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Calquence

Calquence Adverse Reactions

Manufacturer:

AstraZeneca

Distributor:

Zuellig
Full Prescribing Info
Adverse Reactions
The following clinically significant adverse reactions are discussed in greater detail in Precautions: Serious and Opportunistic Infections; Hemorrhage; Cytopenias; Second Primary Malignancies; Atrial Fibrillation and Flutter.
Clinical Trials Experience: As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data in Precautions reflect exposure to CALQUENCE 100 mg approximately every 12 hours in 1029 patients with hematologic malignancies. Treatment includes CALQUENCE monotherapy in 820 patients in 6 trials, and CALQUENCE with obinutuzumab in 209 patients in 2 trials. Among these recipients of CALQUENCE, 88% were exposed for at least 6 months and 79% were exposed for at least one year. In this pooled safety population, adverse reactions in ≥ 30% of 1029 patients were anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain.
Mantle Cell Lymphoma: The safety data described as follows reflect exposure to CALQUENCE (100 mg approximately every 12 hours) in 124 patients with previously treated MCL in Trial LY-004 [see Pharmacology: Pharmacodynamics: Clinical Studies: Mantle Cell Lymphoma under Actions]. The median duration of treatment with CALQUENCE was 16.6 (range: 0.1 to 26.6) months. A total of 91 (73.4%) patients were treated with CALQUENCE for ≥ 6 months and 74 (59.7%) patients were treated for ≥ 1 year.
The most common adverse reactions (≥ 20%) of any grade were anemia, thrombocytopenia, headache, neutropenia, diarrhea, fatigue, myalgia, and bruising. Grade 1 severity for the non-hematologic, most common events were as follows: headache (25%), diarrhea (16%), fatigue (20%), myalgia (15%), and bruising (19%). The most common Grade ≥ 3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea.
Dose reductions and discontinuation due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively.
Tables 6 and 7 present the frequency category of adverse reactions observed in patients with MCL treated with CALQUENCE. (See Tables 6 and 7.)

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Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.
Chronic Lymphocytic Leukemia: The safety data described as follows reflect exposure to CALQUENCE (100 mg approximately every 12 hours, with or without obinutuzumab) in 511 patients with CLL from two randomized controlled clinical trials [see Pharmacology: Pharmacodynamics: Clinical Studies: Chronic Lymphocytic Leukemia under Actions].
The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, and diarrhea.
ELEVATE-TN: The safety of CALQUENCE plus obinutuzumab (CALQUENCE+G), CALQUENCE monotherapy, and obinutuzumab plus chlorambucil (GClb) was evaluated in a randomized, multicenter, open-label, actively controlled trial in 526 patients with previously untreated CLL [see Pharmacology: Pharmacodynamics: Clinical Studies: Chronic Lymphocytic Leukemia under Actions].
Patients randomized to the CALQUENCE+G arm were treated with CALQUENCE and obinutuzumab in combination for six cycles, then with CALQUENCE as monotherapy until disease progression or unacceptable toxicity. Patients initiated obinutuzumab on Day 1 of Cycle 2, continuing for a total of 6 cycles. Patient randomized to CALQUENCE monotherapy received CALQUENCE approximately every 12 hours until disease progression or unacceptable toxicity. The trial required age ≥ 65 years of age or 18 to < 65 years of age with a total Cumulative Illness Rating Scale (CIRS) > 6 or creatinine clearance of 30 to 69 mL/min, hepatic transaminases ≤ 3 times upper limit of normal (ULN) and total bilirubin ≤ 1.5 times ULN, and allowed patients to receive antithrombotic agents other than warfarin or equivalent vitamin K antagonists.
During randomized treatment, the median duration of exposure to CALQUENCE in the CALQUENCE+G and CALQUENCE monotherapy arms was 27.7 months (range 0.3 to 40 months), with 95% and 92% and 89% and 86% of patients with at least 6 months and 12 months of exposure, respectively. In the obinutuzumab and chlorambucil arm the median number of cycles was 6 with 84% of patients receiving at least 6 cycles of obinutuzumab, 70% of patients received at least 6 cycles of chlorambucil. Eighty-five percent of patients in the CALQUENCE+G arm received at least 6 cycles of obinutuzumab.
In the CALQUENCE+G and CALQUENCE monotherapy arms, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE+G arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (2.8% to 7%).
In the CALQUENCE+G arm, adverse reactions led to treatment discontinuation in 11% of patients and a dose reduction of CALQUENCE in 7% of patients. In the CALQUENCE monotherapy arm, adverse reactions led to discontinuation in 10% and dose reduction in 4% of patients.
Tables 8 and 9 presents adverse reactions and laboratory abnormalities identified in the ELEVATE-TN trial. (See Tables 8 and 9.)

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Other clinically relevant adverse reactions (all grades incidence < 15%) in recipients of CALQUENCE (CALQUENCE in combination with obinutuzumab and monotherapy) included: Neoplasms: second primary malignancy (10%), non-melanoma skin cancer (5%).
Cardiac disorders: atrial fibrillation or flutter (3.6%), hypertension (5%).
Infection: herpesvirus infection (6%).

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Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.
ASCEND: The safety of CALQUENCE in patients with relapsed or refractory CLL was evaluated in a randomized, open-label study (ASCEND) [see Pharmacology: Pharmacodynamics: Clinical Studies: Chronic Lymphocytic Leukemia under Actions]. The trial enrolled patients with relapsed or refractory CLL after at least one prior therapy and required hepatic transaminases ≤ 2 times upper limit of normal (ULN), total bilirubin ≤ 1.5 times ULN, and an estimated creatinine clearance ≥ 30 mL/min. The trial excluded patients having an absolute neutrophil count < 500/μL, platelet count < 30,000/μL, prothrombin time or activated partial thromboplastin time > 2 times ULN, significant cardiovascular disease, or a requirement for strong CYP3A inhibitors or inducers. Patients were allowed to receive antithrombotic agents other than warfarin or equivalent vitamin K antagonist.
In ASCEND, 154 patients received CALQUENCE (100 mg approximately every 12 hours until disease progression or unacceptable toxicity), 118 received idelalisib (150 mg approximately every 12 hours until disease progression or unacceptable toxicity) with up to 8 infusions of a rituximab product, and 35 received up to 6 cycles of bendamustine and a rituximab product. The median age overall was 68 years (range: 32-90); 67% were male; 92% were White; and 88% had an ECOG performance status of 0 or 1.
In the CALQUENCE arm, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in > 5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection.
In recipients of CALQUENCE, permanent discontinuation due to an adverse reaction occurred in 10% of patients, most frequently due to second primary malignancies followed by infection. Adverse reactions led to dosage interruptions of CALQUENCE in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and dose reduction in 3.9% of patients.
Selected adverse reactions are described in Table 10 and non-hematologic laboratory abnormalities are described in Table 11. These tables reflect exposure to CALQUENCE with median duration of 15.7 months with 94% of patients on treatment for greater than 6 months and 86% of patients on treatment for greater than 12 months. The median duration of exposure to idelalisib was 11.5 months with 72% of patients on treatment for greater than 6 months and 48% of patients on treatment for greater than 12 months. Eighty-three percent of patients completed 6 cycles of bendamustine and rituximab product. (See Tables 10 and 11.)

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Other clinically relevant adverse reactions (all grades incidence < 15%) in recipients of CALQUENCE included: Skin and subcutaneous disorders: bruising (10%), rash (9%).
Neoplasms: second primary malignancy (12%), non-melanoma skin cancer (6%).
Musculoskeletal and connective tissue disorders: arthralgia (8%).
Cardiac disorders: atrial fibrillation or flutter (5%), hypertension (3.2%).
Infection: herpesvirus infection (4.5%).

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Increases in creatinine to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE.
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