Use of Triplet Therapy Rose in R/R MM as Deaths Declined, Study Finds

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Newer therapies have led to a boost in the number of patients with relapsed or refractory multiple myeloma (R/R MM) who are prescribed triplet regimens. As that shift has occurred, death rates appear to have dropped.

More and more patients with relapsed or refractory multiple myeloma (R/R MM) are being treated with triplet therapies, and that change has resulted in an increase in survival and decrease in hospitalizations, according to a new study of a German data set.

The findings, published in the European Journal of Haematology, help to underscore the impact of new therapies on the treatment of MM worldwide.

Investigators from 2 German universities and Takeda Pharmaceutical Co. noted that drugs like lenalidomide (Revlimid) and bortezomib (Velcade) have typically been given as part of doublet therapy over the past 15 years. However, a spate of newer therapies, including the proteasome inhibitor (PI) carfilzomib (Kyprolis) and the monoclonal antibody (mAb) daratumumab (Darzalex) have typically been given in triplet combinations.

Existing data suggests uptake of these newer drugs is on the rise, but corresponding author Christof Scheid, MD, of the University Hospital of Cologne, and colleagues noted that, “it remains to be determined whether the increased use of triplet-based therapy regimens including these new agents has resulted in improved clinical outcomes.”

To answer the question, the authors consulted a database from the Institute for Applied Health Research, which contains deidentified health data from 7 million Germans. The authors searched for patients with R/R MM who had at least one new prescription or therapeutic regimen during the years 2014 through 2017. Patients with a newly initiated therapy within 12 months of the start date of the study period were excluded.

The data yielded 1255 patients with R/R MM. They were divided into 6 therapy-based categories: immunomodulatory drug (IMiD)–based doublets, PI-based doublets, daratumumab monotherapy, PI-IMiD–based triplets, mAb-based triplets, and other treatments.

The authors sought to quantify use of the varying therapies, track changes over time, and see what impact, if any, those changes had on patient outcomes.

The data showed a dramatic shift. Triplet-based regimens were used in just 5.9% of cases in 2014, but by 2017 that number had jumped to 31.4%. Meanwhile, IMiD-based doublets were used in 74.3% of cases in 2014, but use of that regimen fell to 37.6% by 2017.

Over that same period of time, risk of death dropped by 32%, the authors said, and risk of hospitalization fell by 30%.


Though the proportions changed significantly, when taken as an overall patient population, the data showed that 70% of patients received doublet-based therapy, while just 18.6% received triplet-based therapy.

Scheid and colleagues wrote that it is not possible to say for sure that the new therapies and the use of triplet regimens are the cause, or the only cause, of the improved outcomes. For instance, changes to treatment guidelines or improvements in supportive care may also have played a role, they wrote.

“Furthermore, the availability of new agents and thus, much broader treatment repertoire and strategies allows timely and more efficacious interventions at each relapse phase,” they wrote.

The investigators also noted that there are a number of ways in which their studies are different from the phase 3 trials of the respective therapies, thus a direct comparison with data from those phase 3 trials is not possible.

Still, the authors said the data shows a clear trend toward triplet use, which appears to be benefiting patients. The investigators said the risks of adverse events did not change as the treatment regimens did.


Scheid C, Blau IW, Sellner L, Ratsch BA, Basic E. Changes in treatment landscape of relapsed or refractory multiple myeloma and their association with mortality: Insights from German claims database. Eur J Haematol. Published online September 28, 2020. doi:10.1111/ejh.13523. doi:10.1111/ejh.13523