In this analysis of data from the phase 2 FORTE trial, 3 different techniques for characterizing minimal residual disease (MRD), including positron emission tomography/computed tomography (PET/CT), multiparameter flow cytometry (MFC), and next-generation sequencing (NGS), were compared. In the FORTE trial, patients with newly diagnosed transplant-eligible multiple myeloma (NDTEMM) were randomized to arm A (treatment with carfilzomib, lenalidomide, dexamethasone [KRd] induction–autologous stem-cell transplantation [ASCT] intensification–KRd consolidation), arm B (treatment with KRd12), or arm C (treatment with carfilzomib, cyclophosphamide, dexamethasone [KCd] induction–ASCT intensification–KCd consolidation). Following these treatments, they were randomized to lenalidomide alone or lenalidomide plus carfilzomib.
In the FORTE trial, 8-color second-generation flow cytometry was used to evaluate MRD in patients who achieved very good partial response (VGPR) or better before maintenance. In addition, when complete response (CR) was achieved, MRD premaintenance was also assessed using NGS. At defined treatment benchmarks of baseline and preceding maintenance, PET/CT scans were performed and the Deauville scores (DS) were applied both to bone marrow uptake and focal lesions (bone marrow score [BMS]; focal lesion score [FS]).
This analysis included 182 patients (of the 474 enrolled in the study) with matched PET/CT and MFC evaluation. At baseline, focal lesions were present in 92% of patients, with a median maximum standardized uptake value (SUVmax) of 5.7 (interquartile range, 4.1-8.1). Extramedullary lesions were present in 11% of patients, and nearly all patients had increased bone marrow uptake (median SUVmax of 3.5). Focal lesions ≥4 were present in 93% of patients, and bone marrow uptake ≥4 was present in 60% of patients. Preceding maintenance, PET/CT negativity (defined as DS <4) was present in 80% in the focal lesions and 89% in the bone marrow. Neither baseline prognostic factors nor PET/CT characteristics were significantly correlated with PET/CT negativity after therapy. VGPR or better was achieved by 95% of patients, with CR being achieved by 67.5% of patients (MFC MRD negativity in 75%). There was a significant correlation between a best CR and bone marrow uptake <4 at premaintenance (P = .013).
The PET/CT and MFC techniques were strongly concordant in terms of MRD results (Cramér’s V coefficient of 0.76) (P <.001) (n = 133). PET/CT and MFC were concordant in 94% of cases for BMS, whereas PET/CT and MFC were so in 63% of cases for FS. A moderate concordance between PET and NGS (n = 65) was found (Cramér’s V coefficient of 0.39) (P <.038). There was 84% concordance between PET/CT and NGS for BMS and 67% concordance between PET/CT and NGS for FS. There was substantial concordance among the 3 techniques (Krippendorff’s α of 0.60) (P = .001).
This analysis resulted in several important conclusions. First, the applicability and validity of DS criteria for the definition of PET/CT MRD outside the bone marrow were confirmed in an independent group of NDTEMM patients. Second, PET/CT negativity and best CR were significantly correlated. Finally, PET/CT, MFC, and NGS were complementary for focal lesions and showed good concordance in the bone marrow.
Reference
- Abstract and Presentation S207. EHA 2020. June 12, 2020. MRD evaluation by PET/CT according to Deauville criteria combined with bone marrow techniques in newly diagnosed transplant eligible multiple myeloma patients enrolled in the phase II FORTE trial.