Roger Owen St Jamess Institute of Oncology Leeds Minimal Resistant Disease challenges to consider Genomic heterogeneity Spatial heterogeneity Lahuerta et al J Clin Oncol ID: 812728
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Slide1
MRD = Minimal Resistant Disease?
Roger OwenSt James’s Institute of OncologyLeeds
Slide2“Minimal Resistant Disease”: challenges to consider.
Genomic heterogeneity
Spatial heterogeneity
Slide3Lahuerta
et al
, J
Clin
Oncol
2017; 35: 2900-2910
Slide4Rawstron
AC
et al,
Blood
2015, Mar 19; 125(12): 1932–1935
Slide5Rawstron
AC
et al,
Blood
2015, Mar 19; 125(12): 1932–1935
Measurable residual disease
Slide6Perrot
et al;
Blood 2018;132(23):2456-2464.
Slide7Slide8Blood. 2018 Dec 6;132(23):2456-2464
Slide9Phenotype of MRD vs diagnostic plasma cells (n = 40).
Paiva
et al
. Blood 2016;127:1896-1906
Slide10Slide11“Clonal evolution from diagnosis to MRD clonal PCs”
Paiva
et al.
Blood 2016;127:1896-1906
Slide12Impact of MRD at 6M post maintenance randomisation
PFS not reached versus 24 months for MRD-positive patients, HR 0.22
Median PFS
MRD
neg
Not reached
MRD
pos
24m
HR
: 0.22, 95% CI [0.14, 0.34]
Log-Rank P < 0.0001
de
Tute
et al,
ASH 2017
Slide13Benefits of maintenance
PFS advantage demonstrated in both MRD-neg and MRD-pos patients
de
Tute
et al,
ASH 2017
Slide14Benefits of maintenance
Conversions to MRD-negativity were seen in 30% of MRD-positive patients on maintenance compared to 4% of patients randomised to no further therapy (p=0.0045).Conversion noted in all induction therapy groups
Slide15Cohen
et al,
2019
Gambella
et al,
2019
Slide16Benefits of maintenance
Positive to negative conversion is associated with some benefit in PFS
Slide17Slide18Slide19De novo
Relapse / Refractory
MRD-
ve
/ imaging-
ve
30 (36.1%)
8 (24.2%)
MRD-
ve
/
imaging+ve
4 (4.8%)8 (24.2%)
MRD+ve / imaging-ve
39 (47.0%)
10 (30.3%)
MRD+ve
/
imaging+ve
10 (8.4%)
7 (21.2%)
Total
83
33
Slide20Slide21Blood Adv. 2018 Nov 13;2(21):2811-2813
Slide22Conclusions.
Minimal Resistant Disease is complex!Outcomes currently determined by quantitative residual disease and tumour genomicsMRD remains treatment sensitive in some patients MRD plasma cells differ from presentation plasma cells but biological significance remains unclear
MRD markers remains stable
Considerable genomic and spatial heterogeneity which increases with disease progression
Slide23