The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype

Schinke, Carolina; Hoering, Antje; Wang, Hongwei; Carlton, Victoria; Thanandrarajan, Sharmilan; Deshpande, Shayu; Patel, Purvi; Molnár, Gábor Tamás; Susanibar, Sandra; Mohan, Meera; Mathur, Pankaj; Radhakrishnan, M.; Hoque, Shadiqul; Kamimoto, Jorge Jo; Grazziutti, Monica; Rhee, Frits van; Zangari, Maurizio; Insuasti-Beltran, Giovanni; Alapat, Daisy; Post, Ginell R.; Yaccoby, Shmuel; Epstein, Joshua; Rasche, Leo; Johnson, Sarah K.; Moorhead, Martin; Willis, Thomas A.; Barlogie, Bart; Walker, Brian A.; Weinhold, Niels; Davies, Faith E.; Morgan, Gareth J.

doi:10.3324/haematol.2017.165217

Cited by 27 publications

(30 citation statements)

References 14 publications

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“…This regimen drastically reduced the patient's tumor burden, which in turn lead to an improved renal function. Remarkably, the patient achieved a stringently defined complete remission (sCR) two months after the initiation of venetoclax/daratumumab/dexamethasone, and also had no evidence of minimal residual disease at 1 myeloma cell in 10 5 cells, measured by eight color flow‐cytometry as previously reported, 4 months into therapy, Figure E and F. He continues to be in a sCR after 10 months of therapy.…”

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confidence: 69%

The combination of venetoclax, daratumumab and dexamethasone for the treatment of refractory primary plasma cell leukemia

2019

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E34 CORRESPONDENCE 1-4, thalidomide 100 mg p.o. daily days1-21, doxorubicin 10 mg/m 2 daily on days 1-4, cyclophosphamide 400 mg/m 2 daily on days 1-4, and etoposide 40 mg/m 2 daily on days 1-4).A 74-year-old male was admitted to the UAMS inpatient service with complaints of generalized malaise and fatigue, and decreased urine output. Complete blood count revealed severe anemia with a hemoglobin level of 7.7 g/dL, and a creatinine level of 4.7 mg/dL, with a Glomerular Filtration Rate of 12.2 mL/min/1.73 m 2 . Peripheral smear showed circulating plasma cells, Figure 1A. This was further confirmed by flow-cytometry (54% circulating plasma cells in peripheral blood).Additional work up revealed markedly elevated lambda light chains of 1800 mg/dL. Bone marrow (BM) biopsy revealed 90% plasma cells positive for CD138, Figure 1B,C. Flourescence in situ hybridization was positive for translocation t(11:14) (95%) and a deletion 17p in 25%. His immunoglobulins, including IgG, IgA and IgM were all suppressed, and immunofixation in the serum and urine was positive for lambda light chains. The patient presented with 8 g proteinuria, which was predominantly due to increased urinary light chain excretion (Urine M-protein = 7.4 g/dL), suggestive for light chain cast nephropathy as a cause of the patient's renal compromise. The patient's albumin at presentation was

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confidence: 69%

The combination of venetoclax, daratumumab and dexamethasone for the treatment of refractory primary plasma cell leukemia

2019

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“…In a post hoc analysis from ASPIRE, carfilzomib provided greater responses and improvements in PFS at 18 months and cumulative ≥CR rates increased over time suggesting that there may benefit of continued carfilzomib treatment [ 15 ]. However, the degree of association may be different depending on patient and disease factors, and specific treatments received [ 34 – 37 ]. A large meta-analysis of data from 102 studies involving 13 322 patients with RRMM indicated a correlation between the rate of VGPR or better and median PFS ( R 2 = 0.63) [ 38 ].…”

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confidence: 99%

Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR

et al. 2020

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To understand the profile of best responders (complete response or better [≥CR]) to carfilzomib, we described the characteristics, progression-free survival (PFS), overall survival (OS) data, and the safety of patients who achieved ≥CR to carfilzomib-based treatment in ASPIRE and ENDEAVOR. In post hoc analyses from ASPIRE and ENDEAVOR, median PFS and OS were longer for ≥CR patients versus those who achieved a very good partial response or partial response (VGPR/PR). In the carfilzomib arm of ASPIRE, median PFS was 50.4 months for ≥CR versus 22.1 months for VGPR/PR; median OS was 67.0 versus 44.2 months, respectively. In the carfilzomib arm of ENDEAVOR, median PFS was 34.0 for ≥CR versus 20.4 months for VGPR/PR; median OS was non-estimable. Despite the longer treatment duration, fewer patients with ≥CR versus VGPR/PR experienced treatment-emergent adverse events that led to discontinuation of carfilzomib-based treatment in ASPIRE or ENDEAVOR. Low serum lactate dehydrogenase was the only factor associated with achieving ≥CR vs patients not achieving CR in ASPIRE in multivariate regression analyses. No association was found between cytogenetic risk status and reaching ≥CR. Carfilzomib treatment may lead to rapid and deep responses, irrespective of most patient characteristics.

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“…For the flow-cytometric assessment of MRD, BM samples were immunophenotyped on a FACSCanto II flow cytometer using an 8-color technique [CD138 (V-500), CD38 (FITC), CD19 (PE-Cy7), CD45 (V-450), CD27 (PercpCy5.5), CD81 (APC-H-7), CD56 (APC) and CD20 (PE)] 4 . Acquiring at least 2.5×10 6 events, we defined MRD negativity by Flow as less than 20 events indicating phenotypically aberrant clonal plasma cells.…”

Section: Methodsmentioning

confidence: 99%

Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma

et al. 2018

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The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in Multiple Myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy, for whom MRD flow-cytometry and the two imaging modalities positron-emission-tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET-positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.

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The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype

Cited by 27 publications

References 14 publications

The combination of venetoclax, daratumumab and dexamethasone for the treatment of refractory primary plasma cell leukemia

The combination of venetoclax, daratumumab and dexamethasone for the treatment of refractory primary plasma cell leukemia

Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR

Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma

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