Smoldering Myeloma High-Risk Patient Observation and Longitudinal Insight Trial (SPOTLIGHT)

The purpose of this study is to define the natural history of high-risk smoldering myeloma in a modern cohort of patients undergoing close standard of care follow-up with diffusion weighted whole body magnetic resonance imaging.

Study Overview

• Status: Recruiting
• Conditions: Smoldering Multiple Myeloma
• Intervention / Treatment: Other: Patients with smoldering myeloma undergoing active surveillance with diffusion weighted whole body MRI.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Sharmilee Nuli; Phone Number: 801-585-0255; Email: Sharmilee.Nuli@hci.utah.edu

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute at the University of Utah
      • Contact: Bailee Daniels; Phone Number: 801-587-4699; Email: Bailee.Daniels@hci.utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Smoldering myeloma (SMM)

Description

Inclusion Criteria:

• Adult subject aged ≥ 18 years.

• Diagnosis of smoldering myeloma as per the IMWG criteria, specifically:

  • Serum monoclonal protein (IgG or IgA) of 30g/L or greater per 24 hours or urinary monoclonal protein of 500mg or greater per 24 hours and/or
  • Clonal bone marrow plasma cells 10-59% with the absence of myeloma-defining events or amyloidosis

• High-risk smoldering myeloma defined as two or more out of four of the following criteria:

  • M-spike greater than 2 g/dL
  • An involved/uninvolved free light chain ratio greater than 20
  • Bone marrow plasmacytosis greater than 20%
  • Presence of any of translocation (4;14), deletion 17p, deletion 13q or 1q gain by conventional cytogenetics/fluorescence in situ hybridization (FISH) studies) and/or
  • An IMWG SMM score of 9 or greater according to the IMWG risk model for smoldering multiple myeloma (SMM)
• Diagnosis of high-risk SMM made within 365 days of enrollment in the study. Note: If a patient previously had MGUS or low/intermediate SMM- the date at which high-risk SMM was diagnosed would have to be within 365 days of enrollment in the study.

Exclusion Criteria:

• Presence of any features that would meet diagnostic criteria for myeloma as per the IMWG Criteria
• Presence of extramedullary plasmacytomas
• Presence of any focal bone marrow lesions, or lytic bone lesions on imaging done prior to screening or on screening. However, presence of diffuse or patchy infiltration of the marrow (without any clear lesions) on MRI, will not be an exclusion criteria. Patients with 1 focal marrow lesion on MRI that is attributable to plasma cell dyscrasia, will be excluded from study, even if they do not meet criteria for myeloma. Patients with 1 focal marrow lesion can only be enrolled if the lesion does not appear to be related to myeloma, based on the judgement of the investigator. Use of restricted diffusion and ADC values can assist in ascertainment.
• Creatinine clearance of less than 40ml/min.
• Presence of AL Amyloidosis (the amount of workup necessary to exclude AL Amyloidosis is per the discretion of the treating investigator, however the investigator must attest that they do not believe AL Amyloidosis to be present at time of enrollment. Serum nt-PROBNP is recommended as part of evaluation in order to ascertain for cardiac amyloidosis).

Note: The Hgb cut-offs can vary between institutions (lower cut-off for Hgb University of Utah for men is a Hgb of 14.8, rendering a patient with Hgb of 12.7 as having a CRAB feature). If the Hgb is above 10g/dl but the patient meets the definition of anemia according to the IMWG criteria, by virtue of this being more than 2 g/dl below the limit of normal, the investigator can decide whether to call a patient being considered for screening as having multiple myeloma OR smoldering myeloma and allow enrollment on this study.

Given that the values used to define high-risk SMM can change, at time of enrollment, if utilizing at least 2/4 of the 2/20/20+cytogenetics criteria to enroll, participants should meet at least 2/4 of the 2/20/20. If participants had met at least 2/4 previously at some timepoint but do not meet at least 2/4 currently, they cannot be enrolled in the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of morbid progression events attributable to a plasma cell dyscrasia at two years, with morbid events defined as: death, renal injury that does not reverse, fracture, lytic bone lesion, AL Amyloidosis or plasma cell leukemia.	Frequency and nature of progression events in a prospective cohort of patients with smoldering myeloma undergoing active surveillance with diffusion weighted whole body MRI	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the quality of life as measured by physical function domain on the PROMIS-29 (Patient-Reported Outcomes Measurement Information System), from baseline to the end of study at 24 months of follow-up.	Determine longitudinal Quality of Life as assessed by the PROMIS-29 instrument. The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of physical function.	2 years
Change in the quality of life as measured by pain interference domain on the PROMIS-29 (Patient-Reported Outcomes Measurement Information System), from baseline to the end of study at 24 months of follow-up.	Determine longitudinal Quality of Life as assessed by the PROMIS-29 instrument. The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of pain interference.	2 years
Change in the quality of life as measured by anxiety domain on the PROMIS-29 (Patient-Reported Outcomes Measurement Information System), from baseline to the end of study at 24 months of follow-up.	Determine longitudinal Quality of Life as assessed by the PROMIS-29 instrument. The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of anxiety.	2 years

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Ghulam Rehman Mohyuddin, MD, Huntsman Cancer Institute

Publications and helpful links

General Publications

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
• Cowan A, Ferrari F, Freeman SS, et al: Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study. Lancet Haematol 10:e203-e212, 2023
• Mateos MV, Kumar S, Dimopoulos MA, et al: International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J 10:102, 2020
• Lakshman A, Rajkumar SV, Buadi FK, et al: Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J 8:59, 2018
• Rajkumar SV, Dimopoulos MA, Palumbo A, et al: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538-48, 2014
• Thorsteinsdottir S, Gislason GK, Aspelund T, et al: Prevalence of smoldering multiple myeloma based on nationwide screening. Nat Med 29:467-472, 2023
• Hillengass J, Moulopoulos LA, Delorme S, et al: Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group. Blood Cancer J 7:e599, 2017
• Siontis B, Kumar S, Dispenzieri A, et al: Positron emission tomography- computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy. Blood Cancer J 5:e364, 201
• Perez-Persona E, Vidriales MB, Mateo G, et al: New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 110:2586-92, 2007
• Dispenzieri A, Kyle RA, Katzmann JA, et al: Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 111:785-9, 2008
• Hill E, Dew A, Morrison C, et al: Assessment of Discordance Among Smoldering Multiple Myeloma Risk Models. JAMA Oncol 7:132-134, 2021
• Lonial S, Jacobus S, Fonseca R, et al: Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma. J Clin Oncol 38:1126-1137, 2020
• Mateos MV, Hernandez MT, Giraldo P, et al: Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 369:438-47, 2013
• Mateos MV, Hernandez MT, Salvador C, et al: Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study. Eur J Cancer 174:243-250, 2022
• Wennmann M, Goldschmidt H, Mosebach J, et al: Whole-body magnetic resonance imaging plus serological follow-up for early identification of progression in smouldering myeloma patients to prevent development of end-organ damage. Br J Haematol 199:65-75, 2022
• Hays RD, Spritzer KL, Schalet BD, et al: PROMIS((R))-29 v2.0 profile physical and mental health summary scores. Qual Life Res 27:1885-1891, 2018
• Hays RD, Spritzer KL, Schalet BD, et al: PROMIS(®)-29 v2.0 profile physical and mental health summary scores. Qual Life Res 27:1885-1891, 2018

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Hematologic Diseases; Immunoproliferative Disorders; Precancerous Conditions; Paraproteinemias; Blood Protein Disorders; Hypergammaglobulinemia; Hemic and Lymphatic Diseases; Smoldering Multiple Myeloma
• Other Study ID Numbers: HCI170107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No