September 30th 2021
Optimal Treatment of Relapsed Multiple Myeloma After Standard Induction Failure
Dr. Keith Stewart, Princess Margaret Cancer Centre
Cure is Close, but not there yet!…Until then relapse is common (and drug resistance)
What Is the Future for Relapsed Multiple Myeloma?
- Overview: ~ 20 new therapeutics
- Small Molecules: Iberdomide, Venetoclax, Selinexor, Melfulfen
- Antibodies: Daratumumab, Isatuximab
- Antibody Drug conjugates: Belantamab
- BITES/Bi-specifics: AMG701, Teclistamab, CC93269, REGN4548,Talquetamab, Cevostamab… and many more
- CAR-T: Ide-cel, Ovra-cel, Cilta-cel, LCARB38… many more
Defining & Treating High-Risk Multiple Myeloma
Dr. Saad Usmani, Levine Cancer Institute
- Recognize MM is not one disease. There is a need for small enrichment design clinical trials for high-risk disease.
- Achieving and sustaining MRD negativity matters for HRMM>SDMM
- PI/IMiD based induction/maintenance as options
- Potential strategies to eradicate MRD in TE/TI HRMM:
- CAR-T cell strategies (BCMA, GPRC5D, SLAMF7, FCRH5, etc.)
- Bispecific antibody strategies (BCMA, GPRC5D, FCRH5, etc.)
- Antibody-Drug Conjugates (BCMA, SLAMF7, etc.)
- For Transplant Ineligible elderly MM, use of immune modulation to re-establish immune surveillance and equilibrium.
- Role for immune profiling signatures
- For pPCL: Strategies incorporating BCL2 inhibition being explored
- CelMods, PROTACs, etc.
Cellular Therapy in Multiple Myeloma
Dr. Noopur Raje, Massachusetts General Hospital
Standard Practice in 2021
- Triplets in newly-diagnosed patients: RVD/KRD/VCD
- Daratumumab now approved in first line with VMP Dara-Rd with Rd (MAIA)
- Quadruplets under investigation
- Transplant and maintenance SOC
- Continuous therapy is the accepted treatment paradigm for myeloma
Targeting BCMA as a new standard
- Effective options:
- Antibody drug conjugates – Belantamab mafodotin (August 2020)
- Bispecific T-cell engagers – Several in phase II
- Cellular products – Ide-cel (March 2021)
- Future will be to define how to combine/sequence these
- Next generation approaches will focus on improving efficacy and DOR
- Mechanisms of resistance to anti-BCMA CAR T cell therapy
- Strategies to overcome – dual targeting strategies
- Other MM target antigen candidates for CAR T
- Opportunities for combination treatment
Older Patients with Classical Hodgkin Lymphoma
Dr. John Kuruvilla, Princess Margaret Cancer Centre
- Outcomes are inferior in older patients
- Age 60 may not be a relevant cutoff in clinical practice, 70 appears more relevant
- Cause of death is not driven by lymphoma deaths, but disease control is also a problem
- Patients are under-represented in clinical trials
- Second-line outcomes are also inferior
- Biology not clearly understood, biomarkers absent
- Outcomes with novel agents are also suboptimal
- But goal in this population is to improve disease control and to improve acute and late toxicity
- Optimal Approaches for Primary Therapy of elderly cHL
- Optimal Approaches for RR-cHL in elderly
- No clear Standard of Care in RR-cHL patients ineligible for ASCT
- Salvage therapy Outcomes in the Elderly
Integrating Novel therapy in Second-Line Hodgkin Lymphoma
Dr. Alison Moskowitz, Memorial Sloan Kettering Cancer Center
Best second-line therapy?
- Chosen according to baseline risk factors
- Prior therapy
- Baseline metabolic tumor volume (MTV)
- Geared toward markers of treatment sensitivity
- 9p24.1 amplification
- Modified according to early markers
- Interim PET
- Reduction in MTV or ctDNA
Early Stage classical Hodgkin Lymphoma
Dr. Graham Collins, Oxford Cancer and Haematology Centre
- Overview of the prior standard based on GHSG trials
- Overview of response adaptation trial data:
- UK RAPID study
- EORTC H10 study
- New kid on the block: HD17
- Individualizing the radiotherapy late effects risks
- Future directions
Radiation Therapy in the Upfront Management of Hodgkin Lymphoma
Dr. David Hodgson, Princess Margaret Cancer Centre
- There is no “one size fits all”.
- ABVD x 6 for everyone or CMT in every early-stage case not best practice.
- Getting to the right decision requires multi-disciplinary input and is often a value judgement and therefore requires patient input and physician patience.
- Aim to keep breast mean dose <4Gy and cardiac mean dose <10Gy and limit doxorubicin exposure.
- Brentuximab, Nivolumab in upfront management to replace doxorubicin & RT for selected patients.
- Better risk stratification – [as available] use quantitative PET metrics, biomarkers.