LY-004: Phase 2, open-label, single-arm, multicenter trial of CALQUENCE monotherapy in patients (≥18 years) with MCL who had received ≥1 prior therapy (N=124)1,2
Patients received CALQUENCE 100 mg BID until disease progression or unacceptable toxicity1
Based on efficacy and safety endpoints that occurred from March 12, 2015, through approximately 14 months after the last subject was enrolled3
Independent Review Committee (IRC) and investigator assessments were conducted on primary and secondary endpoints per Lugano Classification response criteria for non-Hodgkin lymphoma (NHL)1
Based on the cumulative efficacy and safety endpoints that occurred from March 12, 2015, until data cutoff on February 12, 2018 (24-month update)3
Investigator assessments were conducted on primary and secondary endpoints per Lugano Classification response criteria for NHL3
The IRC-endpoint analyses were not conducted in the long-term data update. IRC and investigator data were highly concordant in the initial data analysis: 91.1% for overall response rate (ORR) and 93.5% for complete response (CR)3
Primary endpoint: Overall response rate (ORR) per 2014 Lugano Classification response criteria for non-Hodgkin lymphoma (NHL)1
ORR is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR)*2
Secondary endpoints: Duration of response (DoR), progression-free survival (PFS), overall survival (OS)2
Key inclusion criteria1,2
Relapsed or refractory disease, defined as achieving less than partial response with the most recent treatment
Confirmed mantle cell lymphoma with translocation t(11;14) (q13;q32), overexpressed cyclin D1, or both
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Key exclusion criteria2
Prior treatment with a BTK inhibitor
Significant cardiovascular disease†
Anticoagulation with warfarin or equivalent vitamin K antagonists
*CR (complete response) is defined as the disappearance of evidence of disease including extranodal disease (if present at baseline) and/or PET negativity based on FDG uptake less than or equal to the liver by PET-CT scan; PR (partial response) is defined as a reduction of measurable or metabolic disease and no new lesions, as defined by PET-CT scan. Efficacy endpoints were assessed by the investigator and by an Independent Review Committee.4 †Significant cardiovascular disease included uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.2
‡MIPI=Mantle Cell Lymphoma International Prognostic Index. §Alone or as part of a combination regimen.
Review characteristics that may aid in identifying potential CALQUENCE patients through a series of interactive patient profiles.
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.
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.
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, 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.
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.
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.
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.
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.
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.
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