About Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a rare type of B-cell non-Hodgkin lymphoma.2-4

MCL is typically diagnosed at an advanced stage and in older individuals4:

  • Approximately 3,300 new cases of MCL are diagnosed in the US each year5

  • Most patients are diagnosed at an advanced stage (Stage III or IV)4

  • Mean age at diagnosis is 684

  • Occurs more than twice as often in men than women4

Incidence rate for men is more than twice that for women.Incidence rate for men is more than twice that for women.

While MCL initially responds to treatment, it has a high relapse rate.2

Most patients are classified as intermediate- or high-risk based on MIPI, a validated prognostic indicator for MCL*3

5-Year Overall Survival Based on MIPI Risk5-Year Overall Survival Based on MIPI Risk

*MIPI=Mantle Cell Lymphoma International Prognostic Index. The MIPI score is based on a calculation that incorporates multiple factors, including age, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase activity, and white blood cell count. Patients with MIPI score <5.70 are classified as low risk, patients with MIPI score ≥5.70 but <6.20 as intermediate risk, and patients with MIPI score ≥6.20 as high risk.3

There is no standard therapy for relapsed/refractory MCL.2,6

Treatment options include chemoimmunotherapy, stem cell transplant, targeted therapy, and experimental agents in clinical trials.2,6

MCL is incurable, and patients who relapse or are refractory to treatment have a poor prognosis.3

What is CALQUENCE® (acalabrutinib)?

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.

CALQUENCE Mechanism of Action1,7

Preclinical studies demonstrated that CALQUENCE is a small-molecule Bruton tyrosine kinase (BTK) inhibitor.1

BTK plays a key role in B-cell receptor signaling.

CALQUENCE binds irreversibly to BTK, thereby inhibiting its activity.1,7

BTK plays a key role in B-cell receptor signaling.BTK plays a key role in B-cell receptor signaling.

CALQUENCE is a small-molecule inhibitor of BTK1

In nonclinical studies, acalabrutinib inhibited BTK-mediated activation of downstream signaling proteins CD86 and CD69 and inhibited malignant B-cell proliferation and survival.1

+

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 discontinuation 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.

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.

Please see complete Prescribing Information including Patient Information.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Back to top

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Cheah CY, Seymour JF, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34:1256-1269.
  3. Hoster E, Klapper W, Hermine O, et al. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol. 2014;32:1338-1346.
  4. Zhou Y, Wang H, Fang W, et al. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer. 2008;113:791-798.
  5. Teras LR, DeSantis CE, Cerhan JR, et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016;66:443-459.
  6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). B-cell lymphomas. Version 3.2017. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf.Accessed June 28, 2017.
  7. Hendriks RW, Yuvaraj S, Kil LP. Targeting Bruton’s tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014;14(4):219-232.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Data on File, 18540, AstraZeneca Pharmaceuticals LP.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Data on File, 18540, AstraZeneca Pharmaceuticals LP.

Reference:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.