Optimizing Treatment for Patients With Relapsed Multiple Myeloma
At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, cutting edge research and paradigm-changing data were presented across different tumor types, including multiple myeloma. Some of the new findings from the phase III clinical trials in relapsed refractory multiple myeloma (RRMM) will likely impact current practice.
Substantial Benefit of Adding Pomalidomide to Bortezomib/Dexamethasone in Lenalidomide Pretreated Patients
The immunomodulatory drug (IMiD) lenalidomide is an established therapy for patients with newly diagnosed multiple myeloma, but many patients become lenalidomide-resistant after one or two lines of treatment. Pomalidomide, a next-generation IMiD, has been shown to be effective in lenalidomide-refractory patients when given in combination with low-dose dexamethasone. The phase III OPTIMISMM trial (N = 559) evaluated the addition of pomalidomide to bortezomib and low-dose dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy, at least one of which included lenalidomide.
The addition of pomalidomide to Vd resulted in a 39% reduction in the risk of progression and death compared to Vd alone. The median progression-free survival was 11.2 months with pomalidomide plus Vd, compared to 7.1 months with Vd alone (HR 0.61, P<.0001). In the setting of first relapse, the addition of pomalidomide to Vd resulted in a 9.1-month improvement in PFS, from 11.63 months with Vd to 20.73 months with pomalidomide plus Vd (HR 0.54, P = .0027). The objective response rate (ORR) was significantly higher in patients receiving pomalidomide plus Vd, compared to Vd alone (82.2% vs 50.0%; P<.001). The toxicity profile was consistent with the known safety profile of these agents. The most common grade 3/4 adverse events (AEs) associated with pomalidomide included neutropenia (41.7% vs 8.5%) and infections (30.9% vs 17.8%).
Presenter Paul Richardson, MD (Dana-Farber Cancer Institute, Boston, Massachusetts, United States), concluded by saying that patients with relapsed/refractory multiple myeloma who have progressed on lenalidomide represent a growing population with a high need for novel therapeutic options, and the results from OPTIMISMM support the use of pomalidomide in combination with bortezomib and dexamethasone in this setting. Further analysis of this trial, including long-term survival, is ongoing.
Once-Weekly Carfilzomib Superior to Twice-Weekly Carfilzomib
The proteasome inhibitor carfilzomib is approved for relapsed/refractory multiple myeloma at a dose of 27 mg/m2 given twice weekly. To improve the convenience of carfilzomib, the phase III ARROW trial (N = 478) compared a once-weekly carfilzomib (70 mg/m2) to the standard twice-weekly schedule (27 mg/m2) in patients with relapsed/refractory multiple myeloma. Carfilzomib was given at a dose of 20 mg/m2 for the first week and 70 mg/m2 for all subsequent weeks. All patients also received dexamethasone 40 mg weekly.
Once-weekly carfilzomib resulted in a significant improvement in PFS, compared to twice-weekly carfilzomib (11.2 months vs 7.6 months; HR 0.693, P = .0029). This benefit was consistent across all patient subgroups, including the patients who were refractory to bortezomib. The ORR was 62.9% with once-weekly carfilzomib, compared to 40.8% with twice-weekly carfilzomib (P<.0001). The median overall survival (OS) has not been reached in either treatment arm. Rates of AEs were similar between the two treatment groups. Grade 3/4 treatment-related AEs occurred in 68% of patients receiving the once-weekly schedule and 62% of patients receiving the twice-weekly schedule.
Presenter Maria-Victoria Mateos, MD, PhD (University Hospital of Salamanca, Salamanca, Spain), concluded that these results support the use of a once-weekly 70 mg/m2 schedule of carfilzomib over the standard twice-weekly schedule, as the once-weekly schedule is more convenient for patients and results in improved outcomes with no additional toxicities. Results of this study were simultaneously published in Lancet Oncology.