2021
DOI: 10.1001/jamaoncol.2021.0611
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Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma

Abstract: IMPORTANCERecently, the benefit of adding daratumumab to the proteasome inhibitor-based, 3-drug combination of bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed multiple myeloma who underwent high-dose melphalan chemotherapy and autologous hemopoietic cell transplant was assessed. Here, we examine the addition of daratumumab to the second-generation proteasome inhibitor-based, 3-drug combination of carfilzomib, lenalidomide, and dexamethasone. OBJECTIVE To assess the safety and effe… Show more

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Cited by 82 publications
(56 citation statements)
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“…Contrarily, we now demonstrate that decreased poly-IgG levels and high-risk cytogenetics (potentially, being a surrogate for higher employment of PI), were both associated with higher risk of infections. In line with other studies, 2 9 , 12 the infections sustained in our cohort were mainly respiratory and observed mostly among the Dara + -VRD-treated patients. Nevertheless, most infections were only grade 1–2, as reported by others, 2 , 3 , 6 8 , 12 suggesting that infections, though frequent, are unlikely to be life-threatening and are often self-resolving.…”
Section: Discussionsupporting
confidence: 92%
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“…Contrarily, we now demonstrate that decreased poly-IgG levels and high-risk cytogenetics (potentially, being a surrogate for higher employment of PI), were both associated with higher risk of infections. In line with other studies, 2 9 , 12 the infections sustained in our cohort were mainly respiratory and observed mostly among the Dara + -VRD-treated patients. Nevertheless, most infections were only grade 1–2, as reported by others, 2 , 3 , 6 8 , 12 suggesting that infections, though frequent, are unlikely to be life-threatening and are often self-resolving.…”
Section: Discussionsupporting
confidence: 92%
“… 19 , 20 As mentioned earlier, treatment type has also an impact on immune function; for example, PIs depletes alloreactive T cells and dexamethasone also suppresses cell-mediated immunity, 21 , 22 whereas monoclonal antibodies induce a significant hypogammaglobulinemia. 9 In line with previous publications, administration of IVIG has led to a significant reduction in infection rate. 23 , 24 Despite the lack of IVIG-related adverse events in our series, however, the administration of IVIG might be associated with allergic reactions, acute renal failure, thrombotic events and hypertension.…”
Section: Discussionsupporting
confidence: 79%
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“…In nonrandomized clinical MANHATTAN trial, daratumumab/KRd (Dara-KRd, carfilzomib weekly) 100% of patients achieved ≥ VGPR, and 71% patients were MRD-negative. After 12 months, PFS and the OS rates were 98% and 100%, respectively [68]. The phase 2 FORTE trial compared KRd with followed ASCT (KRd_ASCT), 12 cycles of KRd (12), and carfilzomib, cyclophosphamide, and dexamethasone (KCd) with followed ASCT (KCd_ASCT).…”
Section: Lenalidomide For the Treatment Of Newly Diagnosed Multiple Myeloma In Patients Eligible For Asctmentioning
confidence: 99%