Helping General Oncologists Make CLL Treatment Decisions
Key Findings
- Targeted agents have replaced chemoimmunotherapy for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)
- Despite national guidelines and data that support the improved effectiveness and safety of novel agents, too many patients do not receive them
- Decisions about treatment selection and sequencing can be complex, which may be a barrier
- A new document consolidates the data and offers recommendations and algorithms to help guide treatment decisions
Subscribe to the latest updates from Cancer Center Advances in Motion
A Massachusetts General Hospital oncologist, Jacob Soumerai, MD, is leading an effort to ensure that all patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) receive the most up-to-date and effective treatments for the disease. He recently chaired a Lymphoma Research Foundation (LRF) panel that developed comprehensive guidelines to help other healthcare providers navigate these complex treatment decisions.
"Over the past decade or so, we've seen dramatic improvements in treatment options available for our patients with CLL. Where we previously used traditional chemotherapies, we no longer recommend chemotherapy in CLL, given the development of safer and more effective biologically targeted therapies," said Dr. Soumerai. "It can be difficult to wade through all of the data and sort out what the best treatment option is for each individual patient and at each line of therapy."
He and a group of other CLL/SLL experts from throughout the United States recently created a comprehensive and highly practical guideline paper that healthcare providers can use to identify individual patient factors that should inform treatment decisions. The "Consensus Recommendations from the 2024 Lymphoma Research Foundation Workshop on Treatment Selection and Sequencing in CLL or SLL" is now published in Blood Advances.
Novel Treatment Options for CLL/SLL
Recent advancements have dramatically changed the treatment paradigm for patients with CLL/SLL from traditional chemoimmunotherapy to novel targeted therapies. Examples include:
- Next-generation Bruton tyrosine kinase (BTK) inhibitors such as acalabrutinib, zanubrutinib, and pirtobrutinib
- B-cell lymphoma 2 (BCL-2) inhibitors such as venetoclax
- Next-generation monoclonal antibody therapies such as obinutuzumab
- Cellular immune therapies such as CAR T-cell therapy lisocabtagene maraleucel
Studies have shown that novel agents are not only safer than traditional chemotherapy but also provide superior efficacy outcomes, including longer remissions, progression-free survival, and in some cases overall survival. Therefore, these therapies are the center of national guidelines and recommendations for CLL/SLL treatment.
Bridging the Gap Between National Guidelines and Real-World Practice
However, there is a gap between the evidence-based guidelines and real-world practice.
"We've seen a significant reduction in the use of traditional chemotherapy, but we still see patients who are receiving them — as many as 1 in 6 patients nationally — despite existing guidelines and recommendations," Dr. Soumerai said.
He believes this gap exists for two main reasons. First, decisions regarding the selection and sequencing of these novel therapies is increasingly complex. Second, healthcare providers treating this patient population may not have the resources to wade through rapidly evolving data to determine the best treatment option for the patient in front of them.
"While most oncologists are using novel targeted agents, they need better tools to navigate the complex decisions about which treatment to choose for frontline treatment, and at subsequent lines of therapy," he said.
Experts Offer Recommendations and Tools to Guide Complex Decisions
The LRF convened a panel of CLL/SLL experts to help consolidate and simplify the process. The resulting document consolidates the data and provides consensus recommendations about how to make first-, second-, and third-line decisions and beyond.
The document also offers tools such as decision-making algorithms that take into account several patient-specific factors, such as:
- Symptoms and complications related to the CLL
- Other comorbidities and concomitant medications
- Results of genetic sequencing (for example, immunoglobulin heavy-chain variable region gene [IGHV] status, del(17p)/TP53 mutation status)
- Results of novel molecular tests, such as measurable residual disease (MRD)
- Patient preferences
- Potential side effects or late effects of treatments
"Often, these factors may sway you in different directions, but this can quickly become very complicated. So when you are seeing a patient with CLL, this consensus document provides clear guidance on how to assess these factors and how to think about which factors should drive your decision-making for an individual patient with CLL," he said. "This is very comprehensive, and can be applied to and inform the care of any patient with CLL/SLL at all decision points in their care."
Evolving With the Changing Landscape of CLL/SLL Treatment
The field of CLL/SLL continues to evolve, with new treatments being developed and approved at a rapid pace. Examples over the past year alone include a new BTK inhibitor called pirtobrutinib and a chimeric antigen receptor (CAR) T-cell therapy called lisocabtagene maraleucel.
Dr. Soumerai said the recommendations are designed to evolve alongside these developments. The algorithms are designed to adapt as new therapeutic options become part of the decision-making process. In addition, the LRF plans to regularly reconvene a working group to incorporate new treatment options and data.
In the meantime, the LRF also developed resources for patients related to the panel's work, which will soon be made available to patients.
"We need to encourage providers to engage their patients in treatment selection discussions, and also to educate patients on the treatment landscape and factors influencing treatment selection and sequencing," Dr. Soumerai said. "This will empower patients to voice their preferences, and facilitate more personalized treatment recommendations."