In recent months, the U.S. Food and Drug Administration (FDA) granted approvals to two multiple myeloma (MM) treatments, one paroxysmal nocturnal hemoglobinuria (PNH) treatment, and one acute lymphoblastic leukemia (ALL) treatment.
MM Approvals
Both idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are now approved to treat MM in adult patients, though the indications differ.
Ide-cel is indicated to treat relapsed or refractory (R/R) MM in adult patients who have had at least two prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
The treatment is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor T-cell therapy that was approved based on the results of the KarMMa-3 study. Data demonstrated a 71% overall response rate and a median progression-free survival (PFS) of 13.3 months.
Common adverse events (AEs) included cytokine release syndrome (CRS; 89%) and neurotoxicity (40%).
Cilta-cel is indicated to treat R/R MM in adult patients who are refractory to lenalidomide and have had at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Cilta-cel is a BCMA-targeted therapy that was approved based on the results of a phase III CARTITUDE-4 study. Data demonstrated a reduced risk of disease progression or death by 59% compared to standard therapies.
Common adverse reactions included CRS, neurotoxicity, pyrexia, nausea, neutropenia, anemia, lymphopenia, edema, dizziness, decreased white blood cell count, thrombocytopenia, vomiting, hypotension, upper respiratory tract infection, constipation, dyspnea, hypogammaglobulinemia, tachycardia, coagulopathy, encephalopathy, viral infections, and infections-pathogen unspecified.
Cilta-cel was granted approval in February 2022 to treat R/R MM in adults who have received at least four lines of prior therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
“[Cilta-cel] demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of R/R MM as shown through the CARTITUDE-4 study results,” said Binod Dhakal, MD, associate professor in the Division of Hematology and Oncology at the Medical College of Wisconsin. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their MM as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”
PNH Approval
Danicopan was approved as an add-on therapy to ravulizumab or eculizumab to treat extravascular haemolysis (EVH) in adults with PNH. The treatment is an oral factor D inhibitor.
Approval was based on the results of a phase III trial dubbed ALPHA that found the treatment met the primary endpoint of change in hemoglobin as well as all secondary endpoints. Nausea, diarrhea, headache, and arthralgia were common treatment-emergent AEs.
Before approval, danicopan was granted breakthrough therapy and orphan drug designations by the FDA and PRIority MEdicines (PRIME) status and orphan drug designation by the European Medicines Agency; it has been approved in Japan following orphan drug designation.
ALL Approval
Ponatinib was granted accelerated approval to treat newly diagnosed Philadelphia chromosome-positive (Ph+) ALL with chemotherapy in adult patients. The treatment is a tyrosine kinase inhibitor (TKI) that targets BCR::ABL1.
Approval was granted based on the results of a randomized, active-controlled, multicenter, open-label trial dubbed PhALLCON. Results demonstrated a measurable residual disease-negative complete response (CR) rate of 30%.
Common adverse reactions included abdominal pain, arthralgia, cardiac arrhythmias, febrile neutropenia, fluid retention and edema, hemorrhage, hepatic dysfunction, hypertension, nausea, oral mucositis, pancreatitis/elevated lipase, paresthesia, peripheral neuropathy, pyrexia, and vomiting.
Ponatinib was previously granted priority review and orphan drug designation.
“Ph+ ALL is an extremely aggressive cancer, and patients with this disease suffer from poor outcomes. There has long been a need for a potent TKI that can suppress mutation development and elicit deep responses in the frontline,” said Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center and lead investigator of the PhALLCON trial. “Ponatinib may help address these factors and impact long-term outcomes.”
Sources:
AstraZeneca, April 1, 2024.
Business Wire, April 5, 2024.
PR Newswire, April 5, 2024.
Takeda, March 19, 2024.
FDA, March 19, 2024.
