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Treatment to suppression of focal lesions in NDMM is an important therapeutic goal

Apr 16, 2018

Clinical imaging is increasingly used for both diagnosis and therapeutic assessment of numerous cancers. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) with computed tomography (CT) attenuation correction (18F-FDG PET/CT) evaluates glucose metabolism, providing a quantitative readout for the presence of active lesions.

Faith E. Davies, from the Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, US, and colleagues, conducted a study in which they analyzed the prognostic significance of suppressing PET/CT activity in focal lesions (FLs)  of newly diagnosed multiple myeloma (NDMM) patients, at various time points after therapeutic intervention. The study was published in Haematologicain March 2018.

Study design:

  • PET-CT analysis data were collected from 596 patients (pts) enrolled in the TT4-TT6 clinical trial series
  • Treatment included combination chemotherapy as induction with double autologous stem cell transplant (ASCT), post-transplant consolidation, and 3-years of planned maintenance with lenalidomide, bortezomib, and dexamethasone
  • PET-CT scan protocol:
    • IV administration of 10-15 mCi (370-555 Mbq) of FDG following 6-8 hrs of fasting
    • Images were acquired 50-70 min after injection
    • FLs defined as areas measuring at least 1cm
  • Clinical response was assessed using International Myeloma Working Group (IMWG) definitions and flow cytometry was used to assess minimal residual disease (MRD)

Patient characteristics:

  • Age ≥ 65 years = 33%
  • Cytogenetic abnormalities = 44%
  • International staging system (ISS) Stage 1 = 33%; Stage 2 = 42%; Stage 3 = 26%
  • GEP70 classification:
    • Low risk patients (pts) = 467; High risk pts = 71
  • Three-year survival estimates:
    • Progression-free survival (PFS) = 68% (95%, CI; 65–72)
    • Overall survival (OS) = 82% (95%, CI; 78–85)
  • Median follow-up = 5.1 years

Key Findings:

  • Association between the presence of ≥ 3 FLs (identified using PET-CT) at baseline and adverse PFS ( P< 0.0001) and OS ( P< 0.0001)
Table 1. Clinical outcome estimates at each PET-CT timepoint in relation to the number of focal lesions

  • No significant difference in PFS and OS between patients who achieved 100% suppression of FL post-therapy at each time-point studied (day 7, end of induction, post-transplantation, and maintenance) and patients with no FL present at baseline
  • A significantly better outcome in patients with undetectable FLs at each time-point in comparison to patients with ≥ 1 detectable FL
  • There was an association between a sustained signal at the FL and adverse outcomes
  • Significant association between GEP70 low risk (LR) pts with ≥ 3FLs and an adverse outcome (PFS: P= 0.007; OS: P< 0.001)
  • Association between GEP70 high risk (LR) pts with FLs and an adverse outcome (PFS: P= 0.04; OS: P= 0.05)
  • Significant difference between patients with no FL at baseline and day 7 vspatients with ≥ 1 FL at day 7, in terms of OS (for GEP70 low risk pts, P= 0.0025; for GEP70 high risk pts, P= 0.0211) and PFS (for GEP70 low risk pts, P= 0.0085; for GEP70 high risk pts, P= 0.0009)
  • Strong association between GEP70 high-risk status, sustained FL positivity and clinical outcome at all time points studied
  • PET/CT imaging detected FLs when MRD was negative using flow cytometry

This analysis demonstrates the valuable contribution of PET-CT imaging to the prediction of clinical outcome. NDMM patients who displayed no PET-CT FL activity after treatment by day 7, or by the end of induction, displayed a similar clinical outcome to patients who presented with no FLs at the time of diagnosis. Additionally, the results demonstrate a strong association between NDMM patients with 3 or more focal lesions and a poor PFS and OS. The authors of this study propose the integration of serial PET-CT as part of a strategic treatment plan.

  1. Davies FE. et al.Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma. Haematologica.March 2018. DOI: 10.3324/haematol.2017.177139