INDICATIONS AND USAGE

CALQUENCE is indicated in combination with bendamustine and rituximab (BR) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT) and as monotherapy for the treatment of adult patients with MCL who have received at least one prior therapy.

SELECT SAFETY INFORMATION

Serious adverse events, including fatal events, have occurred with CALQUENCE, including serious and opportunistic infections, hemorrhage, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity, including drug-induced liver injury. The most common adverse reactions (≥30%) are upper respiratory tract infection, diarrhea, headache, and musculoskeletal pain. The most common Grade 3 or 4 laboratory abnormalities (≥10%) are absolute neutrophil count decreased, uric acid increased, absolute lymphocyte count decreased, and platelets decreased.

Please see full Important Safety Information at the end of the video. Please see full Prescribing Information, including Patient Information.

Hello, my name is Doctor Tycel Phillips. I'm an associate professor at City of Hope National Medical Center located in Duarte, California. I've been practicing for the last 12 years in the management and treatment of patients with malignant B-cell lymphoproliferative disorders.

In this video, we will be discussing the 3-year median follow-up data from the LY-004 trial of CALQUENCE in patients with relapsed/refractory mantle cell lymphoma. When I look at follow-up study data for patients with relapsed/refractory mantle cell lymphoma, I ask myself, are the safety and efficacy data at long-term follow-up consistent with the initial analysis? Are safety and tolerability data consistent with the established safety profile? What endpoints are most relevant to helping my patients achieve treatment goals?

LY-004 is one of the largest clinical trials in relapsed or refractory mantle cell lymphoma. LY-004 was a Phase 2, open-label, single-arm, multicenter trial of CALQUENCE monotherapy in 124 patients aged 18 or older with mantle cell lymphoma, who had received at least one prior line of therapy.

The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints included duration of response (DoR).

The initial analysis had a median follow-up of 15.2 months. The long-term analysis had a median follow-up of 38.1 months.

Now, let's take a look at the efficacy data.

The response rate of CALQUENCE was consistent in patients with relapsed or refractory mantle cell lymphoma and has continued to show deep responses over time. In the initial analysis at a median follow-up of 15.2 months, CALQUENCE demonstrated an IRC-assessed overall response rate of 80%: complete response rate of 40%, and partial response rate of 40%. In the long-term analysis, with a median follow-up of 38.1 months, CALQUENCE has continued to show deep responses, with 48% of patients having a complete response. Overall response rate was 81% and partial response rate was 34%.

Duration of response was measured in the 101 patients who achieved a complete response or partial response at the 38-month median follow-up. The median duration of response was around 29 months.

The most important aspect of the LY-004 data, which helps as far as making decisions for treatment for patients with relapsed/refractory mantle cell lymphoma, is efficacy and duration of response data. This calls to mind a patient who was recently started on CALQUENCE. Unfortunately, this patient had a very short duration of response to frontline chemoimmunotherapy. The patient was subsequently started on CALQUENCE and was noted to being in a complete response at first interim assessment after 3 months of therapy. Now, let's take a look at the safety data from the trial.

In the long-term analysis, with a median follow-up of 38.1 months, the safety profile of CALQUENCE was consistent with the initial analysis. The most common treatment-emergent adverse events occurring in greater than or equal to 20% of patients were infections, headache, diarrhea, bleeding events, fatigue, cough, myalgia, and nausea.

CALQUENCE has demonstrated low rates of atrial fibrillation and hypertension in the LY-004 study. At the long-term analysis, with a median follow-up of 38.1 months, atrial fibrillation was 1.6% for all grades and 0% for Grade 3 or higher, and hypertension was 4% for all grades and 1.6% for Grade 3 or higher. At the interim analysis, with a median follow-up of 15.2 months, atrial fibrillation was 0% for all grades or Grade 3 or higher, and hypertension was 2.4% for all grades and 0.8% for Grade 3 or higher.

These data are consistent with what I see in my clinical practice. Safety continues to be an important aspect of any continuous therapy. The long-term data from LY-004 continues to support the safety of CALQUENCE in patients with relapsed/refractory mantle cell lymphoma. The adverse reactions noted are all generally managed with the assistance of the healthcare team.

Few patients discontinued therapy due to adverse reactions. In the initial analysis, dose reductions due to adverse reactions were reported in 1.6% of patients, and 6.5% of patients discontinued therapy due to adverse reactions. Median duration of therapy was 16.6 months, with a range of 0.1 to 26.6 months. At the 38-month median follow-up, dose reductions due to adverse events were reported in 2% of patients, and 11% of patients discontinued therapy due to adverse events.

In LY-004, 8 out of 10 patients with relapsed/refractory mantle cell lymphoma responded to CALQUENCE, with a 29-month duration of response at the 38-month median follow-up. At a median follow-up of 15.2 months, the most common adverse reactions occurring in greater than or equal to 20% of patients with CALQUENCE were anemia, thrombocytopenia, headache, neutropenia, diarrhea, fatigue, myalgia, and bruising. The safety profile remained consistent over time as demonstrated in the initial analysis and observed with the 38-month data, including low rates of atrial fibrillation and hypertension.

The 3-year follow-up data from the LY-004 study is consistent with what I see in my clinical practice. Thanks for watching. Stay tuned for full Important Safety Information for CALQUENCE.

INDICATIONS AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated in combination with bendamustine and rituximab (BR) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT) and as monotherapy for the treatment of adult patients with MCL who have received at least one prior therapy.

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE^® (acalabrutinib) tablets

Serious and Opportunistic Infections

Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 29% of 2,055 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (18% of all patients, including pneumonia in 14%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 8% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 4.7% of patients, with fatal hemorrhage occurring in 0.1% of 2,055 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 39% of patients. Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 5% of patients taking CALQUENCE without antithrombotic agents and 3.2% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients 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.

Cytopenias

CALQUENCE can cause Grade 3 or 4 cytopenias. Grade 3 or 4 cytopenias included absolute neutrophil count decreased (28%), absolute lymphocyte count decreased (10%), hemoglobin decreased (9%), and platelets decreased (9%) in 1,758 patients treated with CALQUENCE alone and in combination with obinutuzumab or venetoclax; Grade 4 neutropenia developed in 14% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies

Second primary malignancies, including skin cancers and other solid tumors, occurred in 16% of 2,055 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 9% of patients, followed by other solid tumors in 8% (including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers) and hematologic malignancies (1.1%). Fatal second primary malignancies occurred in 0.8% of patients. Monitor patients for the development of second cancers and advise protection from sun exposure.

Cardiac Arrhythmias

Fatal and serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. Grade 3 or 4 atrial fibrillation or flutter was reported in 2.2% of 2,055 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 7% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.5% of patients, including fatal cases in 0.3% of all patients. The risk of arrhythmias may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including CALQUENCE. Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE.

ADVERSE REACTIONS

Previously Untreated Mantle Cell Lymphoma

The most common adverse reactions (≥15%) of any grade in patients with previously untreated MCL in the ECHO study who received CALQUENCE plus BR (n=297) were rash (47%), COVID-19 (38%), fatigue (37%), diarrhea (37%), pneumonia (31%), headache (31%), upper respiratory tract infection (30%), pyrexia (29%), cough (27%), vomiting (26%), constipation (25%), hemorrhage (20%), edema (20%), secondary primary malignancy (19%), dizziness (18%), arthralgia (18%), and dyspnea (17%). Grade 4 laboratory abnormalities in >15% of patients treated with CALQUENCE plus BR include absolute lymphocyte count decreased (26%), absolute neutrophil count decreased (36%), and uric acid increased (17%).

Serious adverse reactions occurred in 69% of patients who received CALQUENCE plus BR. Serious adverse reactions reported in ≥2% of patients were pneumonia (23%; includes COVID-19 pneumonia), COVID-19 (20%; includes COVID-19 pneumonia), second primary malignancy (7%), pyrexia (6%), rash (3.4%), febrile neutropenia (3.4%), atrial fibrillation (3%), sepsis (2.7%), and anemia (2.4%). Fatal adverse reactions that occurred within 30 days of the last study treatment were reported in 12% who received CALQUENCE plus BR including COVID-19 (6%; includes COVID-19 pneumonia), pneumonia (1%), second primary malignancy (0.7%), sepsis (0.3%), and pneumonitis (0.3%).

Adverse reactions led to permanent discontinuation of CALQUENCE in 43%, dosage interruptions in 74%, and dosage reductions in 10% of patients. Adverse reactions that resulted in dosage modification in >10% included infections, cytopenias, rashes, and gastrointestinal toxicity. Adverse reactions which resulted in permanent discontinuation of CALQUENCE in ≥4% of patients included COVID-19 (includes COVID-19 pneumonia) and neutropenia.

Previously Treated Mantle Cell Lymphoma

The most common adverse reactions (≥20%) of any grade in patients with relapsed or refractory MCL in the LY-004 study exposed to CALQUENCE (n=124) were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%).

*Treatment-emergent decreases (all grades) of hemoglobin (46%), platelets (44%), and neutrophils (36%) were based on laboratory measurements and adverse reactions.

Dose reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively. Increases in creatinine to 1.5 to 3 times the upper limit of normal (ULN) occurred in 4.8% of patients.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.

Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.

SPECIFIC POPULATIONS

Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for 1 week following the last dose of CALQUENCE. It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for 2 weeks after the last dose. Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Please see full Prescribing Information, including Patient Information.