MRD Status Comparison by 3 Techniques in Patients with Newly Diagnosed Transplant-Eligible MM

According to data from the phase 2 FORTE trial, 3 different techniques were analyzed and compared to characterize minimal residual disease (MRD), including positron emission tomography/computed tomography (PET/CT), multiparameter flow cytometry (MFC), and next-generation sequencing (NGS).

Patients with newly diagnosed transplant-eligible multiple myeloma (MM) who were enrolled in the FORTE trial 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). After these treatments, patients were randomized to treatment with lenalidomide alone or lenalidomide plus carfilzomib.

In patients who achieved very good partial response or better (≥VGPR) before maintenance, 8-color second-generation flow cytometry was used to evaluate MRD in the FORTE trial. In addition, MRD premaintenance was also assessed using NGS when complete response (CR) was achieved. 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).

A total of 182 patients (of the 474 enrolled in the study) with matched PET/CT and MFC evaluation were included in this analysis. At baseline, focal lesions were present in 92% of patients; median maximum standardized uptake value (SUVmax) was 5.7 (interquartile range, 4.1-8.1). In 11% of patients, extramedullary lesions were present and nearly all patients had increased bone marrow uptake (median SUVmax, 3.5). In 93% of patients, focal lesions ≥4 were present, and in 60% of patients, bone marrow uptake ≥4 was present. Preceding maintenance, PET/CT negativity (defined as DS <4) was present in 80% and 89% in the focal lesions and bone marrow, respectively. After therapy, neither baseline prognostic factors nor PET/CT characteristics were significantly correlated with PET/CT negativity. A total of 95% of patients achieved ≥VGPR; CR was achieved by 67.5% of patients (MFC MRD negativity in 75%). A significant correlation was found between a best CR and bone marrow uptake <4 at premaintenance (P = .013).

In terms of MRD results, the PET/CT and MFC techniques were strongly concordant (Cramér’s V coefficient, 0.76; P <.001; N = 133). In 94% of cases for BMS, PET/CT and MFC were concordant, whereas in 63% of cases for focal lesion score, PET/CT and MFC were concordant. A moderate concordance between PET and NGS (N = 65) was found (Cramér’s V coefficient, 0.39; P <.038). Concordance rates were 84% between PET/CT and NGS for BMS and 67% between PET/CT and NGS for focal lesion score. Substantial concordance was found among the 3 techniques (Krippendorff’s α, 0.60; P = .001).

Several important conclusions came from this analysis. First, in an independent group of patients with newly diagnosed transplant-eligible MM, the applicability and validity of DS criteria for the definition of PET/CT MRD outside the bone marrow were confirmed. Second, best CR and PET/CT negativity were significantly correlated. Third and finally, for focal lesions, PET/CT, MFC, and NGS were complementary 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.

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