General MM

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

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 Haematologica in 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 vs patients 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.

References
  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