Topline Presentation Points 

Frontline therapy for transplant eligible multiple myeloma (TEMM)

Anti-CD38 + IMiD + PI + Dex trials: Updates on the “kitchen sink approach” at ASH

ASH Abstract 82. Daratumumab (DARA) with Bortezomib, Thalidomide, and Dexamethasone (VTd) in Transplant-Eligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Analysis of Minimal Residual Disease (MRD) Negativity in Cassiopeia Part 1 and Part 2
Herve Avet Loiseau, MD, PhD, et al.

  • Update of data for sustainability of MRD at 1 and 2 years
    • Dara is important
    • “Maintenance” is important (even in MRD neg CR)
    • Achieving MRD neg CR is important

Additional Presenter Perspective: How to incorporate is not known and long-term follow-up still needed to see if subtle differences in response depth do eventually impact sustainability of MRD, PFS and OS

ASH Abstract 79. Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance
Jacob P. Laubach, et al

  • Update of data examining maximum depth of response over time
    • Dara is important as it markedly increases depth of response
      • Appears to be having an impact on duration of response especially after the 24m mark (importance of achieving MRD negativity before stopping treatment for incurable disease)

Additional Presenter Perspective: Truncated maintenance will not be answered in this study but will be an important comparator to other non-Dara ASCT series and a precursor to larger phase III trials where “indefinite vs finite” maintenance is being examined

Abstract 463. Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone As Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma Patients: The Phase III GMMG-HD7 Trial
Hartmut Goldschmidt, et al.

  • First large phase III Anti-CD38/RVd trial to be presented
  • Examines ability of Isatuximab to improve depth of response pre-ASCT
  • Primary endpoint was MRD negativity after induction
    • Isa is good and boosts RVd induction
    • Improves CR and MRD neg rates

Additional Presenter Perspective: Will need to examine if lesser MRD rates with non-Isa induction can be overcome with Isa in maintenance

Additional Updates with daratumumab combinations

MASTER (Phase II):

  • Dara-KRD with further therapy dictated by MRD status
  • Use of most potent agents to maximize depth of response whereby a MAJORITY of patients achieve MRD negativity
    • Works to possibly even the playing field for those with 1 HR CG feature
    • Response is maintained despite ~80% STOPPING therapy (> 80% relapse free at 24m)
    • Follow-up is very early with respect to durability

Additional Presenter Perspective: Pharmaco-economic analysis of this approach is eagerly awaited (80% of patients will get maximum 1 year of frontline therapy and both K and R will be generic soon with competing anti-CD38 Ab in the current marketplace)

IFM 2018-01

  • Dara-IRD/ASCT/Dara-IRD/R-maint x 26m (Phase II)
    • Standard Risk patients
    • Need to see durability and depth of response
      • Curious it is not as good as GRIFFIN


  • Dara-CRVD/ASCT/DaraRVD/DaraRV/Dara-R maint until progression (phase II)
    • Trial in ultra-high risk MM
    • Provides important comparator to MASTER data in UHiR MM with respect to finite MRD directed therapy vs continuous approach to control suppressed but likely persistent clone.
  • Supports ongoing suppressive therapy for high-risk patients even with high MRD negative CR
  • Encouraging results and likely a niche where the “kitchen sink” is needed

Importance of the immune-microenvironment to predict long-term outcomes

ASH Abstract 329. Normalization of the Immune Microenvironment during Lenalidomide Maintenance Is Associated with Sustained MRD Negativity in Patients with Multiple Myeloma
David G. Coffey, et al.

ASH Abstract 731. Mapping the Multiple Myeloma T Cell Landscape By Immunotherapeutic Perturbation Reveals Mechanism and Determinants of Response to Bispecific T Cell Engagers
Mirco Friedrich et al.

Canadian Myeloma Research Group (CMRG) activity

ASH Abstract 1653. Part 1 Results of a Dose-Finding Study of Belantamab Mafodotin in Combination with Pomalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM)
Suzanne Trudel, et al

  • Evolving option in the post-Lenalidomide and post-daratumumab space for RRMM
  • Belantamab Mafodotin is an immunoconjugate targeting BCMA. Results from earlier phase 1 DREAMM-1 and DREAMM-2 show single-agent activity
  • Belamaf + Pom+ Dex is postulated to enhance immune responses through augmentation of T-cell and natural killer cell–mediated immunity.