Appropriate treatment for MCL varies by patient1-4

  • MCL can manifest with a clinically variable profile, with most cases presenting at an advanced stage at diagnosis2-4

  • Although MCL is frequently diagnosed at an advanced stage in elderly males, each patient has a unique disease profile

Mantle Cell Lymphoma treatment decision guidelines Mantle Cell Lymphoma treatment decision guidelines

Disease variability may also play a role in treatment selection3,5

Factors predictive of disease course in MCL patients5

Factors predictive of disease course in mantle cell lymphoma (MCL) patients Factors predictive of disease course in mantle cell lymphoma (MCL) patients

The treatment of relapsed/refractory MCL is evolving6-8

Although treatment options exist, there is no consensus on a standard therapy for relapsed/refractory MCL6,9

Relapsed/Refractory Mantle Cell Lymphoma treatment options Relapsed/Refractory Mantle Cell Lymphoma treatment options

BTK inhibitors are important to the treatment of B-cell malignancies such as MCL2,7,8

BTK is instrumental in the10:

  • Proliferation and survival of B-cell malignancies

  • Retention of malignant cells in lymphoid tissue

The pharmacologic properties of kinase inhibitors can vary The pharmacologic properties of kinase inhibitors can vary

NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY (NCCN GUIDELINES® RECOMMENDATIONS) STATE THAT ACALABRUTINIB IS A SECOND-LINE THERAPY OPTION FOR MCL (CATEGORY 2A)*9

Learn more about the NCCN Guidelines® Recommendations for the treatment of relapsed/refractory MCL.

*The Phase 2 ACE-LY-004 study excluded patients treated with BTK or BCL-2 inhibitors, and concomitant warfarin or equivalent vitamin K antagonists.7,14

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

 

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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.

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 may report side effects related to AstraZeneca products by clicking here.

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Reference:

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

References:

  1. Dreyling M, Aurer I, Cortelazzo S, et al. Treatment for patients with relapsed/refractory mantle cell lymphoma: European-based recommendations. Leuk Lymphoma. 2018;59(8):1814-1828.
  2. Sandoval-Sus JD, Sotomayor EM, Shah BD. Mantle cell lymphoma: contemporary diagnostic and treatment perspectives in the age of personalized medicine. Hematol Oncol Stem Cell Ther. 2017;10(3):99-115.
  3. Shah BD, Martin P, Sotomayor EM. Mantle cell lymphoma: a clinically heterogeneous disease in need of tailored approaches. Cancer Control. 2012;19(3):227-235.
  4. Parrott M, Rule S, Kelleher M, Wilson J. A systemic review of treatments of relapsed/refractory mantle cell lymphoma. Clin Lymphoma Myeloma Leuk. 2018;18(1):13-25.
  5. Cohen JB, Zain JM, Kahl BS. Current approaches to mantle cell lymphoma: diagnosis, prognosis, and therapies. Am Soc Clin Oncol Educ Book. 2017;37:512-525.
  6. Cheah CY, Seymour JF, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34:1256-1269.
  7. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  8. Dreyling M, Ferrero S; on behalf of European Mantle Cell Lymphoma Network. The role of targeted treatment in mantle cell lymphoma: is transplant dead or alive? Haematologica. 2016;101(2):104-114.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed May 17, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.
  10. Pal Singh S, Dammeijer F, Hendriks RW. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol Cancer. 2018;17(1):57.
  11. Barf T, Covey T, Izumi R, et al. Acalabrutinib (ACP-196): A covalent bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. J Pharmacol Exp Ther. 2017;363(2):240-252.
  12. Barf T, Kaptein A. Irreversible protein kinase inhibitors: balancing the benefits and risks. J Med Chem. 2012;55(14):6243-6262.
  13. Paweletz CP, Andersen JN, Pollock R, et al. Identification of direct target engagement biomarkers for kinase-targeted therapeutics. PLoS One. 2011;6(10):e26459.
  14. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

Reference:

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed May 17, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Hendriks RW, Yuvaraj S, Kil LP. Targeting Bruton’s tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014;14(4):219-232.
  3. Barf T, Covey T, Izumi R, et al. Acalabrutinib (ACP-196): A covalent Bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. J Pharmacol Exp Ther. 2017;363(2):240-252.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Data on File, REF-33702, AstraZeneca Pharmaceuticals LP.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Data on File, REF-43179. AstraZeneca Pharmaceuticals LP.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Data on File, REF-43179. AstraZeneca Pharmaceuticals LP.
  4. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano Classification. J Clin Oncol. 2014;32:3059-3068.
  5. Data on File, REF-18540. AstraZeneca Pharmaceuticals LP.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano Classification. J Clin Oncol. 2014;32:3059-3068.
  4. Data on File, REF-43179. AstraZeneca Pharmaceuticals LP.

References:

  1. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  2. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  3. Data on File, REF-43179, AstraZeneca Pharmaceuticals LP.

Reference:

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