A New Treatment Option for Relapsed/Refractory Multiple Myeloma

In patients with relapsed or refractory multiple myeloma, researchers have found that adding the drug daratumumab to the combination of carfilzomib and dexamethasone led to better outcomes when compared with carfilzomib and dexamethasone alone.

The term “relapsed” refers to patients whose cancer reappeared or grew again after a period of remission. “Refractory” is used to describe a person whose cancer did not respond to treatment (meaning that their cancer cells continued to grow) or whose response to treatment did not last very long.

This finding is based on results from the phase 3 CANDOR trial. The 3-drug combination improved progression-free survival in patients, which is a sign of an effective treatment. Progression-free survival is the length of time that a person lives with their cancer without it getting any worse.

Clinical trials are designed to test the safety and effectiveness of new drugs, and phase 3 clinical trials like CANDOR are carried out to confirm and expand on safety and effectiveness results from phase 1 and 2 trials, to compare the new treatment with the standard therapies that have already been approved, and to study the overall risks and benefits of the drug. Trials in this phase can last years, and can involve thousands of people.

Although survival in multiple myeloma has greatly improved with the approval of new therapies in recent years, it is still incurable, and most patients will eventually relapse. But patients who received this new treatment were 37% less likely to die or to have cancer progression than patients who were given carfilzomib and dexamethasone alone.

“Daratumumab, carfilzomib and dexamethasone represents an efficacious new regimen for relapsed/refractory multiple myeloma, including in lenalidomide-exposed and lenalidomide-refractory patients,” said Dr. Saad Z. Usmani, one of the study’s lead investigators. This is important because lenalidomide is a very common treatment for multiple myeloma, so people who do not respond to lenalidomide now have more treatment options.

To qualify for the study, patients had to be relapsed or refractory after 1 to 3 previous lines of therapy. A total of 312 patients were given the 3-drug combo, and 154 patients were given carfilzomib and dexamethasone alone.

At about 16 months, more than half of the patients who were given carfilzomib and dexamethasone alone had cancer progression (worsening), but most patients in the 3-drug group had not had a worsening of their cancer.

Patients treated with the 3-drug combination also had nearly 10 times higher rates of minimal residual disease (MRD)-negativity: 12.5% versus 1.3%. MRD is a term used to describe the small number of cancer cells in the body after cancer treatment, so an MRD-negative result means that no disease was detected after treatment. Doctors use MRD to measure the effectiveness of treatment and to predict which patients are at risk of relapse.

Patients in the 3-drug group did have slightly higher rates of serious side effects, but the rates of treatment discontinuations were about the same in both groups. Overall, the researchers found the experimental drug combination to be tolerable. Five deaths were related to treatment, and these were all in the daratumumab, carfilzomib, and dexamethasone group.

However, the frequency of grade 3 or worse heart failure was lower in the 3-drug group, at 3.9% versus 8.5% in the 2-drug arm (grade 3 side effects are severe or medically significant, but not immediately life-threatening).

The investigators said they are not sure why this happened, but are doing further research into patient factors (such as other health conditions people might have had prior to the study) that could have contributed.

“Daratumumab, carfilzomib and dexamethasone should be considered as a novel, efficacious, and tolerable treatment option for relapsed/refractory multiple myeloma,” said Dr. Usmani.