Table 5 Application of the Wilson and Jungner criteria and the additional recently proposed emerging criteria to multiple myeloma.

The condition sought should be an important health problem

Yes

MM is the second most common hematological malignancy with 31,810 new cases and 12,770 attributed deaths in 2018 in the United States alone⁵³

There should be an accepted treatment with recognized disease

Yes

Treatment for MM is widely available and international organizations recommending specific care for MM⁵⁴

Facilities for diagnosis and treatment should be available

Yes

This at least applies to developed countries

There should be a recognizable or early symptomatic stage

Yes

MGUS and SMM are clearly established entities¹ and precede all cases of MM^5,6

There should be a suitable test or examination

Yes

SPEP, IFE, and FLC assays are sensitive and specific tests for MM and its precursors and can easily be repeated to confirm the diagnosis⁵⁵

The test should be acceptable to the population

Yes

Screening is done by a blood test which is widely acceptable

The natural history of the condition, including development from latent to declared disease, should be adequately understood

Yes

Although there is still much to learn about the underlying pathogenesis of MM, a wealth of literature on the subject exists⁵⁶. Furthermore, the natural history of MM and its development from precursor disorders is adequately understood with studies including decades of follow-up available⁵⁷

There should be an agreed policy on whom to treat as patients

Yes

Although this is currently a moving target, there are clear guidelines on whom to treat, i.e., those with end-organ damage or myeloma defining events. In light of recent evidence, however, treatment might become available at even earlier stages^20,21,58. If and when such early treatment is appropriate, there are institutions in place that will include such treatment in their guidelines

The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditures on medical care as a whole

Unknown

There are currently no screening studies available for MM and its precursor conditions and a cost-benefit analysis is not available. This will be addressed as part of the iStopMM study

Case finding should be a continuing process and not a “once and for all” project

Yes

Since blood sampling for screening can be carried out at any time MM screening can be a continuing process

The screening program should respond to a recognized need

Yes

Although survival in MM has dramatically improved in recent years^17,18,19 the disease remains a major burden on affected individuals and healthcare systems⁵⁹

The objectives of screening should be defined at the outset

Yes

The objectives of screening for MM are clear: providing earlier treatment for MM

There should be a defined target population

Unknown

Currently, a well-defined target population for screening does not exist. This is addressed with regards to age, sex, and various other measures in the iStopMM study. However, due to the dominant white ethnicity of the Icelandic population, race cannot be addressed in the iStopMM study. Another study, the PROMISE study, focuses on the impact of screening in individuals of African descent. (ClinicalTrials.gov Identifier: NCT03689595)

There should be scientific evidence of screening program effectiveness

Unknown

The objective of the iStopMM study is to provide this evidence

The program should integrate education, testing, clinical services, and program management

Yes

There are excellent patent resources available in MM and its precursor disorders. Any screening program would be able to fulfill this criterion

There should be quality assurance, with mechanisms to minimize potential risks of screening

Yes

This organizational issue can be solved in MM screening since there are clear response criteria⁶⁰ and accepted relevant endpoints like survival available for MM

The program should ensure informed choice, confidentiality, and respect for autonomy

Yes

This is a practical issue that does not require scientific proof of concept, although such proof is provided in the iStopMM trial

The program should promote equity and access to screening for the entire population

Yes

Since the cost of MM screening is relatively low and requires no specialized equipment at the point of patient care, equity in testing is therefore feasible. Follow-up for precursor disorders and treatment for MM can however be expensive and could lead to inequity in non-universal healthcare systems

Program evaluation should be planned from the outset

Yes

The practical issue of evaluation is possible for MM as proven by the methodology described above

The overall benefits of screening should outweigh the harm

Unknown

This is the principal study objective of the iStopMM study