies was discussed early on, with the consensus that the use of triplet regimens was more beneficial. Promising data from several of the recent clinical trials was presented and the benefit of such combinatorial regimes was emphasized. One of the clear messages –a point also highlighted later in the conference by Philippe Moreau, from the University Hospital of Nantes, was that monoclonal antibodies, and in particular daratumumab, will soon be a mainstay treatment in the relapsed and refractory setting in combination with current MM therapies. The benefit of monoclonal antibody therapy for newly diagnosed patients is understudied, and the need for more clinical trials in this patient set was agreed upon.

However, amidst therapeutic discussion, a notable point was that the high cost of many novel or experimental therapies limited availability to all, creating a potential divide between those that can afford them and those that cannot. Therefore, in these cases, it was hoped that patient access may be granted by establishing clinical trials or by clinicians requesting (or even pushing for) further experimental access of certain drugs.

The unique property of MM as a highly heterogeneous disease was heavily discussed, with a very clear ‘one size doesn’t fit all’ message. The need for patient monitoring throughout treatment to assess efficacy was clear, and the use of Minimal Residual Disease (MRD) as a progression factor is increasingly valued over other markers. Indeed, Ola Landgren from the Memorial Sloan Kettering Cancer Center, found that MRD negativity can better reflect disease free progression and he concluded his talk with the strapline: ‘MRD is more important than the treatment modality’.

Differences of opinion emerged in many areas but were healthily discussed. In particular, attendance by life-long clinician Bart Barlogie (from Mount Sinai) was well received, not only for his unconventional dress-sense, but for his insightful and challenging questioning of the speakers, along with reference to his own personal experiences over the years, which contributed to fruitful discussion. One of his many notable points was that there is too often an emphasis on achieving consensus in MM, for which, given its inherent heterogeneity, seems to be a misdemeanor. Indeed, it was agreed that sometimes you ‘just have to go for it’, which much of the anecdotal evidence presented also seemed to suggest. Much of Bart’s own anecdotal evidence was testament for this, in a culture that is perhaps becoming overly reliant on evidence based medicine for complete guidance. In general, it was agreed that clinicians perhaps need a bit of both, and that the ideal is evidence based medicine that can ultimately help tailor the patient treatment experience.

Much discussion centered around the concept of early intervention, and at what point exactly clinicians should interfere. It was suggested that the MM precursor condition of MGUS requires much closer monitoring as it could provide clues to identify patients at higher risk of progression to symptomatic MM. This transition phase was also the focus of a talk by Shaji Kumar, from the Mayo Clinic, who emphasized the point that early intervention could prevent the long-term end organ damage that can ensue once MM takes hold, and must be evaluated. Irene Ghobrial from the Dana-Faber Cancer Institute proposed that in this respect the unique property of MM, in having a well-characterized precursor state, should be taken advantage of. A program in which patients were ‘empowered’ to send samples themselves that could be used to screen for possible prognostic factors for progression from MGUS to MM, was outlined. Such a sheme could potentially circumvent the difficulty in obtaining a suitably large sample size. However, it was emphasized that many MGUS patients do not progress, and that harsh treatments, which in themselves could potentially cause long-term harm to the patient, should be limited unless absolutely necessary.

While early intervention was clearly a strong emerging theme, some of Bart Barlogie’s experience put him at odds with this, which he made clear in his statement: "I only shoot for a real enemy and then I use a Kalashnikov!" Therefore, the ongoing challenge for MM treating physicians is to further establish which Kalashnikov to use and to identify exactly when to use it, but I'm confident that those who attended the ESH meeting came away better armed than before to make that decision.