MGUS and SMM (0:15-3:17)
- iStopMM study Iceland (ASH 2021)
- Prevalence of SMM
- Impact of screening, work-up, follow-up
Risk stratification in MM (3:17-5:28)
- Chromosome 1 abnormalities important. (ECOG study E1A11, Schmidt, TM et al. ASH 2021)
- Gain1q, amp1q, and del1p confer inferior PFS among pts with otherwise standard risk features who are treated with VRd or KRd induction
- In multivariate analysis, +1q was an independent prognostic factor for poor PFS
- There were no significant differences in PFS among patients with +1q or del1p based on receipt of VEd or KRd
- Possible OS benefit for KRd among patients with gain1q, del1p and “ultra high risk”.
- Classification warrants further review
Newly Diagnosed MM (NDMM) (5:29-10:59)
- GRIFFIN – Phase 2 study of D-RVd vs RVd in transplant eligible NDMM (Anderson et al, Blood 2021)
- Response rates for sCR and > CR were greater for D-RVd vs RVd at all points, with the deepest responses occurring after 2 years of maintenance therapy
- Anticipate Canadian clinicians will add Daratumumab to induction
- MRD- negativity rates improved throughout DR maintenance period
- PFS in the ITT Population
- GMMG-HD7 Phase III Trial – Isatuximab VRD (Goldschmidt et al. ASH 2021)
- First primary end point, end of induction
- MRD negativity by NGF 10⁻⁵, was met in ITT analysis
- Isa-RVd is the first regimen to demonstrate a rapid and statistically significant benefit from treatment by reaching a MRD negativity of 50.1% at the end of induction and to show superiority vs RVd in a Phase 3 trial
- MASTER Trial – Dara-KRd (Costa, LJ et al. ASH 2021)
- Very powerful and effective regimen
- Not as effective in ultra high risk
- Not available in Canada
Relapsed MM (11:01-23:40)
Treatment for Myeloma is being further disrupted with a number of new agents that show significant activity in heavily pre-treated
CAR T
CARTITUDE-1b/2 – Cilta-cel (Martin et al. ASH 2021)
- Remarkable efficacy with 98% response rate
- 2 year PFS 71% for sCR patients and 60.5% all patients
- 2 year OS 74%, significant for patients who would normally not expect a year
Other CAR-T targeting BCMA -liso-cel 90% response
Bi-specific antibodies (BiTEs) targeting BCM
Teclistamab (most advanced)
- MajesTEC-1 trial in highly refractory patients
- 62% ORR, response rapid and MRD negativity of 24.7% at threshold of 10⁻⁵
- Well tolerated
Tnb383B
- Higher ORR at 82% with serious AEs occurring in 46% patients
Other – Regn5468, Elranatamab, CC93269, AMG701
‘Off the shelf’ T-Cell engagers
GP3C5D-targeted CAR T
- Talquetamab a promising target MonumenTAL-1 trial 70% ORR
FcRH5 and CD3
- Cevostamab a dual targeted BiTE
Other agents
Ven+Bort+Dex (Phase 3 BELLINI trial)
- PFS was significantly prolonged in Ven+Bd vs Pbo+Bd
- Greatest PFS improvements observed in patients with t(11;14) or BCL2ʰᶦᵍʰ expression
- Patients with these translocations 11 and 14 can do well on Ven
Iberdomide – a potent novel CELMoD agent, being developed as a next generation IMiD for rrMM
(Phase 1/2b CC-220-MM-001)
Amyloidosis (23:40-24:38)
ANDROMEDA study update of D-VCd vs VCd
- At a medium follow-up of 25.8 months, hematological response rates remained higher with D-VCd vs VCd
- Organ response rates at 18 months remained higher with D-VCd vs VCd
