ASH Clinical News July 2017 V2 - Page 12

DARZALEX ® ( daratumumab ) + Rd significantly improved PFS vs Rd alone 1

Superior efficacy in combination

DARZALEX ® ( daratumumab ) + Rd significantly 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 . Efficacy 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 first 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 .
Superior efficacy in combination DARZALEX ® (daratumumab) + Rd significantly improved PFS vs Rd alone 1 100 63 % 80 63 reduction in the risk of disease progression or with DARZALEX ® + Rd reduction in death the 60 risk of disease progression or death with POLLUX was an open-label, randomized, PRODUCT X + Rd 40 DARZALEX ® + Rd Rd 20 P<0.0001 HR=0.37 (95% CI: 0.27, 0.52) 0 0 91.3 % % 3 6 9 12 Months 15 18 21 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. Efficacy 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% 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. &CVƖF֖FRBFWWF6Se3&w&W76g&VR7W'ffò#ֆ&B&F%#fW&&W76R&FS5#6WFR&W76Sdu#fW'vB'F&W76S#'F&W76RखF6FD%U *F&GVV"2F6FVB6&FvFVƖF֖FRBFWWF6R"&'FW֖"@FWWF6Rf"FRG&VFVBbFVG2vFVFPזVvfR&V6VfVBBV7BR&"FW&ख'FB6fWGf&F4E$D4D3Pt$u2B$T4UD0gW6&V7F0D%U *66W6R6WfW&RgW6&V7F2&FVǐbbFVG2WW&V6VB&V7F7BGW&rFPf'7BgW6gW6&V7F26667W"vF7V'6WVV@gW62V&ǒ&V7F267W'&VBGW&rgW6"vFBW'2b6WFrgW6&"FFRG&GV7F`7B֖gW6VF6F6Ɩ6G&2gW6&V7F067W'&VBWFCW'2gFW"gW66WfW&R&V7F0fR67W'&VB6VFr'&676G7VW'FV6'vVVFVBV'VFV6v0B7F26VFR&W7&F'7F27V6266vW7F6VvF&B'&FF2vV262f֗FpBW6VW7267F2vW&RvVWrW&v0&F2&W6W7BF66f'B'W&GW2BFV6&RVF6FRFVG2vFF7F֖W2F&WF72@6'F67FW&G2g&WVVFǒF"FVG2GW&rFRVF&PgW6FW''WBgW6f"&V7F2b6WfW&G@7FGWFRVF6vVVB2VVFVBW&VFǐF66FVRFW&f"ƖfRF&VFVrw&FRB&V7F2f"FVG2vFw&FR""2&V7F2&VGV6RFRgW6&FRvV&R7F'FrFRgW6F&VGV6RFR&6bFVVBgW6&V7F2F֖7FW"&6'F67FW&G2FFVG2fvrD%U *gW62FVG2vF7F'b6&2'7G'V7FfRV'F6V6P&WV&RFFF7B֖gW6VF6F2FvP&W7&F'6Ɩ6F266FW"&W67&&r6'BBrЦ7Fr'&6FF'2BVB6'F67FW&G2f"FVG0vF6&2'7G'V7FfRV'F6V6RखFW&fW&V6RvF6W&v6FW7FpF&GVV"&G2F4C3&VB&B6V2$$72@&W7VG26FfRF&V7BFv'VƖFW7BF&V7B6'2FW7BF&GVV"VFFVB6FfRF&V7BFv'VƖFW7BW'67Bf"WFbF2gFW"FR7BF&GVV"gW6F&GVV"&VBF$$7262FWFV7FbF&FW0F֖"FvV2FRFVN( 26W'VFRFWFW&֖FbFVN( 2$B&&BGR&RB7FVBFg&@G&6gW66VFW'2bF2FW&fW&V6RvF6W&v6FW7Fr@f&&B&2FBFVB2&V6VfVBD%U *GPB67&VVFVG2&"F7F'FrD%U *WWG&VD%U *7&V6RWWG&VGV6VB'&6w&V@FW&F"6WFR&B6V6VG2W&F6ǒGW&pG&VFVB66&FrFVf7GW&W.( 2&W67&&rf&Ff"&6w&VBFW&W2F"FVG2vFWWG&Vf"6v2bfV7FD%U *F6RFV&R&WV&VBFr&V6fW'bWWG&2F6R&VGV7FbD%U *গ2&V6VFVB66FW"7W'FfR6&RvFw&wFf7F'2F&&7FVD%U *7&V6RF&&7FVGV6VB'&6w&VBFW&F"6WFR&B6V6VG0W&F6ǒGW&rG&VFVB66&FrFVf7GW&W.( 0&W67&&rf&Ff"&6w&VBFW&W2D%U *F6RFV&R&WV&VBFr&V6fW'bFVWG2F6R&VGV7FbD%U *2&V6VFVB66FW 7W'FfR6&RvFG&6gW62