Treatment with Kyprolis (carfilzomib) once a week is as safe and effective as the twice-weekly regimen used for the initial treatment of multiple myeloma patients, a study of two clinical trials suggests.
Kyprolis, developed by Amgen, is a proteasome inhibitor — a treatment that allows defective proteins to accumulate in cells, leading to their death — used to treat multiple myeloma patients.
Kyprolis was approved initially for relapsed or refractory patients in a twice-weekly schedule. However, schedules that involve fewer visits to the hospital while providing similar effects are more practical for patients and increase the number who complete the treatment.
In a prior Phase 3 trial, ARROW (NCT02412878), researchers found that a once-weekly dose of 70 mg/m² Kyprolis was superior to twice-weekly 27 mg/m² for relapsed or refractory multiple myeloma patients, without increasing toxicity.
However, a major limitation of this trial was that patients on the twice-weekly regimen received an overall lower dose, compared to those on once-weekly dosing. So, researchers decided to compare data from two trials assessing similar doses of Kyprolis in newly diagnosed multiple myeloma patients who were not eligible for a stem cell transplant.
The IST-CAR-561 Phase 1/2 trial (NCT01857115) used 70 mg/m² of Krypolis once a week and the IST-CAR-506 Phase 2 trial (NCT01346787) used 36 mg/m² of Krypolis twice weekly. Preliminary results of both trials have shown that the treatment is safe and effective.
Researchers polled data from both trials to compare the safety and effectiveness of the two regimens. They evaluated 121 patients who received nine induction cycles of a combination of Kyprolis, cyclophosphamide, and dexamethasone, followed by maintenance with Kyprolis at the same dose and schedule.
The proportion of patients responding to treatment was 90% in the once-weekly regimen, versus 90% for the twice-weekly group. Complete responses were obtained by 22% and 29% of patients, respectively.
The time patients lived without disease worsening was similar in both groups — 35.7 months for once-weekly versus 35.5 months for twice-weekly Kyprolis — as was the time to disease progression on a second anti-myeloma treatment.
Overall, 70% of patients in the once-weekly group survived three years or longer, which was similar to the 72% of patients in the twice-weekly group. Overall survival after starting maintenance therapy also was similar with 72% of patients in the once-weekly group and 73% in the twice-weekly group surviving three or more years.
Both groups presented a similar safety profile: 24% of patients in the once-weekly group showed blood-related adverse side effects versus 30% in the twice-weekly group. The percentage of patients that presented side effects that were not blood-related were 38% and 41%, respectively.
The most common side effects leading to dose reduction were kidney injury or infection and high blood pressure. The main side effects leading to treatment discontinuation were heart injury, infections, and blood clots. The occurrence of side effects was similar in the two groups.
“Once-weekly 70 mg/m2 carfilzomib, as induction and maintenance therapy for newly diagnosed multiple myeloma patients, was as safe and effective as twice-weekly 36 mg/m2 carfilzomib and provided a more convenient schedule,” researchers said.
“A shift from the current twice-weekly to a once-weekly dosing schedule would decrease by 50% the patient visits to healthcare facilities, with a subsequent improvement in the quality of life and a reduction in drug and health care costs,” they added.
Clinical trials specifically designed to compare the safety and effectiveness of the two schedules in newly-diagnosed patients are necessary to validate the results of this study fully, they recommended.