Smoldering Myeloma High-Risk Patient Observation and Longitudinal Insight Trial

Overview

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.

Interventions

• Other Patients with smoldering myeloma undergoing active surveillance with diffusion weighted whole body MRI.
  Patients with high-risk smoldering myeloma will be prospectively followed and chart review will be performed to determine if progression events happen, and how they happen. All patients on the study are recommended to undergo the following standard of care surveillance protocol: * Complete Blood Count (CBC), Complete Metabolic Panel (CMP), myeloma blood tests (serum kappa/lambda light chains, monoclonal protein evaluation, immunoglobulin levels), to be done monthly for first year, and then eve

Primary outcome measures

• 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. [Time frame: 2 years]

Secondary outcome measures (3)

• 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. [Time frame: 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. [Time frame: 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. [Time frame: 2 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Huntsman Cancer Institute at the University of Utah — Salt Lake City

Publications

• Cowan A, Ferrari F, Freeman SS, Redd R, El-Khoury H, Perry J, Patel V, Kaur P, Barr H, Lee DJ, Lightbody E, Downey K, Argyelan D, Theodorakakou F, Fotiou D, Liacos CI, Kanellias N, Chavda SJ, Ainley L, Sandecka V, Pospisilova L, Minarik J, Jungova A, Radocha J, Spicka I, Nadeem O, Yong K, Hajek R, Kastritis E, Marinac CR, Dimopoulos MA, Get G, Trippa L, Ghobrial IM. Personalised progression predic PMID 36858677
• Mateos MV, Kumar S, Dimopoulos MA, Gonzalez-Calle V, Kastritis E, Hajek R, De Larrea CF, Morgan GJ, Merlini G, Goldschmidt H, Geraldes C, Gozzetti A, Kyriakou C, Garderet L, Hansson M, Zamagni E, Fantl D, Leleu X, Kim BS, Esteves G, Ludwig H, Usmani S, Min CK, Qi M, Ukropec J, Weiss BM, Rajkumar SV, Durie BGM, San-Miguel J. International Myeloma Working Group risk stratification model for smolderi PMID 33067414
• Lakshman A, Rajkumar SV, Buadi FK, Binder M, Gertz MA, Lacy MQ, Dispenzieri A, Dingli D, Fonder AL, Hayman SR, Hobbs MA, Gonsalves WI, Hwa YL, Kapoor P, Leung N, Go RS, Lin Y, Kourelis TV, Warsame R, Lust JA, Russell SJ, Zeldenrust SR, Kyle RA, Kumar SK. Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J. 2018 Jun 12;8(6):59. doi: 10.1 PMID 29895887
• Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International PMID 25439696
• Thorsteinsdottir S, Gislason GK, Aspelund T, Rognvaldsson S, Oskarsson JThorn, Sigurethardottir GA, Thornorethardottir AR, Vietharsson B, Onundarson PT, Agnarsson BA, Sigurethardottir M, Thornorsteinsdottir I, Olafsson I, Eythornorsson E, Jonsson A, Berlanga O, Hultcrantz M, Durie BGM, Love TJ, Harding S, Landgren O, Kristinsson SY. Prevalence of smoldering multiple myeloma based on nationwide scr PMID 36747117
• Hillengass J, Moulopoulos LA, Delorme S, Koutoulidis V, Mosebach J, Hielscher T, Drake M, Rajkumar SV, Oestergaard B, Abildgaard N, Hinge M, Plesner T, Suehara Y, Matsue K, Withofs N, Caers J, Waage A, Goldschmidt H, Dimopoulos MA, Lentzsch S, Durie B, Terpos E. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myelom PMID 28841211
• Siontis B, Kumar S, Dispenzieri A, Drake MT, Lacy MQ, Buadi F, Dingli D, Kapoor P, Gonsalves W, Gertz MA, Rajkumar SV. Positron emission tomography-computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy. Blood Cancer J. 2015 Oct 23;5(10):e364. doi: 10.1038/bcj.2015.87. PMID 26495861
• Perez-Persona E, Vidriales MB, Mateo G, Garcia-Sanz R, Mateos MV, de Coca AG, Galende J, Martin-Nunez G, Alonso JM, de Las Heras N, Hernandez JM, Martin A, Lopez-Berges C, Orfao A, San Miguel JF. 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. PMID 17576818

Identifiers

NCT: NCT06212323 · HCI170107

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗