Melphalan flufenamide has been added to the Multiple Myeloma Clinical Practice Guidelines of the National Comprehensive Cancer Network, for the treatment of adult patients with relapsed or refractory multiple myeloma who have had at least 4 prior lines of therapy.
Melphalan flufenamide (Pepatxo) has been added to the Multiple Myeloma Clinical Practice Guidelines of the National Comprehensive Cancer Network (NCCN), for the treatment of adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have had at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody, according to a press release from melphalan flufenamide’s developer, Oncopeptides AB.
The peptide-drug conjugate, melphalan flufenamide was approved by the FDA in February of 2021 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. The drug works by rapidly delivering an alkylating payload into cancer tumor cells. It is especially effective for treating myeloma, as myeloma cells have high lipophilicity. After the payload is inside the tumor cell, the activity of melphalan flufenamide is determined by its immediate cleavage by peptidases into the entrapped hydrophilic alkylators. The increase in intracellular alkylator concentration makes melphalan flufenamide 50-fold more potent than melphalan alone.
The approval of the combination of melphalan flufenamide and dexamethasone was based on the results of the HORIZON study (NCT02963493), a single arm, open-label study which enrolled 157 patients with relapsed/refractory multiple myeloma who are refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. The primary outcome of the study was overall response rate (ORR), which was measured from date of response until date of first documented progression or date of death, whichever came first, as assessed up to 24 months. Secondary outcomes included progression free survival (PFS), duration of response, (DOR), overall survival (OS), and safety.
In order to be eligible to participate, patients must be at least 18 years old with a prior diagnosis of multiple myeloma with documented disease progression. Additionally, patients must have at least 2 prior lines of therapy including an immunomodulatory imide drug (IMiD) and a PI as well as being refractory to pomalidomide (Pomalyst) and/or daratumumab (Darzalex). Participants also must have a life expectancy of 6 months or more. Patients with mucosal or internal bleeding and/or is refractory to platelet transfusion were excluded.
Of the 157 patients enrolled, 131 received melphalan flufenamide and dexamethasone. At the time of cutoff, 26 patients were still receiving treatment. According to the results, the ORR was 29% (95% CI, 22%-37%) in the overall population and 26% (95% CI, 18%-35) in the triple-class refractory population. In the all-treated population, the DOR was 5.5 months (95% CI, 3.9-7.6) and 4.4 months (95% CI, 3.4- 7.6) in the triple-class refractory population. Similar benefits were seen with PFS. Median PFS in the all-treated group was 4.2 months 95% CI, 3.4- 4.9) and 3.9 months (95% CI, 3.0-4.6) in the triple-class refractory group. The OS was 11.6 months and 11.2 months respectively.
"The NCCN Guidelines are a trusted resource for clinicians in the management of oncology patients," said Mohamed Ladha, general manager of the US Business Unit, at Oncopeptides, in a press release. "We are truly honored that Pepaxto has been added to these esteemed guidelines and we thank NCCN for this recognition."
NCCN is an alliance of 30 cancer centers in the United States. The organization’s Clinical Practice Guidelines in Oncology are meant to document evidence-based, consensus-driven disease management in order to help guide practitioners and patients in choosing the most effective treatment.