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FDA breakthrough therapy designation
A BTK inhibitor for the treatment of adult patients with MCL who have received at least one prior therapy … 1

CALQUENCE

GO STRONG

FOCUSED ON EFFICACY WITH DURABLE RESPONSES IN R / R MCL 1
80 % ORR [ 95 % CI : 72 , 87 ] / 40 % CR [ 95 % CI : 31 , 49 ] / IRC-assessed per 2014 Lugano classification * / Median DoR not reached at 15.2 month median follow-up
INDICATION AND USAGE
CALQUENCE is a Bruton tyrosine kinase ( BTK ) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma ( MCL ) who have received at least one prior therapy .
This indication is approved under accelerated approval based on overall response rate . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials .
IMPORTANT SAFETY INFORMATION Hemorrhage
Serious hemorrhagic events , including fatal events , have occurred in the combined safety database of 612 patients with hematologic malignancies treated with CALQUENCE monotherapy . Grade 3 or higher bleeding events , including gastrointestinal , intracranial , and epistaxis , have been reported in 2 % of patients . Overall , bleeding events , including bruising and petechiae of any grade , occurred in approximately 50 % of patients with hematological malignancies .
The mechanism for the bleeding events is not well understood .
CALQUENCE may further increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies , and patients should be monitored for signs of bleeding .
Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre- and post-surgery , depending upon the type of surgery and the risk of bleeding .
Infection Serious infections ( bacterial , viral , or fungal ), including fatal events and opportunistic infections , have occurred in the combined safety database of 612 patients with hematologic malignancies treated with CALQUENCE monotherapy . Grade 3 or higher infections occurred in 18 % of these patients . The most frequently reported Grade 3 or 4 infection was pneumonia . Infections due to hepatitis B virus ( HBV ) reactivation and progressive multifocal leukoencephalopathy ( PML ) have occurred .
Monitor patients for signs and symptoms of infection
and treat as medically appropriate . Consider prophylaxis in patients who are at increased risk for opportunistic infections .
Cytopenias
In the combined safety database of 612 patients with hematologic malignancies , patients treated with CALQUENCE monotherapy experienced Grade 3 or 4 cytopenias , including neutropenia ( 23 %), anemia ( 11 %), and thrombocytopenia ( 8 %), based on laboratory measurements . Monitor complete blood counts monthly during treatment .
Second Primary Malignancies
Second primary malignancies , including non-skin carcinomas , have occurred in 11 % of patients with hematologic malignancies treated with CALQUENCE monotherapy in the combined safety database of 612 patients . The most frequent second primary malignancy was skin cancer , reported in 7 % of patients . Advise protection from sun exposure .
Atrial Fibrillation and Flutter
In the combined safety database of 612 patients with hematologic malignancies treated with CALQUENCE monotherapy , atrial fibrillation and atrial flutter of any grade occurred in 3 % of patients , and Grade 3 in 1 % of patients . Monitor for atrial fibrillation and atrial flutter and manage as appropriate .
ADVERSE REACTIONS
The most common adverse reactions ( ≥20 %) of any grade were anemia ,* thrombocytopenia ,* headache ( 39 %), neutropenia ,* diarrhea ( 31 %), fatigue ( 28 %), myalgia ( 21 %) and bruising ( 21 %).
* Treatment-emergent decreases ( all grades ) of hemoglobin ( 46 %), platelets ( 44 %), and neutrophils ( 36 %) were based on laboratory measurements and adverse reactions .
The most common Grade ≥3 non-hematological adverse reaction ( reported in at least 2 % of patients ) was diarrhea ( 3.2 %).
Dosage reductions or discontinuations due to any adverse reaction were reported in 1.6 % and 6.5 % of patients , respectively .
Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8 % of patients .
DRUG INTERACTIONS
Strong CYP3A Inhibitors : Avoid co-administration with a strong CYP3A inhibitor . If a strong CYP3A inhibitor will be used short-term , interrupt CALQUENCE .
Moderate CYP3A Inhibitors : When CALQUENCE is co-administered with a moderate CYP3A inhibitor , reduce CALQUENCE dose to 100 mg once daily .
Strong CYP3A Inducers : Avoid co-administration with a strong CYP3A inducer . If a strong CYP3A inducer cannot be avoided , increase the CALQUENCE dose to 200 mg twice daily .
Gastric Acid Reducing Agents : If treatment with a gastric acid reducing agent is required , consider using an H2-receptor antagonist or an antacid . Take CALQUENCE 2 hours before taking an H2-receptor antagonist . Separate dosing with an antacid by at least 2 hours .
Avoid co-administration with proton pump inhibitors . Due to the long-lasting effect of proton pump inhibitors , separation of doses may not eliminate the interaction with CALQUENCE .
SPECIFIC POPULATIONS
There is insufficient clinical data on CALQUENCE use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage . Advise women of the potential risk to a fetus .
It is not known if CALQUENCE is present in human milk . Advise lactating women not to breastfeed while taking CALQUENCE and for at least 2 weeks after the final dose .
* Tumor response was assessed according to the Lugano classification for non-Hodgkin ’ s lymphoma ( NHL ).
CR = complete response ; DoR = duration of response ; IRC = Independent Review Committee ; ORR = overall response rate ( defined as the proportion of patients who achieved a CR or PR ); PR = partial response ; R / R = relapsed / refractory .
Reference : 1 . CALQUENCE [ package insert ]. Wilmington , DE : AstraZeneca Pharmaceuticals LP ; 2017 .
Please see Brief Summary of complete Prescribing Information on adjacent pages .
VISIT CALQUENCE . COM
CALQUENCE is a registered trademark of the AstraZeneca group of companies © 2017 AstraZeneca . All rights reserved . US-12327 11 / 17