Background: Evaluation of minimal residual disease (MRD) in multiple myeloma (MM) has become a standard procedure and has been incorporated to International Myeloma Working Group updated response criteria in 2016. Its value as an important prognostic factor with impact on survival as well as a relevant end-point in clinical trials has been established by many studies. Assessment of MRD inside the bone marrow is performed basically by two standardized techniques: i) next generation flow cytometry (NGF) and ii) next generation sequencing (NGS). Positron emission tomography and computed tomography (PET/CT) is currently considered as a best tool to evaluate MRD outside of the bone marrow. The standard timepoint to assess the MRD by PET/CT in transplant eligible newly diagnosed multiple myeloma (TE NDMM) patients is considered Day +100 post-autologous stem cell transplantation (ASCT) according to largest CASSIOPET study (Moreau et al., Blood, 2019). Nevertheless, this kind of data from real-world outside the clinical trials setting remains limited.
Aim: To evaluate the prognostic impact of PET/CT performed on Day +100 post-ASCT in consecutive cohort of real-world TE NDMM patients from a single center in the Czech Republic.
Methods: 18 TE NDMM patients with median age of 59 years (range 42 - 71 years), ISS stage III 17% (3/18) diagnosed between September 2017 and June 2019 received proteasome inhibitor plus immunomodulatory drug containing induction. Patients who reached at least very good partial response (VGPR) after ASCT were indicated for MRD evaluation using NGF technique according to standardized EuroFlow protocol with sensitivity to 10e-6 and for PET/CT evaluation - both at Day +100 post-ASCT. For the evaluation of PET/CT scans complex evaluation by nuclear medicine specialist based on Italian Myeloma criteria for PET Use (IMPeTUs) criteria were used (IMPeTUs) criteria were used (Nanni et al., Eur. J. Nucl. Med. Mol. Imaging. 2018).
Results: Of 18 evaluated TE NDMM patients (17 in complete remission (CR), 1 in VGPR), there were 78% (14/18) considered PET/CT negative and 22% (4/18) were considered PET/CT positive at Day +100 post-ASCT. Patients who were PET/CT positive had significantly shorter median PFS (mPFS 29 days) versus those who were PET/CT negative (mPFS not reached); p value < 0.001. Calculated median follow-up for the whole cohort was 245 days. Interestingly, one patient who was NGF MRD negative within the bone marrow was considered PET/CT positive and has early relapse after ASCT.
Conclusion: We demonstrated on limited number of real-world TE NDMM patients that those who are PET/CT positive at Day +100 post-ASCT have significantly shorter mPFS compared to those who are PET/CT negative. The aim of myeloma community should lead to the implementation of simultaneous assessment of MRD inside the bone marrow in combination with imaging technique (PET/CT) outside the bone marrow, as this combined evaluation seems to be the most important prognostic factor. Moreover, great effort should be make to establish standardized evaluation protocols for nuclear medicine specialists as well as the most appropriate time-points to perform PET/CT, such as Day +100 post-ASCT in TE NDMM.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.