Receiving the once-weekly KRd56 treatment regimen for relapsed or refractory multiple myeloma demonstrated no difference when compared with the twice-weekly KRd27 regimen.
Findings regarding the similarities between the two drug regimens were evaluated in a study published in Blood Advances. Between May 2019 and February 2022, researchers enrolled 454 eligible patients randomly assigned to receive either KRd56 or KRd27. The KRd56 group included 228 patients and the KRD27 group included 226 patients.
Of note, patients from the KRd56 group were treated once weekly and patients from the KRd27 group received treatment twice weekly.
The Effectiveness of KRd56 and KRd27 in Patients With Multiple Myeloma
Glossary
KRd56: a once-weekly regimen consisting of Kyprolis (carfilzomib) at 56 milligrams per square meter, Revlimid (lenalidomide) and dexamethasone.
KRd27: a twice-weekly treatment regimen consisting of Kyprolis (carfilzomib) at 27 milligrams per square meter, Revlimid (lenalidomide) and dexamethasone. It was once the standard of care for patients with relapsed or refractory multiple myeloma.
Overall response rate (ORR): percentage of patients who have a partial response to treatment (tumor shrinkage) or a complete response to treatment (tumor disappeared).
Minimal residual disease (MRD): remaining microscopic traces of tumor cells in the body.
Progression-free survival (PFS): time patients live without their cancer worsening or spreading.
Neutropenia: abnormally low levels of a type of white blood cell, essential for fighting infections.
Thrombocytopenia: low levels of platelets in the blood, essential for helping the body heal wounds.
The overall response rate (ORR), which was the study’s main goal, was 82.5% versus 86.3% in the once-weekly KRd56 and twice-weekly KRd27 groups, respectively. Researchers reported that there was no statistical significance between patients’ ORR in each group.
Most patients who demonstrated a complete response to treatment also showed minimal residual disease (MRD) negativity, which was similar among patients from the KRd56 and KRd27 groups.
“Minimal residual disease is a way to test how much disease is left behind in the body,” Dr. Henry Fung said in an interview with CURE®. “There are two ways to do MRD [testing]: by a flow cytometry study and next-generation sequencing.”
He noted that instead of looking for specific proteins under the microscope, using these additional tools helps detect potential residual disease in one of 1 million cells. This can help predict longer disease control and longer survival, he explained.
Fung is the chair of the Department of Bone Marrow Transplant and Cellular Therapies and director of the Multiple Myeloma Programs at Fox Chase Cancer Center in Philadelphia.
Another similarity among the two treatment groups was progression-free survival (PFS), of which the PFS was not reached in either group. When a PFS is not reached, it means the average amount of patients in each group did not experience disease worsening or spreading by the time data was collected.
At six months, the median PFS rates were 89.5% and 87.6% in the once-weekly KRd56 and twice-weekly KRd27 groups, respectively. At 12 months, the median PFS rates were 80.7% and 79.7%.
The Safety of KRd56 and KRd27
Side effects of any grade (severity) occurred in 209 patients and 219 patients from the once-weekly KRd56 and twice-weekly KRd27 groups, respectively. The most common treatment-emergent side effects that occurred included neutropenia, anemia, high blood pressure and thrombocytopenia.
Reported treatment-emergent side effects that were grade 3 (severe) or worse included neutropenia, thrombocytopenia, anemia, high blood pressure and pneumonia.
READ MORE: 10 Multiple Myeloma Questions and Answers: Treatments and Side Effects
Serious treatment-emergent side effects occurred in 84 patients from the once-weekly KRd56 group and 75 patients from the twice-weekly KRd27 group. These serious side effects were pneumonia, COVID-19 pneumonia and COVID-19 infection.
KRd56 and KRd27 Versus Other Multiple Myeloma Treatments
In the study, the efficacy and safety demonstrated respective similarities for the treatment of KRd56 and KRd27 in patients with relapsed or refractory multiple myeloma. However, it’s important to note that because KRd56 is received once weekly, it may make a significant difference in patients’ lives, Fung said.
“It is more for the convenience factor,” he explained. “It’s really difficult for patients to go to an infusion facility two times a week for the treatment. If they go down to one day for treatment, it will be much better. Patients have much better things to do than coming into the doctor’s office.”
Fung emphasized that this study solely focused on only KRd56 and KRd27 and showed similar effectiveness in patients. Nonetheless, because these treatment regimens have been used for many years, “it’s already irrelevant.”
Now, he said that there are many treatment options for patients with relapsed or refractory multiple myeloma. Although it’s common for patients to experience a relapse after having treatment, he noted that it’s possible for patients to be in remission for seven to eight years.
“We have patients who have gone on for 15 years who are still disease-free, so maybe [multiple myeloma] can be curable, but we don’t have enough data to declare a cure yet.”
Some of these treatment options include the anti-CD38 monoclonal antibody, “which should be included in every single salvage regimen nowadays and also has recently become the standard of care recently for frontline treatment,” Fung said.
Other treatments include three immunomodulating agents, Fung explained.
“[These] three immunomodulating agents are [Thalomid (thalidomide)], [Pomalyst (pomalidomide)] and [Revlimid (lenalidomide)],” he stated.
“The one [drug] that patients have not seen [or have been treated with] before will be the best treatment option. It will also depend on what other [treatment] that will be used, and that will depend on what treatment patients were refractory to in their [previous] treatment.”
Reference
“A.R.R.O.W.2: once- vs twice-weekly carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma” by Meletios A, Dimopoulos, et al., Blood Advances.
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