NEW YORK – Researchers in Iceland have initiated a population-based study to improve understanding of the biology of a preclinical form of multiple myeloma, identify factors associated with progression to full-blown disease, and determine the optimal clinical management of these at-risk patients.
The ongoing study, a detailed description of which was published Monday in Blood Cancer Journal, has enrolled 80,759 people across Iceland, comprising over 54 percent of individuals in the country born before 1976. Dubbed "Iceland Screens, Treats, or Prevents Multiple Myeloma," or iStopMM, the study started in 2016, aiming to enroll 70,000 Icelanders over age 40, and is designed to assess the benefits and potential harms of population-based screening for monoclonal gammopathy of undetermined significance, or MGUS, a precursor to multiple myeloma characterized by the presence of an abnormal protein, called M protein, or an abnormal ratio of free immunoglobulin light chains in the blood.
Participants who are found to have MGUS are randomized to one of three study arms: one in which no further action is taken, and the person continues receiving conventional healthcare as though they had never been found to have MGUS; one in which patients undergo current guideline-recommended follow-up procedures for MGUS; and one in which they undergo a more intensive follow-up regimen.
The primary aim of iStopMM is to assess the overall survival among patients assigned to each arm after five years. Specifically, investigators will compare overall survival in arms two and three combined versus overall survival in arm one. Additional study endpoints include cause-specific survival due to multiple myeloma or other lymphoproliferative disorders; patients' psychiatric health and wellbeing; and the cost-effectiveness of the screening.
The study also includes a massive biobanking effort, through which all of the data from the study are collected and cross-linked with existing Icelandic registries, such as the Icelandic Cancer Registry, the Icelandic Causes of Death Registry, the Icelandic Prescription Medicines Registry, and the Icelandic Hospital Discharge Registry, among other datasets.
Researchers at the Binding Site laboratory in Birmingham, UK, are analyzing collected samples using capillary zone electrophoresis for M protein and for free light chains, immunoglobulins, and total protein. So far, the lab has returned more than 600,000 data points.
"The iStopMM study's extensive biobanking is enabling genetic and immune testing," Brian Durie of the International Myeloma Foundation, who is an investigator in iStopMM, said in a statement. "Longer-term follow-up will not only yield groundbreaking data about the biology of early disease and the value of early diagnosis, but also shed light on the optimal interventions to achieve both prevention and a cure."
Interim analyses within iStopMM are planned when 500 people with MGUS have been followed for six months; when 100 people with MGUS have died; and when people with MGUS randomized to one of the monitoring arms have been followed for five years. If at any one of these interim analyses there is a significant overall survival discrepancy between arm one and arms two and three, the investigators plan to unblind arm one, in which patients are not receiving any additional care, and offer those patients a choice between randomization to arms two or three or regular clinical follow-up.
"Understanding the epidemiologic, genetic, and immunologic factors that go along with an increased risk of myeloma's progression could open the door to early intervention efforts in high-risk patients and possible preventive strategies," Sigurdur Kristinsson of the University of Iceland, who is the study's lead author, said in a statement. "This would improve overall survival and quality of life for patients worldwide."
The study is funded by the International Myeloma Foundation, and according to IMF, is now the clinical trial with the largest single-country participation rate. The study authors cited several aspects of the trial protocol that have contributed to this high participation rate, including allowing patients to complete the consent process online or by mail and collecting blood samples for research while patients are already having blood drawn for routine care. The use of social media and traditional media campaigns also helped spread the word about the study among Icelanders, the authors said.