Heterogeneity of enrolment criteria for ongoing smouldering myeloma trials

Soomro, Mohammad Ahsen; Hoffman, James E.; Goodman, Aaron M.; Sborov, Douglas W.; Mohyuddin, Ghulam Rehman

doi:10.1111/bjh.18102

Cited by 7 publications

(4 citation statements)

References 10 publications

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“…9,[38][39][40][41] However, despite positive results observed in two phase III studies, treating patients with smoldering MM remains controversial. [42][43][44][45] If one of the reasons is offering unnecessary treatment in a few patients with high-risk smoldering MM and unexpectedly stable disease, it becomes paramount to identify such cases. Here, we showed in two independent series that approximately 18% of patients with smoldering MM have MGUSlike phenotype and very low risk of transformation.…”

Section: Discussionmentioning

confidence: 99%

Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance–Like Phenotype in Patients With Monoclonal Gammopathies

Burgos

Tamariz-Amador

Puig

et al. 2023

JCO

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PURPOSE The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)–like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated. PATIENTS AND METHODS An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis. RESULTS Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival. CONCLUSION We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.

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Section: Discussionmentioning

confidence: 99%

Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance–Like Phenotype in Patients With Monoclonal Gammopathies

Burgos

Tamariz-Amador

Puig

et al. 2023

JCO

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“…Only two are phase 3 and only one is placebo controlled. Only one has overall survival as an end point (DETER-SMM) 18 For the time being, patients with smoldering multiple myeloma should be enrolled in clinical trials but based on the current available evidence active therapy in practice cannot be justified.…”

Section: The Early Detection Of Skeletal Lesions Can Allow For Interv...mentioning

confidence: 99%

Quick consults in hematology: In support of active surveillance versus treatment of high‐risk smoldering multiple myeloma outside of a clinical trial

Gertz

2023

American J Hematol

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“…This is further exacerbated by heterogeneity of inclusion criteria in currently enrolling HR-SMM clinical trials. 13 A change in the diagnostic criteria of MM in 2014 led to patients who are asymptomatic with myeloma-defining biomarkers (≥60% plasma cells, a serum-free light chain involved-to-uninvolved ratio of ≥100 and/or >1 focal lesion detected via magnetic resonance imaging [MRI]) being classified as having MM despite the absence of end-organ damage. 9 These patients would have previously been considered to have ultrahigh-risk SMM.…”

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confidence: 99%