Carfilzomib, Pomalidomide, and Dex (KPd) in High-Risk Myeloma Patients

Results of maintenance therapy on high-risk myeloma

Dr. Ajay Nooka presented the results of a study on maintenance therapy for high-risk myeloma patients at ASCO 2023. The study focused on the combination maintenance therapy with Carfilzomib, Pomalidomide, and Dexamethasone (KPd regimen). The study aimed to evaluate the efficacy and safety of this maintenance therapy approach.

• The study included cytogenetically defined high-risk myeloma patients who have poor progression-free survival (PFS) and overall survival compared to standard-risk patients.
• The median PFS for high-risk patients was 42 months, while standard-risk patients had a median PFS of 77 months.
• The study employed a combination maintenance strategy with the KPd regimen, which showed promising results in previous trials.
• The trial included patients with specific high-risk cytogenetic abnormalities, such as deletion 17p, translocation 4;14, translocation 14;16, or the presence of primary plasma cell leukemia.
• The induction therapy was left up to the physician's choice, and patients who received stem cell transplants were enrolled within 12 months of diagnosis.
• The combination maintenance therapy consisted of Carfilzomib, Pomalidomide, and Dexamethasone, administered for three years or until disease progression.
• The primary endpoint of the study was the greater than complete response rate, which was achieved in 89.7% of patients.
• The secondary endpoints included minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS).
• The MRD negativity rate at the threshold of 10^(-6) was seen in 66.7% of patients, while 90% of patients achieved MRD negativity at the threshold of 10^(-5).
• The median PFS and overall survival were not reached at a median follow-up of 30.5 months from study entry and 40 months from the initial diagnosis.
• Patients with double-hit disease or multiple high-risk cytogenetic abnormalities had a shorter median PFS.
• The safety profile of the combination maintenance therapy showed common adverse events such as hypophosphatemia, muscle cramps, hypomagnesemia, headaches, agitation, and rash.
• Hematological toxicities, including neutropenia, anemia, and thrombocytopenia, were observed but managed with dose reductions.
• Non-hematological adverse events of interest included cataracts and renal failure, which occurred in a small percentage of patients.
• Progressive disease remained the major cause of mortality in the study, and a few patients discontinued the trial due to adverse events or personal choice.
• The results of the study compare favorably with previous trials using different maintenance strategies, demonstrating high response rates and improved survival outcomes.
• These findings support the use of combination maintenance strategies, like the KPd regimen, for high-risk myeloma patients.

Authors:
Ajay K. Nooka, Nisha S Joseph, Madhav V. Dhodapkar, Craig C. Hofmeister, Vikas Anand Gupta, Joel S Andrews, Charise Gleason, Anuja A Sharma, Bryan J Burton, Quanta R Cato, Ching Siong Tey, Manali Rupji, Yuan Liu, Ian McFadden, Rani Najdi, Lawrence H Boise, Jonathan L. Kaufman, Sagar Lonial

Clinical trial information: NCT03756896