Shall we treat smoldering multiple myeloma in the near future?

Landgren, Ola

doi:10.1182/asheducation-2017.1.194

Cited by 28 publications

(17 citation statements)

References 47 publications

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“…Currently, two main approaches to SMM treatment are being investigated: eradication vs. control [29]. Several eradication-based studies have been conducted in patients with SMM.…”

Section: Discussionmentioning

confidence: 99%

Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS)

et al. 2020

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Current guidelines for smoldering multiple myeloma (SMM) recommend active monitoring until the onset of multiple myeloma (MM) before initiating treatment or enrollment in a clinical trial. Earlier intervention may delay progression to MM. In CENTAURUS, 123 patients with intermediate-risk or high-risk SMM were randomly assigned to daratumumab 16 mg/kg intravenously on extended intense (intense), extended intermediate (intermediate), or short dosing schedules. At the prespecified primary analysis (15.8-month median follow-up), the complete response (CR) rates (co-primary endpoint) were 2.4%, 4.9%, and 0% for intense, intermediate, and short dosing, respectively; the co-primary endpoint of CR rate >15% was not met. Progressive disease (PD)/death rates (number of patients who progressed or died divided by total duration of progression-free survival [PFS] in patient-years; co-primary endpoint) for intense, intermediate, and short dosing were 0.055 (80% confidence interval [CI], 0.014–0.096), 0.102 (80% CI, 0.044–0.160), and 0.206 (80% CI, 0.118–0.295), respectively, translating to a median PFS ≥24 months in all arms (P < 0.0001, <0.0001, and =0.0213, respectively). With longer follow-up (median follow-up, 25.9 months), CR rates were 4.9%, 9.8%, and 0% for intense, intermediate, and short dosing, respectively. PD/death rates for intense, intermediate, and short dosing were 0.059 (80% CI, 0.025–0.092), 0.107 (80% CI, 0.058–0.155), and 0.150 (80% CI, 0.089–0.211), respectively, again translating to a median PFS ≥ 24 months in all arms (P < 0.0001 for all arms). Twenty-four–month PFS rates were 89.9% (90% CI, 78.5–95.4%), 82.0% (90% CI, 69.0–89.9%), and 75.3% (90% CI, 61.1–85.0%) for intense, intermediate, and short dosing, respectively. Pharmacokinetic analyses indicated that intense dosing maintained target-saturating trough concentrations in most patients throughout weekly, every-2-week, and every-4-week dosing periods. No new safety signals were observed. These data provide the basis for an ongoing phase 3 study of daratumumab in SMM.

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“…Currently, two main approaches to SMM treatment are being investigated: eradication vs. control [29]. Several eradication-based studies have been conducted in patients with SMM.…”

Section: Discussionmentioning

confidence: 99%

Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS)

et al. 2020

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“…These cells often secrete large amounts of monoclonal Ig into the blood. This leads to a loss of structural integrity of the bone resulting in increased risk of bone fracture, as well as kidney damage due to the accumulation of monoclonal Ig deposits (70). In a study utilizing human MM cells, doxorubicin was used to model genotoxic stress.…”

Section: Hodgkin Lymphoma Non-hodgkin Lymphoma and Multiple Myelomamentioning

confidence: 99%

Targeting ADAM10 in Cancer and Autoimmunity

2020

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“…The cumulative probability of progression from SMM to MM is 73% at 15 years. 5 There is debate as to whether SMM is a condition to be treated as an early stage of MM 6 or simply observed, as with MGUS. To date, neither genomic sequencing nor expression profiling have identified a molecular predictor for patients with SMM who progress to MM.…”

Section: Challenges In Diagnosis and Managementmentioning

confidence: 99%

How We Approach Smoldering Multiple Myeloma

Raje

Yee

2020

JCO

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The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

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Shall we treat smoldering multiple myeloma in the near future?

Cited by 28 publications

References 47 publications

Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS)

Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS)

Targeting ADAM10 in Cancer and Autoimmunity

How We Approach Smoldering Multiple Myeloma

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