Pre-maintenance positron emission tomography/computed tomography and bone marrow multiparameter flow cytometry are important for prognostication in multiple myeloma treated with daratumumab

1. Pre-maintenance positron emission tomography (PET)/computed tomography (CT) and bone marrow multiparameter flow cytometry (BM MFC) are associated with better progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab.

Evidence Rating Level: 1 (Excellent)

Previous studies have shown that BM MFC and PET/CT double negativity in patients with multiple myeloma achieved prolonged PFS compared to patients who were not double negative. However, these findings predate the current era of anti-CD38 monoclonal antibodies, which are currently the standard of care. CASSIOPET is the companion study of CASSIOPEIA, where patients with NDMM were randomized to receive daratumumab, a CD38-targeting monoclonal antibody, plus bortezomib/thalidomide/dexamethasone (D-VTd) or bortezomib/thalidomide/dexamethasone (VTd). These patients then received autologous stem cell transplant (ASCT), and those who achieved a partial response underwent observation-only or maintenance therapy with daratumumab monotherapy. CASSIOPEIA patients were eligible for inclusion in CASSIOPET if they had undergone a PET/CT scan within 6 weeks before the first randomization. 225 patients (median [IQR] age, 59 [8] years; 56.4% male) were included. PET negative patients had better PFS (HR, 0.48; 95% confidence interval [CI], 0.25-0.90; P = .019) and a major trend toward better overall survival (HR, 0.37; 95% CI, 0.12-1.07; P = .056). Patients who achieved both PET and MFC negativity had better PFS than those with at least one positive result (HR, 0.39; 95% CI, 0.26-0.60; P < .0001). These studies confirm the prognostic relevance of pre-maintenance PET and BM MFC in NDMM patients treated with daratumumab. Double negativity may be a criterion to guide maintenance intensity in NDMM.

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