NCCN Guidelines® recommend acalabrutinib (CALQUENCE) as a second-line therapy option for MCL (Category 2A).
Suggested treatment regimens for second-line therapy for mantle cell lymphoma (MCL)*†1
SHORT RESPONSE DURATION TO PRIOR CHEMOIMMUNOTHERAPY (< EXPECTED MEDIAN PFS)
Preferred regimens (in alphabetical order)
Other recommended regimen
Consider prophylaxis for tumor lysis system (See NHODG-B) See monoclonal antibody and viral reactivation (NHODG-B)
EXTENDED RESPONSE DURATION TO PRIOR CHEMOIMMUNOTHERAPY (> EXPECTED MEDIAN PFS)
Preferred regimens (in alphabetical order)
Other recommended regimens (in alphabetical order by category)
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® Recommendations) for B-Cell Lymphomas V.4.2018. © 2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® Recommendations and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines Recommendations, go online to NCCN.org. The NCCN Guidelines Recommendations are a work in progress that may be redefined as often as new significant data become available.
*All recommendations in the B-cell lymphoma guidelines are category 2A unless otherwise noted. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
†Rituximab and hyaluronidase human injection for subcutaneous use may be substituted for rituximab after patients have received the first full dose of rituximab by intravenous infusion. This substitution cannot be made for rituximab used in combination with ibritumomab tiuxetan.
‡The Phase 2 ACE-LY-004 study excluded patients treated with BTK or BCL-2 inhibitors and concomitant warfarin or equivalent vitamin K antagonists.
§Special considerations for the use of the small-molecule inhibitor, acalabrutinib, include the following:
||For special considerations concerning ibrutinib, please see pages NHODG-E 2 of 3 and 3 of 3. 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.
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.
Please see complete Prescribing Information including Patient Information.
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