Imaging has an important but disease-specific role in the assessment of patients with B-cell malignancies treated with targeted therapies. Therefore, for the clinician managing patients with chronic lymphoid B-cell malignancies, including chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), and other diseases, information from imaging studies can be very relevant.

Calquence (acalabrutinib) and Brukinsa (zanubrutinib) are Bruton tyrosine kinase (BTK) inhibitors. Calquence is approved for CLL/SLL and MCL. Brukinsa is approved for CLL/SLL and also for other B-cell malignancies including WM, MZL and FL. However, imaging should not be viewed in isolation from other information such as physical examination findings and from laboratory results. In addition, the modality chosen, the time of imaging and how images are to be interpreted will all depend on a variety of factors, including the type of disease, the intent of therapy, the patient’s pretreatment disease, clinical situation and the specific criteria by which treatment response is to be assessed.

The Role of Imaging in B-Cell Malignancies

Imaging can be used to assess disease at sites that have not been fully assessed by physical examination or by laboratory tests. Imaging can be performed using CT, PET/CT, MRI and/or ultrasound, depending on the specific clinical scenario.

For CLL, routine imaging with CT is not recommended for staging or for routine assessment of patients. The iwCLL guidelines (Haberman et al., Leukemia 2016) that are used for assessment of many patients with CLL recommend physical examination and blood counts for routine assessment of patients. CT scans are used in selected cases.

The distinction between normal or stable findings on imaging studies and those indicative of progression must be kept in mind. Changes in patients undergoing targeted therapy for their cancer can be indistinguishable from those of patients with refractory disease and, therefore, are not in themselves determinative of treatment failure.

Imaging in CLL and SLL

CLL and SLL are two related diseases. Patients with CLL have abnormally growing lymphocytes in the blood, whereas patients with SLL have abnormal lymphocytes growing in lymph nodes, spleen, and sometimes in the blood.

However for patients with CLL a physical examination and blood counts form the basis for assessment of CLL. A CT of neck, chest, abdomen and pelvis can be performed in select cases where patients present with clinically significant lymphadenopathy and assessment with imaging is required in the context of a clinical trial for response assessment.

Comparative imaging is critical and will often be against appropriate prior studies, assessment of change in size and numbers of involved lymph nodes as well as involvement of spleen and other organ sites. Single measurements of involved nodes will often be insufficient to make accurate clinical assessments.

Calquence and Imaging Considerations

Calquence is the brand name for the drug acalabrutinib, a BTK inhibitor approved for adults with CLL or SLL, and for adults with mantle cell lymphoma. By blocking the BTK enzyme, acalabrutinib, or Calquence, as it’s referred to on the market, prevents B-cells from receiving signals from their surface B-cell receptors and ultimately results in B-cell death. Its actions differ from typical chemotherapy, therefore, the treatment’s effects on disease and on the body of the patient differ from typical chemotherapies.

For clinicians treating patients on study or on maintenance therapy with novel inhibitors, changes in lymph node size may be considered as part of response assessment when interpreted alongside clinical and laboratory findings and hence clinicians must consider all findings to conclude on treatment response. These radiographic findings, therefore, need to be looked at within the framework of entire clinical findings and all lab results. In addition, there are instances when a transient increase in size of lymph nodes can occur even when patient is on therapy. This increase needs to be ruled out as progression of disease. In CLL/SLL, a single measurement of size of lymph node is not a good marker for change therefore measurement in same patients over time in comparison to measurements taken prior to start of therapy and in conjunction with findings on physical examination as well as lab findings to determine assessment of response on therapy.

Innovative agents may result in transient increases in lymph node size during treatment and CLL guidelines state that these increases should not be considered as disease progression. This is an important consideration when trying to make sense of early images taken of patients on BTK inhibitor therapy.

Brukinsa and Imaging Considerations

Zanubrutinib (Brukinsa) was approved by the FDA for the treatment of CLL/SLL and for other B-cell malignancies including mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, and follicular lymphoma.

Zanubrutinib is used in many different diseases. In many of these, Brukinsa is used in combination with other therapies, as well as for therapy of different stages or intents of the individual’s disease. Thus, assessment for Brukinsa must be considered in the specific context of the individual’s disease and treatment objectives.

For example, a patient with CLL/SLL on zanubrutinib would typically need imaging to assess response in a different manner than a patient with lymphoma on the same drug who would be assessed for response using FDG-PET/CT as part of standard response assessment. Importantly, imaging requirements are determined more by the underlying disease (e.g. CLL/SLL vs. lymphoma) and corresponding objectives of treatment rather than by specific drugs used for treatment.

CT Remains Important in Selected Settings

CT scans are typically used to take pictures of the inside of the body and determine the size of lymph nodes and other organs and to determine if there is any involvement of vital organs (such as the liver, spleen, etc).

In CLL, routine follow-up of patients does not require repeated CT scans. According to the iwCLL guidelines, routine follow-up of patients with CLL does not require repeated CT scans for assessment of disease as progression or relapse is often detected by clinical examination and blood counts. In clinical trials, it may be useful to obtain a baseline CT scan and a follow-up scan at a specific time after initiation of treatment to assess response. There is little value in obtaining multiple CT scans between clinically meaningful assessment time points, since these additional scans provide little useful information and expose patients to unnecessary radiation.

In terms of imaging follow-up in patients under long-term BTK-inhibitor treatment for CLL, the distinction between ‘regular’ assessment and ‘response-assessment’ is crucial for determining the optimal number of scans.

PET/CT Has a More Selective Role in CLL

FDG-PET/CT is not routinely used to monitor uncomplicated CLL. PET/CT has a very limited role in monitoring CLL patients. One exception is suspected transformation to a more aggressive lymphoma (Richter’s syndrome). Here, the metabolically active tumors can be localized by the PET/CT scan and a biopsy can be performed in the selected lymph node or in the tissue (e.g. from a lymph node biopsy).

FDG-PET/CT can be very useful in determining the sites of possible biopsies in suspected cases of Richter transformation. This would include cases where there are rapidly enlarging lymph nodes and/or other clinical findings that are indicative of CLL-related symptoms in addition to unexplained symptoms that are indicative of possible lymphoma. For suspected Richter transformation (Richter’s), PET/CT can be used to help select a lymph node or other tissue for a biopsy. Imaging does not replace a tissue diagnosis in such cases.

Imaging Findings Should Be Interpreted With Clinical Data

Imaging should be used in conjunction with the patient’s clinical findings when they are on treatment with Calquence or Brukinsa.

Relevant information may include:

• Physical examination findings
• Complete blood count and differential
• Lymph node measurements
• Spleen and liver findings
• Disease-related symptoms
• Treatment history
• Genetic and molecular characteristics
• Previous imaging findings
• Treatment duration
• Potential treatment-related complications

A description of different parameters is used to assess progressive disease in CLL patients. Newly appearing or enlarging of single or multiple lymph nodes, increase in size of spleen or liver or worsening of blood counts such as reduction of platelets or increase in white blood cell count are some of the parameters. A diagnosis of progressive disease can be made if any of the above parameters are present and confirmed by repeat imaging in combination with clinical assessment.

Avoiding Misinterpretation of Early Imaging Changes

Targeted therapies may produce response patterns that require proper clinical assessment. A temporary increase in the size of lymph nodes that return to normal size after several weeks is commonly seen under treatment with novel BTK-inhibitors (e.g. Calquence). These increases in size are not considered as signs of progressive disease according to the iwCLL criteria.

It is crucial to compare the new findings on the current images with the prior study(s). A single finding of an increase in size of a lymph node(s) may need to be correlated with the patient’s current clinical status including blood counts, symptomatology, physical examination, and subsequent clinical follow-up prior to any consideration of a change in treatment.

Imaging and Long-Term Treatment Monitoring

Patients on oral BTK inhibitors are on treatment for an extended period of time depending on the individual case (disease, treatment concept, response, tolerability etc.). Monitoring patients under long-term treatment with oral BTK inhibitors for B-cell malignancies requires a balance between monitoring with potential value by imaging and the limitations of said imaging. Repeated CT-examinations under routine circumstances are not required for every single CLL patient.

On the other hand, new symptoms or physical findings will necessitate further evaluation by imaging. For example, new or rapidly enlarging lymphadenopathy, unexplained symptoms of illness (e.g. fever), and transformation to an aggressive lymphoma (e.g. dendritic cell lymphoma) would warrant further investigation by appropriate imaging. The objective of the use of imaging in patients with CLL is to obtain appropriate information, and not to perform more imaging studies.

A Disease-Specific Approach Remains Essential

The use of Calquence Brukinsa for a number of different B-cell malignancies means that a single imaging protocol for the treatment of these diseases would not be appropriate.

CLL/SLL, mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma and other B-cell malignancies are a heterogeneous group of diseases with different biological features and with different criteria for the assessment of response to treatment.

Physical examination and blood counts are crucial for the assessment of CLL/SLL patients. CT scans are of selective value. For other B-cell malignancies, like mantle cell lymphoma, marginal zone lymphoma or follicular lymphoma, even for the same BTK-inhibitors, PET/CT is of much greater value for the assessment of response.

Final Thoughts

Imaging can play a role in monitoring patients with B-cell malignancies during treatment, but this will differ from one disease to another. For patients on Calquence or Brukinsa, imaging findings should be compared to the patients’ physical examination, lab values, symptoms, and treatment history. In the case of CLL, repeated CT scans are not typically required for long-term treatment but may be required for assessment of clinical trial endpoints. In certain situations, CT scans may be required for assessment of individual patients. PET/CT scans may be required for assessment of suspected Richter transformation.

Imaging needs to be used to answer specific questions. With a disease-specific response criteria driven approach, the clinician can distinguish between true disease progression and other causes of imaging changes that are related to treatment. This allows for an informed clinical decision with regards to further management.

Related posts:

Other Imaging Techniques in Dilated Cardiomyopathy Basic Echocardiography in Arrhythmogenic Right Ventricular Cardiomyopathy How Often Do You Really Need Dental X-Rays? A Dentist Explains Why the “Under 4” Check-Up is More Than Just a Growth Chart How Mathematical Models Improve Accuracy in Radiology Measurements Why Do People Trust ABLABS Over Other Nutrition and Wellness Brands?

Stay updated, free articles. Join our Telegram channel

Join