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NI I HO T T OP I C Questions raised around MYELOMA TREATMENTS Fredrik Schjesvold In Sweden, a recent debate and criticism regarding approved multiple myeloma treatments has shone the spotlight on IMiDs and their effects. NLS asked Fredrik Schjesvold, MD, PhD, founder and leader of Oslo Myeloma Center, Oslo University Hospital, about these drugs and the ongoing debate. 14 | NORDICLIFESCIENCE.ORG N AN OP-ED in Läkartidningen (October 3, 2024), Jakob Lindberg, former CSO and CEO of Oncopeptides and currently an advisor in research matters, and Per Sjöberg, consultant and former Head of the Swedish Medicines Agency's pharmacological and toxicological unit, draw attention to two, according to them, serious problems of immunomodulatory drugs (IMiDs) and how they are prescribed to multiple myeloma (myeloma) patients. Background Lindberg and Sjöberg refer to data published in August 2024, showing that the effect of IMiDs on observed survival in myeloma patients decreases significantly with increased patient age without changing biomarker data (progression-free survival, PFS) (Pawlyn et al, Blood Cancer J. 2024). The study states that surrogate endpoints of overall survival (OS), such as PFS and response to treatment, have contributed to approval decisions by the FDA and the EMA as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in myeloma. The review address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The use of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed in the article. According to Lindberg and Sjöberg, the first serious problem is the public information regarding the three registration studies MM009, MM010 (lenalidomide) and MM003 (pomalidomide). They state that it gives a false positive picture of the survival effects of lenalidomide and pomalidomide without addressing the high-dose dexamethasone problem (the observed survival results are the basis for the role of IMiDs in treatment guidelines). The second problem they point out is the large amount