Myeloma

 1. Frontline transplant eligible: VRD dara for younger patients stringent CR, depth of response and MRD all higher with quadruplet. Translates to better PFS. Trend toward better OS.

CASSIOPEIA ( VTD-dara) and GRIFFIN ( VRD-Dara).

2. Relapsed MM:  First relapse: ( second line)

Bortezomib is suboptimal at the time of the first relapse for len-refractory patients based on CASTOR study results

Len refractory ( progression on len or within 60 days of last dose): Dara or Isatuximab ( anti CD 38 antibody) with second gen PI ( Karfilzomib) with low dose dex

a. Dara- Kd--> CANDOR --> PFS 29 months ( for all comers, 1/3 len refractory)

b. Isa-Kd--> IKEMA--> PFS 36 months ( all comers, 1/3 len refractory). Kd arm PFS 15 m

Lenalidomide sensitive patients at the time of first relapse: POLLUX study-- Dara - len-dex-- median PFS 4 yr.

3. Relapsed myeloma: second relapse: ( third line)

 Pom/dex backbone with CD 38 antibody: ICARIA and APOLLO

a.  Istatuximab + Len/dex: ICARIA:  PFS, 11.5 months, versus 6.5, with a hazard ratio of 0.6. So that’s a 40% reduction in the risk of death of progression with isatuximab/pom/dex versus pom/dex alone

b. Dara-Pom dex- APOLLO: Median PFS 12 months for triplet versus 7 for Pd alone. Of note Dara was used subcut not IV.

4.  What is Iberdomide? It is a CELMoD. Cerebron ligase modulators have more affinity in binding and degrading substrates needed by the myeloma cell. 10-20 times more potent than Lenalidomide.

5. If you progress on an anti CD 38, how long should the patient be off the antibody before you retreat? Ans: at least 6 months for the CD 38 to get expressed again on the myeloma cells.

6. MAIA study elderly non transplant eligible: the median progression-free survival was 44.5 months in the daratumumab group, as compared with 17.5 months in the control group.