Oral health is a key component of supportive care for patients with B-cell malignancies. Patients on Calquence (acalabrutinib) or Brukinsa (zanubrutinib) will require routine dental care, possible periodontal treatment, and/or tooth extraction(s) while on therapy. Both medicines are Bruton tyrosine kinase (BTK) inhibitors and have a bleeding risk associated with them. Therefore, patients on these medications will require coordinated care between the hematology/oncology team and the patient’s dentist.

Calquence is approved for the treatment of B-cell malignancies including CLL, SLL and MCL while Brukinsa is approved for the treatment of CLL/SLL and several other B-cell malignancies. Both products’ prescribing information includes warnings and precautions for hemorrhage, infections and cytopenias.

Oral health for patients on Calquence Brukinsa can be managed within the framework of their overall care, acknowledging the potential for bleeding, low blood counts, and risk of infection. Dental care can be provided as routine care or as part of the treatment for dental problems, in a manner that takes into account the patient’s current blood counts and concomitant medications, as well as the urgency and invasiveness of the dental care planned.

Why Oral Health Matters During BTK Inhibitor Therapy

In addition to inflammation, infection, trauma and bleeding of the oral cavity, local complications can arise from periodontal disease, dental caries, gingival inflammation, mucosal injury and poor fitting dental appliances.

There is a risk of bleeding in patients taking BTK inhibitors. Events of major hemorrhage or of lesser severity have been reported in patients taking Calquence Brukinsa has similar warnings for hemorrhage. Antiplatelet or anticoagulant concomitant therapy can increase the risk of bleeding for patients taking BTK inhibitors.

Therefore, even though patients with B-cell malignancies can require dental treatment, they should not be denied dental treatment for fear of hemorrhage. Instead, consideration should be given to the potential for bleeding with respect to the type of and timing of dental treatment.

Routine Dental Care and Preventive Management

Preventive oral health care will help avoid an unexpected dental crisis when patients are under treatment for their B-cell malignancies.

Regular dental examinations can help identify:

• Dental caries
• Periodontal disease
• Gingival inflammation
• Oral infections
• Broken or damaged teeth
• Mucosal abnormalities
• Problems with dental prostheses

For patients with hematologic malignancies, prevention of dental problems may be particularly important. The time when an urgent dental problem arises and requires an invasive dental treatment, may coincide with other treatment related problems and low blood counts.

Good oral hygiene, dental cleaning where appropriate and early treatment of dental disease can all form part of the routine supportive care of the patient.

Bleeding Risk Requires Individual Assessment

Importance of bleeding when dental treatment is to be done in patients on Calquence and Brukinsa.

These drugs affect BTK signaling which is involved in the activation of platelets. Data have shown that BTK inhibitors affect platelet function. This is one of the reasons for increased risk of bleeding with these drugs.

Clinical significance of bleeding risk may vary from patient to patient.

• The specific BTK inhibitor and treatment regimen
• Platelet count
• Previous bleeding events
• Concomitant anticoagulants
• Antiplatelet medicines
• Other medications affecting hemostasis
• Renal or hepatic dysfunction
• The type and extent of dental procedure
• Previous treatment history

The dental treatment cannot be considered in isolation of the patient’s hematologic and medication history.

Dental Extractions and Other Invasive Procedures

In contrast, most dental exams, dental prophylaxis and other dental treatments do not pose the same degree of risk. However, tooth extraction, periodontal surgery and other dental treatments that cause tissue damage are at higher risk of bleeding. When planning an invasive dental procedure for a patient receiving a BTK inhibitor, it is necessary to establish a management plan together with the treating hematologist or oncologist and the dental professional.

The FDA-approved prescribing information for Calquence indicates that the benefit versus risk of withholding Calquence for 3 to 7 days pre- and post-surgery should be considered on a case-by-case basis, taking into account the type of surgery to be performed and the potential for bleeding. Similarly, the prescribing information for Brukinsa indicates that consideration should be given to the benefit versus risk of withholding Brukinsa for 3 to 7 days pre- and post-surgery, based on the type of procedure to be performed and the potential for bleeding.

These recommendations do not mean that all dental work must be postponed for 3 days and then resumed. All such decisions are to be made on an individual basis by the prescribing clinician. His/her decision would be based on a consideration of the patient’s increased risk of bleeding (from his/her low platelet count) versus the increased risk of relapsing the patient’s disease (from stopping his/her oral medication for 3 days).

Platelet Counts and Other Blood Tests

Blood counts can provide useful information when planning invasive dental treatment for a patient on these medications.

Cytopenias including thrombocytopenia can occur in patients taking Calquence or Brukinsa. Complete blood counts (CBC) should be monitored regularly during treatment with these medications.

The treating team can review a patient’s recent complete blood count prior to an invasive dental treatment for a patient taking a BTK inhibitor for dental Extractions and other invasive dental Procedures. A low platelet count (thrombocytopenia) could cause an increased risk of bleeding during a dental procedure, while a low number of white blood cells (neutropenia) could cause an increased risk of developing an infection.

Lab values should be reviewed by the dental team prior to treatment, when clinically indicated.

Infection Prevention and Oral Inflammation

Infection and the BTK inhibitor: What is happening?

Brukinsa: Serious infections, including opportunistic infections, can occur in patients receiving Brukinsa. Treatment with Brukinsa and continuation of Brukinsa after a serious infection can increase the risk of serious adverse reactions. Patients receiving Brukinsa who develop serious infections should be managed according to clinical judgment and current prescribing information.

Calquence: Serious infections, including opportunistic infections, can occur in patients receiving Calquence. Treatment with Calquence and continuation of Calquence after a serious infection can increase the risk of serious adverse reactions. Patients

In addition to assessing the presence of current oral infections such as abscesses, a dental assessment for periodontal disease is indicated in the patient taking BTK inhibitors. However, it would not be appropriate to give patients on BTK inhibitors prophylactic antibiotics for dental procedures. This would depend on the individual’s degree of immunosuppression, the nature of the proposed dental treatment, the likely risk of infection, and other relevant guidelines.

Managing Concomitant Medications

Patients with different medications, and a review of these prior to dental treatment is particularly important. Patients on BTK inhibitors are often on other medications for other conditions (e.g. anticoagulation for cardiac conditions). There are warnings in the FDA labeling for both Calquence and Brukinsa for increased risk of bleeding with concomitant antithrombotic therapy.

Thus, although the BTK inhibitor may be the primary medication of concern in the cancer therapy setting, patients can also be on other medications that could interact with BTK inhibitors in clinically significant ways.

The other classes of therapy, which a patient on BTK inhibitors may also be on, have their own drug-interaction lists, for example, the list of interactions for antineoplastic drugs. In general, the main classes of interaction with BTK inhibitors are with drugs that are metabolized by the same enzymes that metabolize zanubrutinib or acalabrutinib. This is particularly relevant when antibiotics, antifungal medicines, analgesics and other medicines are being considered.

Local Hemostatic Measures

Dental procedures in patients with increased bleeding risk, local hemostatic measures can be used to achieve hemostasis.

Care must be taken to achieve hemostasis for specific dental procedures. Most dental procedures can be performed with careful tissue handling, suturing, when necessary, application of pressure and appropriate local hemostatic agents.

In general, local hemostatic measures are used for achieving hemostasis during dental procedures in antithrombotic therapy-treated patients. The dental professional must select the most appropriate local hemostatic measure for a specific dental procedure in a patient with increased bleeding risk due to BTK inhibitor therapy (Figure 5).

Recognizing Oral Bleeding and Other Warning Signs

Inform the patient of the rare case of oral bleeding to report it, persistently or unusual.

Potential warning signs may include:

• Bleeding from the gums that does not stop
• Recurrent spontaneous oral bleeding
• Blood appearing in saliva without an obvious cause
• Significant bruise around the mouth
• Persistent oral pain or swelling
• Fever associated with dental symptoms
• Signs of a dental abscess
• Difficulty swallowing or opening the mouth

The severity and persistence of symptoms determine the urgency of evaluation. Severe bleeding or a serious dental infection that requires prompt medical attention.

Coordination Between Oncology and Dental Teams

Communication between the oncology and dental teams may support coordinated patient management. Information that the dental team may need from the Oncology Team before an invasive dental procedure (IDP) includes: the patient’s diagnosis, current BTK inhibitor(s), treatment(s), blood counts, other concomitant medications, patient’s previous history of bleeding and relevant co-morbidities.

Although there are guidelines for the management of bleeding in patients with hematological malignancies who are on anticoagulation therapy, communication between the oncology team and the patient’s dental team is essential. The decision to interrupt BTK inhibitors such as Calquence and Brukinsa for a dental procedure should be made by the prescribing clinician in the oncology department on a case-by-case basis.

Interruptions in cancer treatment for unnecessary reasons can have serious consequences. However, dental treatment may be complicated by a patient’s bleeding risk. Thus, a coordinated approach between both teams of healthcare professionals is necessary to ensure both dental treatment and cancer treatment are delivered safely and effectively.

A Preventive Approach Is Often Preferable

Before an urgent care situation develops, it is preferable to find time for dental evaluation and possible treatment to make sure that you are not harboring conditions which could make a future dental treatment a real emergency.

Patients with B-cell malignancies are starting long-term BTK inhibitors. In the time before significant untreated dental problems become urgent, and require emergency dental treatment (often referred to as a dental emergency), assessment of oral health, and supply of oral care and teeth-brushing aids as required, with subsequent review by dental services, can provide a useful and acceptable preventive management approach.

There is a view that necessary dental treatment should be postponed indefinitely because a patient is receiving a BTK inhibitor for their cancer. However, such treatment could be contraindicated and in others there would be a need for treatment with consideration of the cancer and its treatment.

Briefly

Managing a patient’s oral health is an important part of their supportive or palliative care when they are in treatment with Calquence or Brukinsa. Both acalabrutinib and zanubrutinib can increase a patient’s risk of bleeding and have the potential to cause a number of different cytopenias (reductions in blood cell counts) and increase a patient’s risk of infections.

Preventive dental care may help reduce the likelihood of urgent dental complications. However, there are occasions when an invasive dental procedure is required. These procedures may be performed following individualized clinical assessment, including review of blood counts and bleeding risk, with a complete list of medications that the patient is taking, and with consideration of the proposed dental treatment and associated risks of bleeding and of infection.

Treatment of BTK inhibitors can be interrupted for invasive dental procedures as needed, under the care of the prescribing clinician. Each case can be looked at individually to assess the best course of action for each patient’s specific situation, taking into consideration their recent lab values, current treatment, and upcoming dental work.

Disclaimer: The information provided in this article is intended for educational purposes only and should not be interpreted as medical advice, a clinical guideline, or a recommendation for any specific treatment.

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