DARZALEX ® ( daratumumab ) + Rd signi�cantly improved PFS vs Rd alone 1
Superior ef� cacy in combination
DARZALEX ® ( daratumumab ) + Rd signi�cantly improved PFS vs Rd alone 1
100
80
63
%
PFS (%)
60
40
20
DARZALEX ® + Rd Rd
P < 0.0001 HR = 0.37 ( 95 % CI : 0.27 , 0.52 )
0 0 3 6 9 12 15 18 21 Months reduction in the risk of disease progression or death with DARZALEX ® + Rd
POLLUX was an open-label , randomized , active-controlled phase 3 trial comparing treatment with DARZALEX ® 16 mg / kg + Rd ( n = 286 ) to Rd alone ( n = 283 ) in multiple myeloma patients who received a minimum of 1 prior therapy . Patients receiving DARZALEX ® were treated with pre- and post-infusion medications . Patients were treated until unacceptable toxicity or disease progression . Ef� cacy was evaluated by PFS based on International Myeloma Working Group ( IMWG ) criteria . 1
ORR with DARZALEX ® + Rd vs 74.6 % with Rd alone ( P < 0.0001 ). CR or better was 42.3 % with DARZALEX ® + Rd vs 18.8 %
91.3 % with Rd alone . VGPR was 32.2 % vs 24.4 %, and PR was 16.8 % vs 31.4 % with DARZALEX ® + Rd vs Rd alone , respectively . 1
Rd = lenalidomide and dexamethasone ; PFS = progression-free survival ; HR = hazard ratio ; ORR = overall response rate ; CR = complete response ; VGPR = very good partial response ; PR = partial response .
Indication
DARZALEX ® ( daratumumab ) is indicated in combination with lenalidomide and dexamethasone , or bortezomib and dexamethasone , for the treatment of patients with multiple myeloma who have received at least one prior therapy .
Important Safety Information
CONTRAINDICATIONS : None
WARNINGS AND PRECAUTIONS
Infusion Reactions
DARZALEX ® can cause severe infusion reactions . Approximately half of all patients experienced a reaction , most during the � rst infusion . Infusion reactions can also occur with subsequent infusions . Nearly all reactions occurred during infusion or within 4 hours of completing an infusion . Prior to the introduction of post-infusion medication in clinical trials , infusion reactions occurred up to 48 hours after infusion . Severe reactions have occurred , including bronchospasm , hypoxia , dyspnea , hypertension , laryngeal edema and pulmonary edema . Signs and symptoms may include respiratory symptoms , such as nasal congestion , cough , throat irritation , as well as chills , vomiting and nausea . Less common symptoms were wheezing , allergic rhinitis , pyrexia , chest discomfort , pruritus , and hypotension .
Pre-medicate patients with antihistamines , antipyretics , and corticosteroids . Frequently monitor patients during the entire infusion . Interrupt infusion for reactions of any severity and institute medical management as needed . Permanently discontinue therapy for life-threatening ( Grade 4 ) reactions . For patients with Grade 1 , 2 , or 3 reactions , reduce the infusion rate when re-starting the infusion .
To reduce the risk of delayed infusion reactions , administer oral corticosteroids to all patients following DARZALEX ® infusions . Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications . Consider prescribing short- and longacting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease .
Interference with Serological Testing
Daratumumab binds to CD38 on red blood cells ( RBCs ) and results in a positive Indirect Antiglobulin Test ( Indirect Coombs test ). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion . Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient ’ s serum . The determination of a patient ’ s ABO and Rh blood type are not impacted . Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX ® . Type and screen patients prior to starting DARZALEX ® .
Neutropenia
DARZALEX ® may increase neutropenia induced by background therapy . Monitor complete blood cell counts periodically during treatment according to manufacturer ’ s prescribing information for background therapies . Monitor patients with neutropenia for signs of infection . DARZALEX ® dose delay may be required to allow recovery of neutrophils . No dose reduction of DARZALEX ® is recommended . Consider supportive care with growth factors .
Thrombocytopenia
DARZALEX ® may increase thrombocytopenia induced by background therapy . Monitor complete blood cell counts periodically during treatment according to manufacturer ’ s prescribing information for background therapies . DARZALEX ® dose delay may be required to allow recovery of platelets . No dose reduction of DARZALEX ® is recommended . Consider supportive care with transfusions .