Topline Presentation Points
Acquired Resistance
- Proteasome Inhibitors – Proteasome Subunit mutation, XBP-1 mutation
- All IMiDs and CelMods – CRBN pathway
- Daratumumab – Loss of CD38
- CAR-T/TCE – Loss of BCMA
Gene Expression levels of Cereblon, Mutations in the Cereblon pathway and CRBN pathway change
A majority of MM patients now receive bortezomib and lenalidomide in first line therapy and maintenance
- Ideal therapy at time of first progression would be non cross reactive, with novel MOA, well tolerated and effective
- Pomalidomide – same MOA, low toxicity
- Carfilzomib – same MOA, superior to Bortezomib in relapse
- Cyclophosphamide – same MOA (unless not transplanted), good partner, not as effective
- Daratumumab and Isatuximab novel MOA, low toxicity
Lots of options in drug sensitive early relapse
What to do in the inevitable lenalidomide and / or daratumumab refractory patients ?
- Pom Dex PFS in Len refractory 7 months
(Dimopoulos MA, et al. ASH 2020. Abstract 412.)
- Carfilzomib/Dexamethasone 19 months
(Dimopoulos MA et al. Lancet Oncol. 2016;17:27-38.)
- KCd: 21 months
(Mateos MV, et al. Blood. 2020;136(suppl 1):8-9.)
