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Prognostic significance of myeloma PET-CT focal lesions
between patients with suppression of baseline FL by day 7 compared to patients with at least one FL at day 7 (Online Supplementary Table S1 and Online Supplementary Figures S4 and S5). Multivariate analysis and R2 values sug- gest that both GEP and persistent FL positivity contribute to clinical outcome both at presentation and at subsequent time points, with presence of FLs making a very signifi- cant contribution to outcome (Table 5).
Relationship between imaging response and minimal residual disease
To address how imaging response relates to BM MRD, we looked at cases who had achieved a standard CR (as defined by the IMWG criteria) and had MRD assessment at the level of 1 in 104 performed by flow cytometry analy- sis. We identified 13 cases with 1 or more FLs at the time
of MRD assessment; of these, 8 were MRD positive and 5 were MRD negative. This distribution of MRD was not significantly different from the distribution in cases with 0 FL (55 positive and 37 negative) (Fisher’s exact test P=0.90). This observation highlights the importance of combining imaging with MRD assessment.
Discussion
We demonstrate in a large statistically robust data set that the serial use of PET-CT assessment can contribute to risk assessment and the prediction of outcome. We show that 62% of patients have PET-CT detectable FLs at diag- nosis with a greater percentage in HR compared to LR patients. We show that, following modern day therapy,
Table 3. Progression-free and overall survival estimates at each positron emission tomography with computed tomography time point according to the number of focal lesions.
Presentation
N. of focal lesions
0 1-3 >3
3-year estimated progression-free survival % (95% CI)
74 (68, 80) 74 (67, 81) 59 (52, 65) 76(67,86) 72 (63, 81) 53 (45, 60) 72 (64, 80) 73 (67, 79) 54 (44, 64) 74 (65, 84) 72 (65, 79) 57 (40, 74) 76 (65, 86) 66 (58, 74) 52 (28, 76)
3-year estimated overall survival % (95% CI)
89 (84, 93) 85 (79, 91) 72 (66, 78) 89(82,96) 86 (80, 93) 72 (64, 78) 88 (82, 94) 82 (76, 87) 71 (63, 80) 87 (80, 94) 80 (73, 86) 76 (61, 90) 88 (79, 96) 80 (73, 86) 60 (37, 83)
Day7 0
End of induction
Post transplant
Maintenance
N.: number; CI: Confidence Interval.
1-3 >3 0 1-3 >3 0 1-3 >3 0 1-3 >3
Table 4. P-value for progression-free and overall survival estimates for patients with and without lesions at each positron emission tomography with computed tomography time point.
Progression-free survival Overall survival
PP
>0FLatday7
vs. no lesions at baseline
vs. lesion(s) at baseline, resolved by day 7 >0 FL at post induction
vs. no lesions at baseline
vs. lesion(s) at baseline, resolved by day 7 >0 FL at post transplant
vs. no lesions at baseline
vs. lesion(s) at baseline, resolved by day 7 >0 FL at maintenance
vs. no lesions at baseline
vs. lesion(s) at baseline, resolved by day 7 FL: focal lesion; P: P-value; NS: not significant.
0.0002 0.0001
0.0001 0.0015
0.0069 NS 0.0064 NS
0.0035 NS 0.0070 NS
NS
NS
0.0020
0.0187
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