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Immunotherapy for Multiple Myeloma. Hearn Jay Cho MD, PhD Mt. Sinai School of Medicine. Disclosures. Clinical research support Ludwig Institute for Cancer Research Laboratory research support Cancer Research Institute NIH/NCI

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immunotherapy for multiple myeloma

Immunotherapy for Multiple Myeloma

Hearn Jay Cho MD, PhD

Mt. Sinai School of Medicine

disclosures
Disclosures
  • Clinical research support
    • Ludwig Institute for Cancer Research
  • Laboratory research support
    • Cancer Research Institute
    • NIH/NCI
  • I will discuss investigational applications of FDA-approved and investigational agents
rationale for immunotherapy
Rationale for Immunotherapy
  • Durable complete remissions reported for allogeneic stem cell transplantation
    • Immunologic therapy, “graft-versus-tumor effect”
  • Donor lymphocyte infusion rescues patients who relapse after allo-transplant
    • T cell-mediated anti-tumor immunity
  • Humoral and cellular immune responses against myeloma-associated antigens detected in patients
    • Pre- and post-treatment, allo transplant
immunotherapeutic strategies
Immunotherapeutic Strategies
  • “Targeting” monoclonal antibodies (mAbs)
  • Immune checkpoint inhibitors
  • Adoptive cell therapies
    • Transgenic T cell receptor (TCR)
    • Chimeric antigen receptors (CAR)
  • Therapeutic tumor vaccines
targeting mabs
“Targeting” mAbs

* Immunotoxin conjugate

targeting mabs2
Targeting mAbs
  • Elotuzumab
    • Elo Len Dex Ph 2 relapse, PFS 33 months, ASCO 2013
    • FDA Breakthrough Therapy 2014
  • Daratumumab
    • Dara ± Len Dex Ph1/2 relapse, high response rate, ASH 2013
    • FDA Breakthrough Therapy/ Fast Track 2014
targeting mabs mechanisms
Targeting mAbs Mechanisms
  • Elotuzumab
    • Activates NK cells, renders them capable of killing SLAMF7(-) tumor cells. Cancer ImmunolImmunother 62:1831
  • Daratumumab
    • CD38 ectoenzyme catalyzes critical step in NADAdenosine metabolism, modulates TCR signaling. J Mol Med 91:165
immune checkpoint inhibitors
Immune Checkpoint Inhibitors

* FDA approved

** Breakthrough Therapy

checkpoint inhibitors trials
Checkpoint Inhibitors Trials
  • Basket trials
    • Ipilimumab + Nivolumabheme malignancy
    • MPDL3280A in solid tumors and heme malignancy
  • Combination
    • Pembrolizumab + len/dex
    • Pidilizumab + DC fusion vaccine
  • Post-allo-SCT
    • Ipilimumab
vaccine immunotherapy
Vaccine Immunotherapy
  • Cell-based vaccines
    • Dendritic cell vaccines
    • Tumor cell vaccines
      • Autologous or cell lines
  • MHC-restricted peptide vaccines
  • “Universal” vaccines
    • Recombinant proteins
    • Synthetic long peptides
    • Plasmid DNA vaccines
myeloma associated antigens
Myeloma-associated Antigens
  • Idiotype
    • Myeloma-specific
    • Poor results in clinical trials
  • Tumor-associated Antigens
    • WT1
    • Muc1
    • hTERT
  • Cancer-Testis Antigens
    • Expressed in many cancers
    • Restricted expression in normal tissue
    • Type I MAGE (MAGE-A3 and CT7), NY-ESO-1, SSX2 expressed in myeloma
slide14

LGS2009-005: Summary (overlay) by clinical site for MAGEA3 O/L Peptides

Event

1

Event

2 4

Event

8 9 10

Event

11 12

Event

13 14

Event

15 16

Event

18

days

days

Days from auto-stem cell transplant

d0 auto-SCT + d3 PBL reinfusion

Cohen et al, ASH 2013

future directions
Future Directions
  • Combination immuno- and targeted therapy
    • Cytotoxic + immuno/ Auto-SCT + immuno
    • ImiDs + immunotherapy
    • Polyvalent vaccines
  • Consolidation for non-auto-SCT candidates
  • MGUS/ smoldering MM