Merck, known as MSD outside the United States and Canada, has announced new study findings investigating the use of Keytruda ( Pembrolizumab ), an anti-PD-1 therapy, in combination with Lenalidomide and low-dose Dexamethasone ( two commonly used treatments for multiple myeloma ) in patients whose disease has progressed after at least two lines of prior therapy, including a proteasome inhibitor and an IMiD ( immune modulatory drug ).
The initial findings from the ongoing phase 1 KEYNOTE-023 study showed an overall response rate ( ORR ) of 76% ( n=13/17 ), as assessed by the International Myeloma Working Group ( IMWG ) 2006 Criteria.
These results were presented at the 57th American Society of Hematology ( ASH ) Annual Meeting. Based in part on these data, Merck has initiated two phase 3 studies evaluating Keytruda in the treatment of multiple myeloma.
In the study with 50 heavily pre-treated patients, initial findings from 17 patients who were treated with Pembrolizumab in combination with Lenalidomide and low-dose Dexamethasone demonstrated an ORR of 76% ( n=13/17 ) ( per IMWG 2006 ), including four very good partial responses ( 24% ) and nine partial responses ( 53% ).
Adverse events in all 50 patients were consistent with previously reported safety data for Pembrolizumab as well as Lenalidomide and low-dose Dexamethasone.
Grade 3 or 4 treatment-related adverse events included: neutropenia ( n=11 ), thrombocytopenia ( n=4 ), diarrhea ( n=1 ), fatigue ( n=1 ), anemia ( n=4 ), hyperglycemia ( n=3 ) and muscle spasms ( n=1 ).
Immune-mediated adverse events included: adrenal insufficiency ( n=1 ), hyperthyroidism ( n=2 ), hypothyroidism ( n=2 ), and thyroiditis ( n=1 ). No treatment-related deaths were reported.
KEYNOTE-023 is a global, open-label, phase 1 study designed to evaluate Keytruda treatment in combination with Dexamethasone and two different doses of Lenalidomide in approximately 75 patients with relapsed / refractory multiple myeloma ( RRMM ).
Patients will receive Pembrolizumab ( 2 mg/kg every two weeks ) in combination with Lenalidomide ( 10 mg or 25 mg ) or Pembrolizumab ( 200 mg fixed dose every two weeks ) with Lenalidomide ( 10 mg or 25 mg ); all patients will receive 40 mg low-dose Dexamethasone weekly.
Primary endpoints include safety and tolerability; secondary endpoints include ORR, duration of response, progression-free survival ( PFS ), and overall survival ( OS ).
Multiple myeloma is a cancer of blood plasma cells in which abnormal plasma cells multiply uncontrollably in the bone marrow and occasionally in other parts of the body. Manifestations of the disease often include bone pain and fractures, and may include kidney problems, a weakened immune system weakness, and confusion.
Multiple myeloma is the second most common blood cancer. In 2015, an estimated 26,850 people are expected to be diagnosed and an estimated 11,240 people are expected to die of the disease in the U.S. alone.
Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.
Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with metastatic non-small cell lung cancer ( NSCLC ) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after Platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda.
Keytruda is also indicated at the same dosing for the treatment of patients with unresectable or metastatic melanoma and disease progression following Ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. ( Xagena )
Source: Merck & Co, 2015