Thread by @VincentRK

10 years ago, Drs San Miguel, Merlini & I wrote that defining myeloma as myeloma only after end organ damage happened was like defining breast cancer as breast cancer only after metastatic disease occurred @NatRevClinOncol @mvmateos #MedTwitter nature.com/articles/nrcli…

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2/ We proposed redefining myeloma. The International Myeloma Working Group agreed after studies to validate proposed biomarkers was completed. The new diagnostic criteria was published in 2014 in @TheLancetOncol

It now the 2nd most cited paper in myeloma thelancet.com/journals/lanon…

3/ The updated criteria represent more that just the definitions outlined: it was a paradigm change that we can identify and treat myeloma before clinical end organ damage had occurred.

But the updated criteria applied only to 10-15% of patients who had smoldering myeloma.

4/ Even with the revised criteria, it is important to note that most patients with smoldering myeloma are still considered as having. smoldering myeloma.

5/Our current understanding of smoldering myeloma analyzing 40 years of published research is that it is not an intermediate biologic stage between MGUS & MM but rather a heterogeneous clinical entity in which one third have biologic malignancy & two thirds biologic premalignancy

6/ Current risk stratification efforts aim to identify the subset of SMM patients in whom malignant transformation has occurred but end organ damage has not yet manifest @mvmateos @SagarLonialMD @myelomaMD @BloodCancerJnl nature.com/articles/s4140…

7/ We are conducting clinical trials in patients defined as high risk smoldering myeloma. We are continuously trying to identify biomarkers that distinguish biologic premalignancy from malignancy, something that's not a big issue in most other cancers but is in myeloma.

8/ There are 3 types of randomized trials being pursued. It's a rare disease and we have to look at regulatory issues across the world not just the US in planning them as well as the varying research goals.

It will take many years for us to get clarity on the issues.