MM Therapy Attrition Not as High as Previously Reported

A new report upends the conventional wisdom around the reportedly high attrition rate among patients with multiple myeloma (MM) after their initial therapy.

The report, based on a database of Canadian patients, found attrition rates were lower than previously reported and that the most common contributor to attrition was death. The study was published in Blood Cancer Journal.

Previous studies have suggested that only 50% of 61% of patients with MM go on to receive second-line therapy, explained the study authors from Ottawa Hospital Research Institute. Rates of treatment continuation decrease further with each subsequent relapse, they added. However, the authors said truly understanding attrition can be difficult, because there can be many different reasons patients do not go on to receive further therapy. For instance, studies based on administrative claims databases likely overestimate attrition, they said, because there is often an inability to capture reasons for apparent attrition other than death.

“The most important of these include patients treated with planned fixed-duration initial therapy who remain in remission or those undergoing continuous first-line therapy who have maintained their response,” they wrote.

Randomized controlled trials (RCTs) also have suggested high rates of attrition, the authors said.

“Unfortunately, these RCTs did not report subsequent therapies line-by-line, and so further clarity on how many patients ultimately received third- or fourth-line therapy and beyond is not possible with this dataset,” they wrote.

In hopes of generating a more accurate understanding of attrition among people with MM, the authors utilized the Canadian Myeloma Research Group Database (CMRG-DB), an MM-specific database tracking patients with MM at 16 Canadian health care institutions. The investigators’ analysis focused on adult patients who received at least 1 line of therapy for MM between 2010 and 2020. Patients with amyloidosis or plasma cell leukemia were excluded.

That left 5548 patients, of whom 3111 received autologous stem cell transplants (ASCT) as their first-line therapy; 2437 received other therapies.

The data showed significantly lower rates of attrition than previously reported. Among patients receiving ASCT, the attrition rate was 7% after the first line of therapy, 12% after the second, and 23% after the third. Rates were somewhat higher among the non-ASCT group, but still below the previously reported figures. Among non-ASCT patients, there was a 19% attrition rate after line 1, 26% rate after line 2, and 40% rate after line 3.

Looking more closely, the investigators found only a minority of patients were living with progressive disease and opting against further treatment. For instance, in the non-ASCT cohort, although 19% of patients did not go on to second-line therapy, most attrition was due to death. Seventeen percent of patients in the non-ASCT cohort did not continue to second-line therapy due to death. Only 2% did not continue to further therapy despite progression.

When investigators looked at the most common reasons for attrition, they found older age, shorter time to progression, and inferior responses to therapy were the most significant independent risk factors for attrition. As with earlier studies, they found attrition rates increased with each line of therapy and that patients who received treatment other than ASCT had higher attrition rates.

The investigators said their study had notable limitations. For instance, they were not able to capture factors such as comorbidities that may have contributed to attrition rates. In addition, the time frame of their dataset limited their ability to factor in the latest scientific advances.

Even with those limitations, however, the investigators said their data indicate a need for a “revised definition of attrition which accounts for the fact that most patients who do not receive subsequent therapy are either continuing their current therapy and/or are in remission off-treatment—and therefore may be candidates for future regimens—rather than being lost to attrition.”

They said a more contextualized definition would help better direct future research efforts.

Reference

McCurdy A, Mian H, LeBlanc R, et al. Redefining attrition in multiple myeloma (MM): a Canadian Myeloma Research Group (CMRG) analysis. Blood Cancer J. Published online July 20. doi:10.1038/s41408-023-00883-x