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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- Our experience and strategies
- Why is MRD testing relevant in multiple myeloma?
- Selected treatment responses in newly diagnosed MM patients
- Proportion of MRD-negative patients (10–4, 10–5, and 10–6) on POLLUX study
- BCMA CAR T-cell therapy and MRD negativity in relapsed/refractory patients
- Why is MRD testing relevant in MM?
- MRD negativity associated with 50% reduced risk of progression (HR~0.5)
- The focus of my talk
- Hypothesis: can MRD guide therapy in newly diagnosed patients?
- Current treatment paradigm for newly diagnosed MM
- Hypothesis: MRD-guided use of transplant in newly diagnosed patients
- Support from the literature
- Determination trial (IFM 2009): newly diagnosed MM
- IFM 2009 follow-up study: focus on MRD
- IFM 2009 follow-up: final MRD results
- MSKCC treatment paradigm
- MRD-driven treatment for newly diagnosed myeloma patients
- MRD negativity, longitudinal testing
- Quantitative multiplex imaging of bone marrow microenvironment
- Single cell RNA sequencing ongoing: developing DNA-based assays
- High-dimensional screening of soluble immuno-oncology proteins in serum
- Hypothesis: should relapse treatment be started at MRD+?
- Recurrent MM in my clinic
- Monitoring on maintenance in my clinic
- Current thinking
- Updated response criteria focus on MRD, but relapse definition is still old…
- Treatment paradigm for progressive disease in MM is old, too…
- Future directions
- Conversion of MRD and clinical relapse
- Wait = waiting for the disease to further evolve genomically
- Hypothesis: starting therapy in multiple myeloma patients who become MRD+
- Short course (6 months) daratumumab and Revlimid to revert MRD+ to MRD-
- Where is the myeloma field going? (1)
- Where is the myeloma field going? (2)
- Selected 4-drug combinations being studied in newly diagnosed myeloma
- Bone marrow biopsy (H&E) at diagnosis
- Bone marrow biopsy (CD138) at diagnosis
- Bone marrow biopsy (CD138) after 1 cycle daratumumab-KRd
- MRD testing in myeloma included in the IMWG 2016 guidelines
- MRD testing in myeloma: circulating tumor DNA in peripheral blood (1)
- MRD testing in myeloma: circulating tumor DNA in peripheral blood (2)
- MRD testing in myeloma: immuno-PET
- MRD testing in myeloma: immuno-PET in mice
- Immuno-PET in mice
- MRD testing in myeloma: immuno-PET in human
- Immuno-PET in human (1)
- Immuno-PET in human (2)
- Summary and conclusions
- Evolution and future directions for therapy and MRD testing in MM patients
- What are the clinical needs?
- MSK Myeloma Program & collaborators
- Thank you for your attention!
Topics Covered
- MRD testing in Multiple Myeloma (MM)
- Selected treatment responses in newly diagnosed patients
- MRD negativity and disease progression
- Determination trial (IFM 2009)
- MSKCC treatment paradigm
- Developing DNA based assays
- Recurrent MM
- MRD positivity
- Different drug combinations
- MRD testing
- Future directions
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Landgren, O. (2020, July 30). MRD-driven multiple myeloma treatment: next step forward [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 7, 2024, from https://doi.org/10.69645/YTKO5525.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Landgren has received research funding from: National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), Multiple Myeloma Research Foundation (MMRF), International Myeloma Foundation (IMF), Leukemia and Lymphoma Society (LLS), Perelman Family Foundation, Rising Tides Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; Honoraria/ad boards: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and serves on Independent Data Monitoring Committees (IDMCs) for clinical trials lead by Takeda, Merck, Janssen.
Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms
Transcript
Please wait while the transcript is being prepared...
0:00
Hi, I'm Ola Landgren.
I'm Chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center and
Professor of Medicine at Weill Cornell Medical College in New York City.
Today I will give a talk about MRD Driven Multiple Myeloma Treatment: Next Step Forward.
0:18
These are my disclosures.
0:23
I also would like to emphasize that a lot of the slides I will share
with you today cover our experience and our strategies,
and I'm well aware that there are
other perspectives and I'm of course very respectful of those.
0:35
Let's start with the question,
why is MRD testing relevant in multiple myeloma?
I think there are two major aspects to address here.
Number 1, MRD negativity can be achieved in both
newly diagnosed and relapsed or refractory patients with multiple myeloma.
So it's in every stage of the disease.
Also, number 2, MRD status is not only something you can find,
it's also a strong predictor of clinical outcomes in multiple myeloma.
I will share with you a couple of slides to illustrate a little
bit further what I mean when I show these two bullets.
1:12
Number 1, here we have selected
treatment responses in newly diagnosed patients with myeloma,
and I selected on the very left,
one old study back from 2003 in the New England Journal of Medicine,
using the old VAD regiment with one versus two transplants,
then if you move to the right,
you have the VRd or RVd regiment plus-minus transplant,
this is the 2009 IFM study.
Then you move to the right,
you have the single-arm KRd without transplant.
There's not yet any published study with comparison between KRd and other regiments.
So for now, this is the only published paper with a single arm.
Then we have the VMP plus-minus daratumumab,
then we have on the very right,
Rev/Dex plus-minus velcade also without transplant.
As you see here, the three middle studies,
they all include MRD testing.
The left and the right study,
they do not include that.
If you look in further detail in the middle,
you see that MRD status as expected ranges quite a lot, for example,
the transplant arm on the VAD plus-minus transplant on the left goes as high
as 79 percent and the RVd arm is 65 percent.
If you move to the very right, again,
you see that the Dara-VMP arm is 22 and the VMP arm is only six percent.
There is some evidence of MRD negativity even in VMP.
Then in the middle, you see 77 and 42 percent.
If you look even closer,
you see that the level of MRD negativity is different in these different studies.
The study on the left reports 10 to minus four,
which formally is really not MRD negativity.
The definition by current criteria is 10 to minus five.
They are saying here that one cell in 10,000 has been
ruled out and then they declare that's true in 79 percent.
But it should really be one cell in 100,000
if you follow guidelines, 10 to minus five.
There is also emerging data that if you raise the bar 10 to minus six,
so that's one cell in a million,
that that could even be a stronger predictor for better progression-free survival.
So I caution you when you look across these different studies.