What is the treatment for Chronic Lymphocytic Leukemia (CLL)?

From the Guidelines

The treatment of chronic lymphocytic leukemia (CLL) should be based on disease stage, presence or absence of del(17p) or TP53 mutation, IGHV mutation status, patient age, performance status, and comorbid conditions, with targeted therapy with BTKi and venetoclax being the preferred first-line treatment for all patients with CLL. When considering treatment options, the following factors should be taken into account:

• Disease stage: early-stage asymptomatic patients can be monitored with regular check-ups, while those with advanced disease or symptoms require immediate treatment 1.
• Genetic markers: del(17p) or TP53 mutation status, and IGHV mutation status can guide treatment selection 1.
• Patient factors: age, performance status, and comorbidities should be considered when choosing a treatment regimen 1. Some key treatment options include:
• BTK inhibitors like ibrutinib, acalabrutinib, or zanubrutinib, which are effective for first-line treatment of CLL 1.
• Venetoclax plus obinutuzumab, which is a suitable option for older patients or those with comorbidities 1.
• Chemoimmunotherapy combinations like FCR, which may be used in younger, fit patients with favorable genetics 1. It is essential to monitor patients for adverse events and provide supportive care for treatment-related complications, as side effect management is crucial in CLL treatment 1. Treatment selection and management should be individualized, taking into account the patient's specific needs and circumstances, and guided by the most recent and highest-quality evidence, such as the NCCN clinical practice guidelines in oncology 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Chronic Lymphocytic Leukemia (CLL) BENDEKA® is indicated for the treatment of patients with chronic lymphocytic leukemia. Efficacy relative to first line therapies other than chlorambucil has not been established.

• Treatment options for chronic lymphocytic leukemia (CLL) include:
  • Bendamustine (IV) 2
  • Rituximab (IV) in combination with fludarabine and cyclophosphamide (FC) for adult patients with previously untreated and previously treated CD20-positive CLL 3
• Key points:
  • Bendamustine is indicated for the treatment of patients with CLL.
  • Rituximab is indicated for the treatment of adult patients with CD20-positive CLL in combination with FC.

From the Research

Treatment Options for Chronic Lymphocytic Leukemia

• The standard approach for treating chronic lymphocytic leukemia (CLL) is a "watch and wait" strategy, unless "active disease" criteria are met 4.
• First-line treatment typically consists of a combination of CD20 antibody (rituximab, ofatumumab, or obinutuzumab) and chemotherapy (fludarabine/cyclophosphamide, bendamustine, chlorambucil) 4.
• For patients with 17p deletion or TP53 mutation, novel agents such as signaling kinase inhibitors (e.g., ibrutinib) and BCL2 antagonists (e.g., venetoclax) have shown dramatic efficacy 4.

Efficacy of Specific Treatment Regimens

• The fludarabine-cyclophosphamide-rituximab (FCR) regimen has been shown to be effective in previously untreated patients with CLL, with an overall response rate of 88.37% and a median progression-free survival of 67 months 5.
• Ibrutinib-rituximab has been compared to standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, and has been shown to result in superior progression-free survival and overall survival 6.
• The efficacy of front-line therapy with FCR has also been evaluated in the "real-life" setting, with results showing similar overall and clinical complete response rates to those reported in clinical trials, but with shorter progression-free survival 7.

Novel Agents and Targeted Therapies

• Covalent Bruton tyrosine kinase (BTK) inhibitors, such as acalabrutinib, zanubrutinib, and ibrutinib, have been shown to be effective in the treatment of CLL, with survival rates of approximately 88% at 4 years for acalabrutinib and 78% at 7 years for ibrutinib 8.
• B-cell leukemia/lymphoma 2 (BCL2) inhibitors, such as venetoclax, have also been shown to be effective, with an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax 8.
• Phosphoinositide 3'-kinase (PI3K) inhibitors, such as idelalisib and duvelisib, can be prescribed for disease that progresses with BTK inhibitors and venetoclax, but require close monitoring for adverse events 8.