Thread by @VincentRK

CASSIOPEIA trial maintenance results in myeloma: Main takeaway is that daratumumab maintenance provided ZERO benefit if daratumumab was given as induction/consolidation

This PFS curve (blue versus yellow line) should have been in the main paper, not the Appendix. @TheLancetOncol

Key points

1) When this trial was designed we were already using lenalidomide maintenance as standard. This trial had a no treatment control arm. So the question is how good is Dara maintenance against Len. Not Dara maintenance against nothing.

2) If 6 cycles of Dara given upfront provides the same as many years of Dara maintenance, it is preferable to give the Dara at induction. Not as maintenance.

The myeloma field is moving in this direction giving Dara upfront.

3) If Dara maintenance does not add any benefit if Dara was already used as initial therapy, then it calls into question whether Dara for 4-5 years is needed as part of the DRd regimen studied in the MAIA trial.

Dara maintenance comes with a price: a suppressed immune system.

4) The real questions are to find out who may benefit from Dara maintenance instead of Len maintenance. And who may benefit from Dara plus Len versus Len alone (SWOG trial). Or Len plus PI.

The editorial accompanying this paper by @myelomaMD and @MyelomaDrKapoor goes into these issues that I highlighted. sciencedirect.com/science/articl…

My summary is that for patients getting Dara based induction and transplant, the maintenance therapy recommendation stays the same: Lenalidomide alone for most patients; Lenalidomide plus bortezomib for high risk myeloma.

Enroll on Maintenance trials seeking to improve on this

Trial paper link: sciencedirect.com/science/articl…

For patients getting VRd induction and transplant: Recommendation for maintenance also stays the same. Lenalidomide for standard risk. Lenalidomide plus bortezomib for high risk.

Consider Dara maintenance trials. Consider Dara maintenance if Len not feasible.

For patients on DRd for frontline: Based on CASSIOPEIA maintenance results, the risk of long term immunosupression, & the effect of Dara on antibodies against COVID: Reconsider if Dara needed after 1st year. You can always follow M protein closely.

nature.com/articles/s4157…

Suggestion to authors and companies: Always put the bad news out front and center. Otherwise the only Kaplan Meier figure in the paper (see below) gives a wrong message.

Suggestion to @TheLancetOncol

Can the "Research in Context section" be outside the paywall? At least then a reader knows the meaning of the study. Because reading the abstract alone, the casual reader will miss the main finding. Here is how the abstract presents the findings: