Introduction
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder associated with a high risk of progression to multiple myeloma (MM) [ 1 , 2 ]. The estimated incidence of SMM was 0.4 to 0.9 per 100 000 in 2016 [ 3 , 4 ]; the prevalence of SMM in people ≥40 years old was 0.53% in 2023 [ 5 ]. The incidence of clinically detected SMM was 1.4 per 100 000 in the general population and 2.8 per 100 000 for people ≥40 years old in 2021 [ 6 ]. Approximately one in seven patients with MM in the USA are smoldering at diagnosis [ 4 ]. The 2‑, 5‑, and 10-year risk of SMM progression to MM is 22%, 42%, and 64%, with the median time to progression of 6.4 years [ 7 ]; in addition, the overall risk of progression is 10% per year in the first 5 years, 3% per year for years 6 to 10, and 1% per year thereafter [ 8 ].
In clinical practice, risk stratification aims to identify patients with SMM and a 50% or greater risk of progression to MM within 2 years [ 1 ]. The current standard of care (SOC) for SMM is active monitoring until progression or until patients fulfill criteria for high-risk (HR)-SMM [ 2 , 9 ]. The National Comprehensive Cancer Network® Guidelines for Multiple Myeloma recommend participating in clinical trials or monitoring all patients with SMM or using daratumumab or lenalidomide for selected patients with HR-SMM [ 10 ]. Nonetheless, clinical trial data suggest that early treatment may delay disease progression to MM [ 11–13 ]. Follow-up should be tailored to individual needs and, in part, based on risk of progression [ 1 , 9 , 10 ]. In July 2025, daratumumab became the first approved treatment by the European Medicines Agency for HR-SMM [ 14 ].
Treatment of SMM is an active area of clinical research, with ≥40 interventional studies ongoing as of June 2025 [ 15 ]. Despite the high level of interest and patient-preference studies in MM [ 16–22 ], there are scarce data documenting the potential physical and psychological effects associated with a diagnosis of HR-SMM and patients’ treatment experiences [ 23–25 ]. Exploring patient experiences with or without treatment can inform unmet needs, perceptions of safety, and the benefit-risk trade-off a treatment must offer to be acceptable to patients [ 26 ]. We conducted this study aiming to understand patient experiences and perceptions after their HR-SMM diagnosis in those with HR-SMM or MM progressed from HR-SMM, including the impact and burden associated with the diagnosis as well as patients’ assessments of treatment attributes and the decision-making processes relating to treatment selection. We also estimated the minimum progression-free survival (min-PFS) required for patients to accept treatment risks and disease burden.
Methods
Study design
This was a non-interventional, observational, mixed-methods study in patients with HR-SMM or newly diagnosed MM, including those with a previous diagnosis of HR-SMM (referred to as MM throughout). We started the study with a targeted literature review to support hypothesis generation and then conducted semi-structured, qualitative interviews that included a quantitative thresholding task.
This study was conducted in accordance with International Council for Harmonization guidelines, preference-based methods from the International Society for Pharmacoeconomics and Outcomes Research, and other applicable requirements and guidelines [ 27–31 ]. The protocol was approved by a central institutional review board in the US (Salus; Ethics & Inclusion Study Number 22116-01, approved on 14 June 2022). This type of research, characterized by recruitment outside clinical settings, qualifies as low-risk market research and was determined eligible for ethics exemption for the multi-country submission, covering all four participating countries.
Targeted literature review
The literature review identified available information (2016 to early 2022) about patient experience and burden of being diagnosed with SMM or MM. It provided evidence for the key concepts to explore in the interview and the attributes to include in the thresholding exercise (for details, see Supplemental Materials, Supplemental Figure S1, Supplemental Table S1).
Findings from the literature review [ 17 , 32–34 ] and the knowledge from clinical studies led to three hypotheses: 1) patients with HR-SMM worry about disease progression; 2) patients with HR-SMM or MM prefer treatment at the SMM stage (as opposed to no treatment) and are willing to tolerate adverse effects if treatment delays disease progression to MM; and 3) patients with HR-SMM are less aware of treatment options compared with patients with MM. These hypotheses were used to structure the interview guides and refine the thresholding exercise.
Patient population
Patients with a diagnosis of HR-SMM or MM who recently progressed from HR-SMM were recruited in a 1:1 ratio in Spain, Italy, France, and the USA to participate in a one-on-one, semi-structured virtual interview. Patients were identified through physician referrals, recruiter databases, patient association referrals, and social media groups. Screening and recruiting were conducted by an independent specialist research recruitment company, who identified candidates via clinician referrals and patient panels, conducted screening by phone or online, and invited confirmed eligible candidates to participate.
Inclusion criteria were age ≥18 years, diagnosis of HR-SMM (≥30 days before screening) or MM (<1 year before screening) with a prior diagnosis of HR-SMM (<2 years before screening), and ability to read, speak, and understand their local language (i.e., Spanish, Italian, French, or English). HR-SMM was diagnosed per the International Myeloma Working Group (IMWG) 20/2/20 or Mayo Clinic 20/2/20 risk stratification criteria [ 35 , 36 ]. History of non-MM malignancy or amyloidosis <1 year of screening and current enrollment in a clinical trial of an SMM or MM treatment were key exclusion criteria (Supplemental Table S2).
Following confirmation of diagnosis, subjects were provided with the web link for an electronic consent form, and researchers and participants agreed on a date and time for the interview. The electronic consent form was approved by Salus IRB (No. 22116-01A to -02) and informed the participant about the requirements, risks, and expectations from their participation as well as the data collection, data privacy, and storage procedures to protect anonymity and ensure data protection following GDPR and HIPAA standards or legal data protection requirements. Voluntary consent from participants was documented and all legal data protection requirements were followed. Participants were able to print a PDF version of the consent, giving them enough time to read and consider the study specifics. Consent to take part in the audio-recorded interview was also confirmed verbally at the start of each interview.
Qualitative interviews and threshold exercise
Interviews were conducted by expert interviewers who followed a guide to ensure all concepts of interest were discussed in a standard sequence. Discussions focused on clinical history and disease awareness, signs and symptoms, impacts of the diagnosis on life, and perceptions of and experiences with treatments. Patients also completed a sociodemographic form and the functional scales of the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC-QLQ-C30) questionnaire (not the complete questionnaire).
In the last part of the interview, patients were asked to complete a thresholding exercise in which they reviewed descriptions of a hypothetical treatment for HR-SMM and indicated their preference for treatment versus no treatment to elicit the min-PFS they would require to accept the hypothetical treatment profile (Supplemental Figure S2). The no-treatment option involved doctor appointments every 2 months (active monitoring, SOC) with a PFS of 38 months [ 11 , 37 ]. The hypothetical treatment included a detailed subcutaneous administration schedule and a 42% risk of any grade adverse events (AEs). The rate for AE risk was conservatively selected on the basis of clinical trial data (for example, the most common reported AE with daratumumab in a phase II trial was fatigue occurring at a frequency of 41.5% [ 11 ]). The min-PFS started at 70 months and varied systematically in subsequent treatment-choice questions according to patient choices to capture their willingness to take treatment for HR-SMM and tolerate related treatment burden (that is, treatment administration and risk of side effects) for a given increase in PFS. This design facilitated establishing the min-PFS (that is, the minimum number of months of PFS required to compensate for treatment administration and side effects) for the hypothetical treatment from 40 to 100 months with a 2-month precision (for example, 52–54 months) by asking each patient 5 treatment-choice questions.
Sample size determination
For most studies aiming to understand common perceptions and experiences, 12 interviews from a relatively homogeneous group of participants would provide sufficient information, and the basic meta theme elements were observed with 6 interviews [ 38 ]. Therefore, the current study enrolled 50 patients in total, with n = 12 each in France, Italy, and Spain, and n = 14 in the USA. This sample size was sufficient to capture all relevant concepts at the country level with data saturation (i.e., the point when no new information or themes are observed).
Because patients with HR-SMM or MM who progressed from HR-SMM were recruited at a 1:1 ratio, our sample (≥20 patients/group) sought to facilitate comparison between these two groups for quantitative data.
Data analysis
Voice recordings were fully transcribed in English for further analysis. Transcripts were anonymized and cleaned of personal identifiable information. A trained team coded each transcript using Atlas.ti version 22 (ATLAS.ti Scientific Software Development, GmbH) guided by a pre-defined coding dictionary based on expected themes from the interview guide. To establish inter-coder reliability, four coders independently coded the first five transcripts (10%), resolving discrepancies through discussion until >70% coder agreement was achieved. All coding was conducted blind to participants’ thresholding task responses. Code frequency counts and verbatim narrative data (i.e., patient quotes) associated with each code were quality-checked, critically analyzed, and summarized. All symptom data were derived from patient self-report and were not clinically verified; they therefore reflect patient perception and awareness of their condition rather than confirmed diagnoses.
Quantitative data from the sociodemographic form and the EORTC-QLQ-C30 were summarized using descriptive statistics overall and by subgroup (HR-SMM and MM). The findings were summarized in aspects (the same as in interview conduction) including impact on daily functioning, physical impact (ability to sleep, energy/tiredness/fatigue levels, motor coordination/sequential bodily movements, and pain), psychological impact (anxiety or worry/fear, depression or sadness, other emotions such as anger and hopelessness), cognitive impact, social impact, work (occupational) impact, financial impact, family impact, and impact on future perspectives/planning.
Results of the thresholding exercises were summarized using descriptive statistics for all patients, and by HR-SMM and MM groups. Missing data were coded as missing and not imputed.
Results
Patient disposition and characteristics
Fifty-two patients completed the interview, and 2 were excluded (1 owing to thresholding exercise amendments after the interview, and 1 owing to significant disease progression by the time of interview); thus, 50 were included in the analysis with a 1:1 distribution between patients with HR-SMM and MM (Supplemental Figure S3).
The 50 interviews were conducted between 19 October 2022, and 6 June 2023. The mean age of the study sample was 57.6 years (HR-SMM, 59.6 [range, 37–79]; MM, 55.6 [range, 39–75]), and 56% of the patients were female. Forty-six patients had physician-provided Eastern Cooperative Oncology Group (ECOG) score, of whom 71% (17/24) with HR-SMM and 23% (5/22) with MM scored 0; however, no patients with HR-SMM and 9% (2/22) with MM scored 3 ( Table 1 ). Table 1. Sociodemographic and clinical characteristics. Characteristic Overall ( N = 50) High-risk SMM ( n = 25) MM ( n = 25) Age, mean (SD), years 57.6 (12.1) 59.6 (12.9) 55.6 (11.1) Female, n (%) 28 (56.0) 13 (52.0) 15 (60.0) Country of residency (screening), n (%) USA 14 (28.0) 7 (28.0) 7 (28.0) Italy 12 (24.0) 6 (24.0) 6 (24.0) Spain 12 (24.0) 6 (24.0) 6 (24.0) France 12 (24.0) 6 (24.0) 6 (24.0) Ethnic background (for USA only), n (%) Hispanic or Latino 1 (7.1) 0 1 (14.3) Not Hispanic or Latino 12 (85.7) 6 (85.7) 6 (85.7) Preferred not to say 1 (7.1) 1 (14.3) 0 Race (for USA only), n (%) White 9 (64.3) 4 (57.1) 5 (71.4) Black/African American or Black/African/Caribbean/Black British 3 (21.4) 2 (28.6) 1 (14.3) Prefer not to say 2 (14.3) 1 (14.3) 1 (14.3) Living alone, n (%) Yes 8 (16.0) 6 (24.0) 2 (8.0) No (ie, living with spouse, relative[s], friend[s], nursing home) 42 (84.0) 19 (76.0) 23 (92.0) Employment status, n (%) Full-time employment 10 (20.0) 6 (24.0) 4 (16.0) Part-time employed 3 (6.0) 2 (8.0) 1 (4.0) Self-employed 7 (14.0) 4 (16.0) 3 (12.0) Homemaker 9 (18.0) 5 (20.0) 4 (16.0) Retired 16 (32.0) 8 (32.0) 8 (32.0) Unemployed 2 (4.0) 0 2 (8.0) On sick leave 2 (4.0) 0 2 (8.0) Not able to work due to disability 1 (2.0) 0 1 (4.0) Educational degree, n (%) Elementary/primary school or GCSE/O levels or equivalent 4 (8.0) 2 (8.0) 2 (8.0) High school or A levels or equivalent 8 (16.0) 2 (8.0) 6 (24.0) Some college/university or vocational/work-based qualifications 8 (16.0) 7 (28.0) 1 (4.0) College/university (BA, BS) 23 (46.0) 8 (32.0) 15 (60.0) Master’s degree 4 (8.0) 3 (12.0) 1 (4.0) Doctoral degree (MD, PhD, PharmD) 2 (4.0) 2 (8.0) 0 Other 1 (2.0) 1 (4.0) 0 Type of health insurance, n (%) Employer-provided insurance 6 (12.0) 4 (16.0) 2 (8.0) Self-provided private insurance 18 (36.0) 9 (36.0) 9 (36.0) National insurance (EU countries only) 32 (64.0) 14 (77.8) 18 (100.0) Medicare (USA only) 2 (4.0) 1 (14.3) 1 (14.3) Medicaid (USA only) 0 0 0 Other (USA only) 2 (4.0) 1 (14.3) 1 (14.3) Veterans Affairs/military healthcare (USA only) 0 0 0 None (USA only) 0 0 0 ECOG score, n (%)* 0 22 (44.0) 17 (68.0) 5 (20.0) 1 17 (34.0) 6 (24.0) 11 (44.0) 2 5 (10.0) 1 (4.0) 4 (16.0) 3 2 (4.0) 0 2 (8.0) 4 0 0 0 Missing ECOG score 4 (8.0) 1 (4.0) 3 (12.0) Taken (or taking) medication for SMM, n (%) No 44 (88.0) 23 (92.0) 21 (84.0) Yes 6 (12.0) 2 (8.0) 4 (16.0) If yes, medication taken (or taking) for SMM, n (%) Bortezomib 4 (66.7) 1 (50.0) † 3 (75.0) † Daratumumab 4 (66.7) 2 (100.0) † 2 (50.0) † Other 1 (16.7) 1 (50.0) † 0 † Dexamethasone 4 (66.7) 1 (50.0) † 3 (75.0) † Thalidomide 1 (16.7) 1 (50.0) † 0 † Lenalidomide 4 (66.7) 0 † 4 (100.0) † Length of period taking medication for SMM, n (%) >6 months 5 (83.3) 1 (50.0) 4 (100.0) 6 months to <1 year 1 (16.7) 1 (50.0) 0 1 year to <3 years 0 0 0 ≥3 years 0 0 0 *ECOG score definitions: 0 - Fully active, able to carry on all pre-disease performance without restriction; 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work); 2 - Ambulatory and capable of all self‑care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 - Capable of only limited self‑care, confined to bed or chair more than 50% of waking hours; 4 - Completely disabled. Cannot carry on any self‑care. Totally confined to bed or chair. †Row sum was used as the denominator. Abbreviations: ECOG: Eastern Cooperative Oncology Group; MM: multiple myeloma; SMM: smoldering MM.
Table 1.
Sociodemographic and clinical characteristics.
*ECOG score definitions: 0 - Fully active, able to carry on all pre-disease performance without restriction; 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work); 2 - Ambulatory and capable of all self‑care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 - Capable of only limited self‑care, confined to bed or chair more than 50% of waking hours; 4 - Completely disabled. Cannot carry on any self‑care. Totally confined to bed or chair. †Row sum was used as the denominator. Abbreviations: ECOG: Eastern Cooperative Oncology Group; MM: multiple myeloma; SMM: smoldering MM.
| Characteristic | Overall ( N = 50) | High-risk SMM ( n = 25) | MM ( n = 25) |
| Age, mean (SD), years | 57.6 (12.1) | 59.6 (12.9) | 55.6 (11.1) |
| Female, n (%) | 28 (56.0) | 13 (52.0) | 15 (60.0) |
| Country of residency (screening), n (%) | |||
| USA | 14 (28.0) | 7 (28.0) | 7 (28.0) |
| Italy | 12 (24.0) | 6 (24.0) | 6 (24.0) |
| Spain | 12 (24.0) | 6 (24.0) | 6 (24.0) |
| France | 12 (24.0) | 6 (24.0) | 6 (24.0) |
| Ethnic background (for USA only), n (%) | |||
| Hispanic or Latino | 1 (7.1) | 0 | 1 (14.3) |
| Not Hispanic or Latino | 12 (85.7) | 6 (85.7) | 6 (85.7) |
| Preferred not to say | 1 (7.1) | 1 (14.3) | 0 |
| Race (for USA only), n (%) | |||
| White | 9 (64.3) | 4 (57.1) | 5 (71.4) |
| Black/African American or Black/African/Caribbean/Black British | 3 (21.4) | 2 (28.6) | 1 (14.3) |
| Prefer not to say | 2 (14.3) | 1 (14.3) | 1 (14.3) |
| Living alone, n (%) | |||
| Yes | 8 (16.0) | 6 (24.0) | 2 (8.0) |
| No (ie, living with spouse, relative[s], friend[s], nursing home) | 42 (84.0) | 19 (76.0) | 23 (92.0) |
| Employment status, n (%) | |||
| Full-time employment | 10 (20.0) | 6 (24.0) | 4 (16.0) |
| Part-time employed | 3 (6.0) | 2 (8.0) | 1 (4.0) |
| Self-employed | 7 (14.0) | 4 (16.0) | 3 (12.0) |
| Homemaker | 9 (18.0) | 5 (20.0) | 4 (16.0) |
| Retired | 16 (32.0) | 8 (32.0) | 8 (32.0) |
| Unemployed | 2 (4.0) | 0 | 2 (8.0) |
| On sick leave | 2 (4.0) | 0 | 2 (8.0) |
| Not able to work due to disability | 1 (2.0) | 0 | 1 (4.0) |
| Educational degree, n (%) | |||
| Elementary/primary school or GCSE/O levels or equivalent | 4 (8.0) | 2 (8.0) | 2 (8.0) |
| High school or A levels or equivalent | 8 (16.0) | 2 (8.0) | 6 (24.0) |
| Some college/university or vocational/work-based qualifications | 8 (16.0) | 7 (28.0) | 1 (4.0) |
| College/university (BA, BS) | 23 (46.0) | 8 (32.0) | 15 (60.0) |
| Master’s degree | 4 (8.0) | 3 (12.0) | 1 (4.0) |
| Doctoral degree (MD, PhD, PharmD) | 2 (4.0) | 2 (8.0) | 0 |
| Other | 1 (2.0) | 1 (4.0) | 0 |
| Type of health insurance, n (%) | |||
| Employer-provided insurance | 6 (12.0) | 4 (16.0) | 2 (8.0) |
| Self-provided private insurance | 18 (36.0) | 9 (36.0) | 9 (36.0) |
| National insurance (EU countries only) | 32 (64.0) | 14 (77.8) | 18 (100.0) |
| Medicare (USA only) | 2 (4.0) | 1 (14.3) | 1 (14.3) |
| Medicaid (USA only) | 0 | 0 | 0 |
| Other (USA only) | 2 (4.0) | 1 (14.3) | 1 (14.3) |
| Veterans Affairs/military healthcare (USA only) | 0 | 0 | 0 |
| None (USA only) | 0 | 0 | 0 |
| ECOG score, n (%)* | |||
| 0 | 22 (44.0) | 17 (68.0) | 5 (20.0) |
| 1 | 17 (34.0) | 6 (24.0) | 11 (44.0) |
| 2 | 5 (10.0) | 1 (4.0) | 4 (16.0) |
| 3 | 2 (4.0) | 0 | 2 (8.0) |
| 4 | 0 | 0 | 0 |
| Missing ECOG score | 4 (8.0) | 1 (4.0) | 3 (12.0) |
| Taken (or taking) medication for SMM, n (%) | |||
| No | 44 (88.0) | 23 (92.0) | 21 (84.0) |
| Yes | 6 (12.0) | 2 (8.0) | 4 (16.0) |
| If yes, medication taken (or taking) for SMM, n (%) | |||
| Bortezomib | 4 (66.7) | 1 (50.0) † | 3 (75.0) † |
| Daratumumab | 4 (66.7) | 2 (100.0) † | 2 (50.0) † |
| Other | 1 (16.7) | 1 (50.0) † | 0 † |
| Dexamethasone | 4 (66.7) | 1 (50.0) † | 3 (75.0) † |
| Thalidomide | 1 (16.7) | 1 (50.0) † | 0 † |
| Lenalidomide | 4 (66.7) | 0 † | 4 (100.0) † |
| Length of period taking medication for SMM, n (%) | |||
| >6 months | 5 (83.3) | 1 (50.0) | 4 (100.0) |
| 6 months to <1 year | 1 (16.7) | 1 (50.0) | 0 |
| 1 year to <3 years | 0 | 0 | 0 |
| ≥3 years | 0 | 0 | 0 |
All 14 patients (100%) from the USA were diagnosed by chance and were asymptomatic when their blood was screened for other reasons, whereas 17 patients (47%) from Europe were diagnosed by chance, and the rest were diagnosed after reporting symptoms.
Six patients (6/50, 12%) took a medication during the SMM phase, four of whom had progressed to MM and two still had HR-SMM. Medications taken alone or in combination during the SMM phase were bortezomib (HR-SMM, n = 1; MM, n = 3), daratumumab (HR-SMM, n = 2; MM, n = 2), dexamethasone (HR-SMM, n = 1; MM, n = 3), and lenalidomide (MM, n = 4) ( Table 1 ). One patient from France reported that SMM treatment was not yet available in their country at the time of their diagnosis, reflecting country-level variation in access to treatment options.
Disease awareness
Most patients understood SMM as a precursor to MM, but their understanding of SMM, HR-SMM, and MM was variable; 10 patients (20%) were unaware of a distinction between HR-SMM and SMM. All patients had a clinician-confirmed diagnosis of HR-SMM or MM; however, 10 patients (10/50, 20%) expressed that they were unaware of the term HR-SMM during the interview. Much of their understanding of the disease was based on the explanation provided by their clinician. Two patients mentioned other sources, such as a conference or independent research.
Symptoms associated with HR-SMM and MM
Ten patients (10/50, 20%) were asymptomatic when interviewed (HR-SMM, n = 8; MM, n = 2), meaning 80% of the combined HR-SMM and MM sample reported at least one symptom. Tiredness/fatigue ( n = 34; 68% of total, 85% of symptomatic) and pain ( n = 28; 56% of total, 70% of symptomatic) were the most frequently reported symptoms ( Figure 1 , patient quotes in Table 2 ). Tiredness/fatigue was also reported as the most bothersome symptom among 41% (14/34) of those affected by it; 36% (10/28) of those affected by pain and 28% (5/18) affected by weakness reported pain and weakness, respectively, as the most bothersome symptom. For tiredness/fatigue, patients also described the intensity ( n = 9; e.g., strong, very much, overwhelming) or frequency ( n = 3; e.g., chronic, a few days per week, during the day), or both ( n = 8; e.g., too tired all the time, always very tired, persistent tiredness every day). For pain, ≥50% of patients mentioned back pain. Figure 1. Symptoms reported by patients. Horizontal bar graph of symptoms. Legend: Symptoms described as most bothersome; Symptoms experienced. X-axis label: Percentage of patients, left parenthesis N equals 50 right parenthesis, unit percent, range 0 to 100. Y-axis label: symptom categories. Values shown as percent labels on bars. Tiredness or fatigue: most bothersome 28 percent; experienced 68 percent. Pain: most bothersome 20 percent; experienced 56 percent. Other asterisk: most bothersome 4 percent; experienced 52 percent. Weakness: most bothersome 10 percent; experienced 36 percent. Anemia: most bothersome 2 percent; experienced 20 percent. Loss of appetite: most bothersome 2 percent; experienced 16 percent. Tingling: most bothersome 0 percent; experienced 16 percent. Balance: most bothersome 0 percent; experienced 12 percent. Constipation: most bothersome 2 percent; experienced 10 percent. Sense: most bothersome 0 percent; experienced 6 percent. Asymptomatic: most bothersome 0 percent; experienced 20 percent. Bar graph showing patient symptom frequencies and symptoms described as most bothersome. *Other symptoms reported included headaches or migraines, skin reactions, loss of weight, coughing and shortness of breath, sleep disturbances and insomnia, numbness in hands and fingers or neuropathy, confusion, renal insufficiency, localized weakness, bone lesions, visual impairment or strabismus, and nausea. Table 2. Qualitative results: findings and key quotes from study participants. Domain Findings Key quotes* Roadmap to diagnosis Most patients were diagnosed by chance, especially in the USA “It was just during a regular check-up … ” “Yeah, it was a routine blood test, and I went to my family physician and something seemed a little irregular on the bloodwork.” “I actually just went in for a physical … ” Reactions to diagnosis of SMM Patients felt shocked, unsettled, confused or frightened, or in denial With time and understanding of the condition (having SMM not necessarily means progression to MM), some experienced acceptance “ … the whole thing was kind of a shock … ” “Actually, you’re like in the fog.” “It was a blow, I must say. It is cancer after all. It’s not anodyne. Although the hematologist I saw back then was very reassuring and said ‘It doesn’t mean that it will activate. But yes, it’s unlucky for you that we find it now because it will spoil your life for some time.’ And then, that’s it … It does easily take a year to accept this thing, and then that’s it, we live with it.” Disease awareness Many patients were unaware of the term “high-risk SMM” “When they use these terminologies in the hospital, in the hematology and oncology wards, you already understand that it is a type of tumor. They told me about smoldering and explained to me what myeloma was. I don’t know if statistically it always turns into myeloma or if there is a percentage that remains smoldering. I saw a black tunnel and realized it was a blood cancer.” “Well, the words ‘high risk’ were never mentioned but … ” “It’s the first time I’ve heard what you just told me (ie, term ‘high-risk smouldering multiple myeloma’) … It doesn’t ring any bell at all … I don’t understand medical stuff, that’s why, maybe I heard it but I didn’t pay attention.” Disease experience: signs and symptoms Fatigue and pain were the most frequent and most important symptoms affecting patients Symptoms were more frequently reported by participants with MM vs SMM “Well, they went from extreme tiredness to…” “ … Fatigue, especially fatigue, not so much weakness, more fatigue.” “ … so for the moment the disease remains indolent, apart from a few symptoms, such as chronic tiredness. Because of this I’ve had to change my habits a bit, for example sometimes I work from home. I also have had a lot of bone and muscle pain, that made me not sleep well at night, that’s why I went deeper to find out what it was about.” “Well. The pain … the pain, I mean … my back hurts … ” “ … .But before that, I had never experienced violent pain like this … ” Disease experience: impact on life The psychological impact of the disease was the most prevalent and most important impact in participants’ lives Impacts on day-to-day life were slightly more frequently reported by participants with MM vs SMM Physical and cognitive impacts either appeared until the disease had progressed to MM or changed when progressing if present at an earlier stage “I do experience anxiety and worry, of course. You know, when your mind gets to wander and think, of course I have fear. What could this turn into? What could happen next? You never know.” “ … I wouldn’t say that I have no social life, because I have my job, but in the afternoon, all I do is rest. … Something that I didn’t do at all before.” “Well, um, a little more additional stress in my life, which was already stressful, I won’t deny that [laughs], a little more stress and anxiety, yes, of course.” “You don’t know what’s going to happen in the future, … it’s my children, that’s the thing, yes … I’d like to be with my children, in good health.” “Negative things that … not that much. I try to be positive, but of course I don’t trust this life that much anymore because it is possible that there is a sickness … you don’t know what’s going on next month or next day in your life, so I’m not that 100% positive like before, but I try to push myself.” “I would say it affected the social area the most … I mean, everything is connected to it, also the economical aspect.” Experience with SMM treatment 70% of patients accepted their clinicians’ recommendations and understood no treatment was available or recommended at that time Patients relied heavily on physician recommendations for treatment “ … for SMM … No, there is no treatment, just observation … until it progresses to MM.” “No, no. I have never heard of treatment in the SMM phase.” “It’s a yes for MM, nothing for SMM.” “They told me that it is monitoring. I had two physicians over the 6 years. They both told me the same thing: ‘You should get proper follow-up, especially since you are a young patient. So, your health status may deteriorate very fast.’” “No, not really. I’m not one to get information from the internet for … [laughs] … But no, they already told me there is really nothing, so I haven’t really looked or anything.” Willingness to undergo treatment Patients’ willingness to undergo treatment depended on: Possible outcomes (47%) If endorsed by clinician (24%) Reduced risk of side effects or chemical effects (13%) The evidence behind the treatment (5%) Type of treatment (3%) No specific reason (5%) “… If a treatment had been available that would have prevented the progression of the disease in my SMM, then I would have done it.” “I would have let myself be guided by the doctor, I mean, you’re in your doctor’s hands. And you have to trust him or not … So … depending on the data, I would have asked a lot of questions and … ” “That it doesn’t have too many side effects.” “It all depends on the treatment. If it’s a light treatment, yes, but if it’s a heavy treatment, before I figure out what is going to happen to me, I wouldn’t have accepted. I would have waited.” “ … but yes, if I had known it to be useful, yes, I think so.” “ … I mean if I’m going to be progressing then I should probably just get on the cancer treatment that they’ve got to really be proactive.” Treatment expectations Delaying disease progression to MM was important to patients Some expected a full cure from disease Some found all outcomes important “Well, the outcomes would be to keep the disease from progressing for an indefinite amount of time and what would the benefits be of doing that treatment versus let’s say, the side effects if there were any?” “The total remission of it. I mean, when I had the autologous transplant done … That in the following tests, they would say: ‘Hey, look, your condition has completely subsided’ … That would be the greatest victory. Of course.” “Definitely to improve symptoms. Maybe hopefully that the disease could go away.” “Um, I don’t know, all those are important, really. I couldn’t put one first. All those, for me, all those are equally important.” PFS thresholding exercise: most important attribute PFS and side effects were equally important “Well then … side effects are not so problematic to me. I know it’s hard, but well … And as for the time, obviously, it’s long. 6 years is a long time.” “For me, it’s to get treated, to stop it there. 70 months, … ” “Eh the side effects, which then may disappear even with further treatment. My experience (with treatments) tells me that it was good what I did, so not having done smoldering therapies.” “The first thing I looked at was the problem. So, it causes side effects and even though it’s not the 100 figures, it still is a possibility. I don’t want to have that chance and what the focus is on is the progression to multiple myeloma.” PFS thresholding exercise: least important attribute Treatment mode of administration was the least important “The frequency of the injections. You know it’s no big deal if you agree to do something, you just do it and get through it.” Yes, but this (side effects) is absolutely not a problem to me, because I went through so much in my life with this, that I have no problem with that.” *Quotes were from different patients. Abbreviations: MM: multiple myeloma; PFS: progression-free survival; SMM: smoldering MM.
Table 2.
Qualitative results: findings and key quotes from study participants.
*Quotes were from different patients. Abbreviations: MM: multiple myeloma; PFS: progression-free survival; SMM: smoldering MM.
| Domain | Findings | Key quotes* |
| Roadmap to diagnosis | Most patients were diagnosed by chance, especially in the USA | “It was just during a regular check-up … ” “Yeah, it was a routine blood test, and I went to my family physician and something seemed a little irregular on the bloodwork.” “I actually just went in for a physical … ” |
| Reactions to diagnosis of SMM | Patients felt shocked, unsettled, confused or frightened, or in denial With time and understanding of the condition (having SMM not necessarily means progression to MM), some experienced acceptance | “ … the whole thing was kind of a shock … ” “Actually, you’re like in the fog.” “It was a blow, I must say. It is cancer after all. It’s not anodyne. Although the hematologist I saw back then was very reassuring and said ‘It doesn’t mean that it will activate. But yes, it’s unlucky for you that we find it now because it will spoil your life for some time.’ And then, that’s it … It does easily take a year to accept this thing, and then that’s it, we live with it.” |
| Disease awareness | Many patients were unaware of the term “high-risk SMM” | “When they use these terminologies in the hospital, in the hematology and oncology wards, you already understand that it is a type of tumor. They told me about smoldering and explained to me what myeloma was. I don’t know if statistically it always turns into myeloma or if there is a percentage that remains smoldering. I saw a black tunnel and realized it was a blood cancer.” “Well, the words ‘high risk’ were never mentioned but … ” “It’s the first time I’ve heard what you just told me (ie, term ‘high-risk smouldering multiple myeloma’) … It doesn’t ring any bell at all … I don’t understand medical stuff, that’s why, maybe I heard it but I didn’t pay attention.” |
| Disease experience: signs and symptoms | Fatigue and pain were the most frequent and most important symptoms affecting patients Symptoms were more frequently reported by participants with MM vs SMM | “Well, they went from extreme tiredness to…” “ … Fatigue, especially fatigue, not so much weakness, more fatigue.” “ … so for the moment the disease remains indolent, apart from a few symptoms, such as chronic tiredness. Because of this I’ve had to change my habits a bit, for example sometimes I work from home. I also have had a lot of bone and muscle pain, that made me not sleep well at night, that’s why I went deeper to find out what it was about.” “Well. The pain … the pain, I mean … my back hurts … ” “ … .But before that, I had never experienced violent pain like this … ” |
| Disease experience: impact on life | The psychological impact of the disease was the most prevalent and most important impact in participants’ lives Impacts on day-to-day life were slightly more frequently reported by participants with MM vs SMM Physical and cognitive impacts either appeared until the disease had progressed to MM or changed when progressing if present at an earlier stage | “I do experience anxiety and worry, of course. You know, when your mind gets to wander and think, of course I have fear. What could this turn into? What could happen next? You never know.” “ … I wouldn’t say that I have no social life, because I have my job, but in the afternoon, all I do is rest. … Something that I didn’t do at all before.” “Well, um, a little more additional stress in my life, which was already stressful, I won’t deny that [laughs], a little more stress and anxiety, yes, of course.” “You don’t know what’s going to happen in the future, … it’s my children, that’s the thing, yes … I’d like to be with my children, in good health.” “Negative things that … not that much. I try to be positive, but of course I don’t trust this life that much anymore because it is possible that there is a sickness … you don’t know what’s going on next month or next day in your life, so I’m not that 100% positive like before, but I try to push myself.” “I would say it affected the social area the most … I mean, everything is connected to it, also the economical aspect.” |
| Experience with SMM treatment | 70% of patients accepted their clinicians’ recommendations and understood no treatment was available or recommended at that time Patients relied heavily on physician recommendations for treatment | “ … for SMM … No, there is no treatment, just observation … until it progresses to MM.” “No, no. I have never heard of treatment in the SMM phase.” “It’s a yes for MM, nothing for SMM.” “They told me that it is monitoring. I had two physicians over the 6 years. They both told me the same thing: ‘You should get proper follow-up, especially since you are a young patient. So, your health status may deteriorate very fast.’” “No, not really. I’m not one to get information from the internet for … [laughs] … But no, they already told me there is really nothing, so I haven’t really looked or anything.” |
| Willingness to undergo treatment | Patients’ willingness to undergo treatment depended on: Possible outcomes (47%) If endorsed by clinician (24%) Reduced risk of side effects or chemical effects (13%) The evidence behind the treatment (5%) Type of treatment (3%) No specific reason (5%) | “… If a treatment had been available that would have prevented the progression of the disease in my SMM, then I would have done it.” “I would have let myself be guided by the doctor, I mean, you’re in your doctor’s hands. And you have to trust him or not … So … depending on the data, I would have asked a lot of questions and … ” “That it doesn’t have too many side effects.” “It all depends on the treatment. If it’s a light treatment, yes, but if it’s a heavy treatment, before I figure out what is going to happen to me, I wouldn’t have accepted. I would have waited.” “ … but yes, if I had known it to be useful, yes, I think so.” “ … I mean if I’m going to be progressing then I should probably just get on the cancer treatment that they’ve got to really be proactive.” |
| Treatment expectations | Delaying disease progression to MM was important to patients Some expected a full cure from disease Some found all outcomes important | “Well, the outcomes would be to keep the disease from progressing for an indefinite amount of time and what would the benefits be of doing that treatment versus let’s say, the side effects if there were any?” “The total remission of it. I mean, when I had the autologous transplant done … That in the following tests, they would say: ‘Hey, look, your condition has completely subsided’ … That would be the greatest victory. Of course.” “Definitely to improve symptoms. Maybe hopefully that the disease could go away.” “Um, I don’t know, all those are important, really. I couldn’t put one first. All those, for me, all those are equally important.” |
| PFS thresholding exercise: most important attribute | PFS and side effects were equally important | “Well then … side effects are not so problematic to me. I know it’s hard, but well … And as for the time, obviously, it’s long. 6 years is a long time.” “For me, it’s to get treated, to stop it there. 70 months, … ” “Eh the side effects, which then may disappear even with further treatment. My experience (with treatments) tells me that it was good what I did, so not having done smoldering therapies.” “The first thing I looked at was the problem. So, it causes side effects and even though it’s not the 100 figures, it still is a possibility. I don’t want to have that chance and what the focus is on is the progression to multiple myeloma.” |
| PFS thresholding exercise: least important attribute | Treatment mode of administration was the least important | “The frequency of the injections. You know it’s no big deal if you agree to do something, you just do it and get through it.” Yes, but this (side effects) is absolutely not a problem to me, because I went through so much in my life with this, that I have no problem with that.” |
Tiredness/fatigue (88% vs 48%), weakness (52% vs 20%), loss of appetite (24% vs 8%), loss of balance (20% vs 4%), and constipation (20% vs 0%) were more common in patients with MM than with HR-SMM (Supplemental Figure S4). Overall symptom burden rates were substantially lower in HR-SMM, with 32% ( n = 8/25) of HR-SMM patients fully asymptomatic, which is consistent with published evidence of non-CRAB symptom burden in SMM [ 32 , 33 ]. For patients with MM, symptoms such as pain, fatigue, or weakness could have been present during the SMM phase before progressing to MM, but patients reported an increase in the severity of these symptoms that accompanied progression to MM.
Impact of HR-SMM and MM on health-related quality of life
Overall, the psychological impact (46/50, 92%) of the disease and the impact on perspectives for the future (41/50, 82%) were the most prevalent, even for asymptomatic patients ( Figure 2 ). Forty‑two percent of patients (21/50) considered the psychological impact the most important, and anxiety, worry, and fear were the most common descriptors used. From a qualitative perspective, patients described their reactions to the initial diagnosis as feeling shocked, unsettled, confused, frightened, or in denial. Some patients felt calmer after understanding that a diagnosis of SMM did not necessarily mean progression to MM (patient quotes in Table 2 ). Some patients reported that the diagnosis increased bonding with family members or gave them a new appreciation for life. Figure 2. Impact of high-risk SMM and MM on life overall. Horizontal bar graph showing patient reported impacts and most important impacts across life domains. Abbreviations: MM: multiple myeloma; SMM: smoldering MM.
All patients in the MM group and 84% (21/25) in the HR-SMM group reported a psychological impact of their diagnosis. Self-reported impacts on day-to-day life were more frequently reported by patients with MM compared with HR-SMM; for instance, the increments in rates were 40% (96% vs 56%) for physical impact, 36% (84% vs 48%) for impact on work, 36% (100% vs 64%) for impact on future perspectives or planning, and 32% (76% vs 44%) for impact on social interactions, respectively (Supplemental Figure S5A).
Patients in the MM group were asked about health-related quality of life (HRQoL) impacts they experienced during the HR-SMM phase versus being diagnosed with MM. The self-reported psychological impact and impact on family, social interactions, or relationships were more prominent at the HR-SMM stage. Impacts on future planning and perspectives, physical function, and daily life activities were those most affected by disease progression (Supplemental Figure S5). All patients reported worsening physical and cognitive impacts with disease progression. Supplemental Table S3 shows EORTC-QLQ-C30 functional scales results.
Treatment experience and expectations
Patients preferred to know the treatment benefits and to be reassured of a low side-effect risk ( Table 2 ). Most patients would rely on clinician advice to make treatment decisions. Of the treatment-naïve patients, 70% were not treated because the physician recommended that treatment was not needed, burdensome, or not available. Only three patients spontaneously mentioned an independent search for treatment information.
A list of potential treatment outcomes was presented to all patients to be ranked by importance. These attributes were presented as items for patients to prioritize according to their personal values, with no claims or implications that any treatment possessed these attributes. Forty-six patients completed the ranking, although 21 (21/50, 42%) felt it was complicated, and 4 (4/50, 8%) were unable to complete the task. Increasing life expectancy and symptom improvement were the 2 most often ranked attributes. “Delay disease progression to MM” was ranked as the most important (14/46, 30%), followed by “increase life expectancy” (11/46, 24%); whereas “improvement of symptoms” (12/46, 26%) and “reduce the impact of SMM in life” (9/46, 20%) were more commonly ranked in the third position or lower (Supplemental Table S4). Overall, 11 patients (11/50, 22%) mentioned spontaneously that they expected a treatment that would offer to “cure” the disease.
Treatment preferences – findings of the thresholding exercise
At the first-choice task to select treatment or no treatment (the treatment option included 3 years of varying frequency of subcutaneous injections with a 70-month PFS and a 42% risk of AEs; the no-treatment option involved a 38-month PFS with active monitoring), 31 patients (31/50, 62%) chose to have treatment. Of these, 23 patients (23/31, 74%) provided a clear reason for choosing to have treatment. The most common reason was trust in the medication (perceived as a “cure,” n = 10), followed by a clear description of benefits outweighing the risks (and administration requirements, n = 6), and third by the improvement in PFS (compared with active monitoring, n = 4). Three patients expressed hesitation when choosing to have treatment, and they would require additional information/evidence supporting the treatment or clinician endorsement. For those choosing not to have treatment, 17 patients (17/19, 90%) provided a clear reason, with “not enough benefit” being the most common ( n = 7) followed by the fear of side effects ( n = 6); other reasons included the treatment option being unrealistic, needing clinician endorsement, preference for just monitoring, or fear of injections ( Table 2 ).
Overall, the median acceptable min-PFS benefit (minimum acceptable benefit [MAB]; range, 39–100 months) for treatment burden and adverse effects was 60 months (interquartile range [IQR]: 42–99 months). The MAB was similar for the HR-SMM group ( n = 25; MAB [IQR]: 61 [45–100] months) and the MM group (n = 25; MAB [IQR]: 59 [41–87] months). Heterogeneity in MAB was found in both MM and HR-SMM groups as PFS >100 months (12/50, 24%), PFS 40 to 50 months (12/50, 24%), and PFS <40 months (8/50, 16%) were the 3 most common MAB ranges. Of the 12 patients who selected the highest PFS range (>100 months), 75% ( n = 9) had HR-SMM. For those who selected the lowest PFS range (<40 months), 3 had HR-SMM and 5 had MM. The HR-SMM group had a higher proportion of patients selecting extreme MAB ranges, whereas the MM group had a more even distribution (Supplemental Figure S6).
Of the attributes presented in this exercise (PFS, side effects, mode of administration), the most important attribute influencing patient choice was PFS or side effects (17/41, 41%, equally important). Mode of administration was most important for five patients (owing to a fear of needles, perceiving struggles with the frequency, or taking medication as reminders of being unwell) and least important for eight patients. Some patients considered all attributes important.
Thirty-eight patients (HR-SMM, n = 18; MM, n = 20) were asked whether they would be, or would have been (in the case of patients with MM), willing to be treated during the HR-SMM stage or would prefer (or would have preferred) to wait until disease progression. Twenty-three patients (23/38, 61%) were willing to start treatment, 19 of whom (19/23, 83%) had an MAB ≤70 months (range: <40 to >100 months with a 2-month precision); 5 mentioned certain conditions, for example only with clinician endorsement or only with ensured treatment benefit. Twelve patients (12/38, 32%) would prefer to wait. For patients who could not decide (2/38, 5%) or would depend on clinician advice (1/38, 3%), the MAB was 50 to 70 months ( Figure 3 ). Figure 3. Willingness to receive treatment during the high-risk SMM stage. Consists of 38 patients from the high-risk SMM and MM groups. Bar graph showing willingness to start treatment by minimum acceptable progression free survival months. Of the total population of 50 patients, 6 (12%) had received treatment ( n = 2, high-risk SMM; n = 4, MM). *Including 1 patient who would start treatment following the recommendation of their physicians. Abbreviations: MM: multiple myeloma; PFS: progression-free survival; SMM: smoldering MM.
Discussion
The findings of this mixed-methods study informed our understanding of disease awareness in patients with HR-SMM and MM that progressed from HR-SMM, as well as the psychological impacts the diagnosis had on their lives, their preferences for potential treatments, and the MAB required to accept treatment administration and associated adverse effects.
On the basis of the targeted literature review and our knowledge of the disease and treatment landscape of HR-SMM and MM, we derived three hypotheses focusing on patient views of HR-SMM disease progression, awareness of treatment options, and treatment preferences.
The study results showed that individuals diagnosed with HR-SMM are concerned about disease progression. Anxiety, worry, and fear were the most common terms patients used—also used by patients with SMM [ 25 ]—when describing the psychological impacts of HR-SMM, even among those who were asymptomatic. Psychological impacts were prevalent both before and after progression to MM.
The study also examined whether individuals with HR-SMM or MM that progressed from HR-SMM prefer treatment during the SMM stage of disease versus no treatment, and a willingness to tolerate adverse effects if the treatment delays disease progression to MM. There was strong evidence from the PFS thresholding task that patients in both groups were willing to tolerate adverse effects if the treatment delayed disease progression to MM. Patients required a median PFS of 60 months (IQR, 42–99 months) to accept a treatment with a 42% risk of adverse effects and requiring a subcutaneous injection. Although similar overall, preferences differed slightly between HR-SMM and MM groups; of those requiring the highest possible MAB (≥100 months), 75% of patients (9/12) were in the HR-SMM group. In ranking exercises, adverse effects were ranked as more important by patients with HR-SMM than those with MM, which may be due to the asymptomatic nature of HR-SMM. Patients with HR-SMM and MM desired a treatment to cure their disease regardless, in part owing to the psychological impact of the disease.
A priori, we hypothesized that individuals diagnosed with HR-SMM may be less aware of treatment options compared with individuals with MM. We found that levels of treatment awareness were low for the entire study population, and there was no evidence that this varied by HR-SMM or MM status. Of the total sample of 50 patients, 6 reported receiving treatment during the HR-SMM phase of their disease: 4 from the MM group and 2 from the HR-SMM group. However, details about how these patients received their treatment (for example, whether by participating in clinical trials or by off-label prescriptions) were not clear—being part of a clinical trial was an exclusion criterion, and participants were not asked about off-label use of treatment during interviews. Examination of the qualitative data provided no indication of a difference in awareness about treatment options; both groups reported being unaware of treatment options for HR-SMM and relying almost exclusively on clinician recommendations to monitor their health until indications of progression.
Patients included in the current study expressed their concerns and worries about disease progression. Evidence from real-world data demonstrated that most patients with HR-SMM progress to MM; however, a much smaller proportion of patients progressed to MM in those who received treatment shortly after HR-SMM diagnosis compared with those who were actively monitored (11% [2/19] vs 72% [51/71]) [ 39 ]. Most recently, the benefit of early intervention for HR-SMM, such as a significantly lower risk of disease progression compared with active monitoring, has been further demonstrated in the phase II I-PRISM trial [ 40 ] and the phase III AQUILA trial. These encouraging findings suggest an opportunity for patients to achieve their goals of delayed progression. The first treatment for HR-SMM, daratumumab, received approval by the European Commission in July 2025 [ 14 ].
Many patients expressed a willingness to accept treatment at the HR-SMM stage in the interviews. The thresholding exercise, which elicited individual-level trade-offs between risk, treatment benefit, and convenience attributes, showed that patients would accept the treatment burden (risk of adverse effects and repetitive treatment administration) with a minimal acceptable PFS of 60 months, which aligns with the findings of the AQUILA trial (ie, PFS was 63% with daratumumab and 41% with active monitoring at 60 months in patients with HR-SMM). In AQUILA, patients treated with daratumumab demonstrated a 51% reduction in risk of disease progression/death versus the active monitoring arm (hazard ratio [HR]: 0.49; 95% confidence interval [CI], 0.36–0.67) in the overall ITT population [ 41 ]. This risk reduction was even more pronounced in patients classified as being at high risk of disease progression according to Mayo 2018 risk criteria [ 36 ], with a 64% reduction in risk (HR: 0.36, 95% CI 0.23–0.58) compared with active monitoring [ 41 ]. In a UK survey of patients with SMM or monoclonal gammopathy of undetermined significance, patients desired treatments to prevent progression to MM rather than curative treatments after the disease had become active [ 42 ]. Furthermore, patients noted that treating SMM may contribute to reduced anxiety related to disease progression and may lead to improved quality of life and increased life expectancy. Given most patients with HR-SMM rely on their physicians to decide whether to initiate treatment, shared decision-making and patient education on available options in light of new advances (eg, using daratumumab for HR-SMM) are warranted.
Strengths and limitations
Findings from the current study supplement the data in the existing literature, which has not explored the perceptions and preferences of patients with SMM. We included patients with HR-SMM diagnosed per IMWG or Mayo Clinic risk stratification criteria [ 35 , 36 ], which were commonly used at study initiation prior to the newly developed Precursor Asymptomatic Neoplasms by Group Effort Analysis (PANGEA) criteria [ 43 ]. However, insights from the current study amplify the voice of patients with HR-SMM, a previously under-reached population, regarding potential SMM treatments. More broadly, the findings of this study align with those of existing studies, which found that patients hope for treatments that extend life with prolonged progression-free intervals, minimal cancer symptoms, and tolerable adverse effects [ 16–18 , 32–34 ].
The study has several limitations. First, although stated preference tools, including thresholding tasks, are a common method for eliciting stakeholder preferences for a wide range of products and services [ 44 , 45 ], the degree to which reported preferences reflect actual preferences remains uncertain [ 44 , 46 , 47 ]. Some stated preference tools may have utility in predicting real-world choices [ 44 ], but there is less evidence on thresholding tasks specifically. As with all stated preference tasks, the results must be interpreted within the context of the set of attributes and levels included in the study design. For example, the results of the current study can interpret the minimum acceptable benefit only for the 42% adverse effect risk presented in the task. It is worth noting that this risk was the most conservative estimate based on a specific symptom reported from a trial [ 11 ], whereas patients in real-world settings may have different considerations depending on the symptoms as well as physical and/or psychological experiences that are most meaningful to each person. In addition, adverse effect was a composite measure; different people weighed each component differently, which introduced noise to the results. A more flexible tool for quantitative-preference elicitation, such as a discrete-choice experiment or multidimensional thresholding tool, would facilitate estimation of trade-offs across attributes, though it would require a larger sample size than that obtainable in this study.
Moreover, qualitative methods have unique limitations. For example, acceptability biases may impact responses, a main idea may dominate the conversation, or information may be missed if not all questions are covered or given equal attention by interviews. Further, in mixed-methods studies such as this, concepts measured may be subtly different between methods used. The sampling frame sought to achieve heterogeneity in perspectives across disease stages and countries, and this intention for variety of perspective means generalizability may be difficult, especially given that a high proportion of patients were educated beyond high school. Furthermore, approximately 40% of participants were aged ≤50 years, which may not reflect the older age profile typical of real-world SMM populations [ 5 , 8 ], partly attributable to recruitment via social media and patient networks that inherently favor younger patients. The perceptions and treatment preferences of older patients with different comorbidity profiles and treatment priorities may therefore be underrepresented, and caution should be exercised when extrapolating findings to this group. The higher proportion of patients with HR-SMM with an ECOG score >0 versus patients with MM may also indicate a potential selection bias. Because only the functional scales of the EORTC-QLQ-C30 were administered, this precluded full standardized domain scoring and limits direct comparison with studies reporting complete instrument data. Finally, small sample sizes precluded country-level analysis of symptoms, disease impacts, and treatment preferences, and regional differences in patient perceptions may exist. Symptom data were collected via open-ended patient report and are not equivalent to clinician-assessed CRAB criteria; some symptom attribution by patients with HR-SMM may reflect comorbidities or general health rather than SMM itself. Notably, diagnostic pathways differed between the USA and Europe, where all US patients (100%) received their SMM diagnosis incidentally while asymptomatic compared with 47% of European patients, and treatment availability varied by country. Future studies with larger, country-stratified samples are needed to examine these differences systematically.
Conclusion
Patients highlighted the considerable psychological as well as physical and functional burden imposed by the potential for progression from HR-SMM to MM. Additionally, patients were willing to hear about potential treatment options from their clinicians and benefit from shared decision-making regarding their care. Furthermore, this study demonstrates a willingness among patients with HR-SMM and MM to tolerate the adverse effects and scheduled administration of SMM treatments in exchange for a delay in progression to MM.
Supplementary Material
Supplemental Material
Quaife_SMM Pt Preference_Future Oncology_Suppl_7July2026.docx
Quaife_SMM Pt Preference_Future Oncology_Suppl Tables_11Jun2026.docx
Acknowledgments
This research was presented at the International Society for Pharmacoeconomics and Outcomes Research Conference, May 5–8, 2024, Atlanta, GA.
Article highlights
The psychological impact, particularly anxiety, worry, and fear, associated with smoldering multiple myeloma was the most commonly cited factor that affected health-related quality of life, even for patients who were asymptomatic. Delaying disease progression to multiple myeloma was ranked as the most important treatment attribute by 30% of patients, whereas 22% mentioned they would expect to be fully “cured” if treated. The average minimum acceptable duration of progression-free survival in exchange for treatment burden and adverse effects was 60 months. Patients with high-risk smoldering multiple myeloma, as well as those whose disease had progressed to multiple myeloma, expressed the need for more information about smoldering multiple myeloma treatment options, education about treatment from their clinicians, a low level of adverse effect risk, and certainty in treatment benefit.
Disclosure statement
Matthew Quaife and Cecilia Jimenez-Moreno were employees of Evidera at the time of the study. Blanca Gros Otero, Aisha Asra, Niodita Gupta-Werner, Katharine S Gries, Marie-Kristin Leisten, Kathryn Matt, Robin Carson, Robyn Dennis, Jianming He, Bennett Levitan, and Sacheeta Bathija are employees and shareholders in Johnson & Johnson.
The authors have no other relevant affiliations or financial involvement, with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, apart from those disclosed.
Medical writing support was provided by Shuang Li, PhD, CMPP, of Eloquent, part of Envision Ignite, an Envision Medical Communications agency, a part of Envision Pharma Group, and funded by Johnson & Johnson.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Ethical declaration
The protocol was approved by a central institutional review board in the US (Salus, Ethics & Inclusion Study Number 22116-01, approved on 14 June 2022). This type of research, characterized by recruitment outside clinical settings, qualifies as low-risk market research and was determined eligible for ethics exemption for the multi-country submission, covering all four participating countries.
Following confirmation of diagnosis, subjects were provided with the web link for an electronic consent form, and researchers and participants agreed on a date and time for the interview. The electronic consent form was approved by Salus IRB (No. 22116IFON_A_2710562-01A to -02) and informed the participant about the requirements, risks, and expectations from their participation as well as the data collection, data privacy, and storage procedures to protect anonymity and ensure data protection following GDPR and HIPAA standards or legal data protection requirements. Voluntary consent from participants was documented and all legal data protection requirements were followed. Participants were able to print a PDF version of the consent, giving them enough time to read and consider the study specifics. Consent to take part in the audio-recorded interview was also confirmed verbally at the start of each interview.
Data availability statement
The data sharing policy of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency . As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu .
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14796694.2026.2710562
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