Part 1:
Why does depth of response matter in NDMM?

Maria-Victoria Mateos, MD, PhD
University Hospital of Salamanca, Spain


I will address the relevance of depth of response in newly diagnosed myeloma patients. And here you can see my disclosures and while the first question that we can address is, why does depth of response matter in multiple myeloma? If we go how the myeloma treatment evolved over the last year, especially during the recent century, we had the opportunity to see how many new drugs emerged and were introduced in the treatment of our patients with multiple myeloma. With all the many new drugs, we moved immediately to three- and maybe we are moving to four-based combinations. When we focus on newly-diagnosed myeloma patients, we realize that almost all of our patients respond to the first line of therapy, because the overall response rate is over 90% for almost all combinations.

When we evaluate in-depth the quality of the response and we evaluated the complete response rate, we can say that maybe around 50% of our newly diagnosed myeloma patients can achieve complete response with these new combinations. And we know that CR is an important surrogate marker, predicting PFS and even OS and this is a classical study coming from the Spanish Myeloma Group, showing how the complete response rate translated into a significant benefit in overall survival. This study was done in the conventional [inaudible]. But we also realized that when we consider just the complete response, while it is an important surrogate marker, but the patients achieving CR did not result in a plateau-phase and neither in terms of time to progression and overall survival.

And although our patients achieve the complete response, most of them finally relapsed. And this is one of the main reasons why we needed to improve in the quality of the response and we needed to redefine the complete response definition because according to the IMWG uniform response criteria, we had a complete response, a stringent complete response but both complete response categories include assessment at low sensitivity level and in fact, the stringent complete response category included normal free light chain ratio and absence of clonal plasma cells by immunohistochemistry, so this technique has a very low sensitivity level.

And this is the main reason why we needed to redefine the complete response definition.

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