Chronic Lymphocytic Leukemia (CLL) Medication

Updated: Feb 03, 2017
  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Medication Summary

Chlorambucil (an alkylating agent) and fludarabine (a purine nucleoside analogue that acts as an antimetabolite) are commonly used in the treatment of chronic lymphocytic leukemia (chronic lymphoid leukemia, CLL). Purine analogues, fludarabine in particular, are very active against CLL. Ibrutinib is indicated for CLL including patients who are treatment-naïve or have been previously treated. It is also indicated for patients who carry a deletion in chromosome 17 (del 17p CLL), which is associated with poor responses to standard treatment.

Fludarabine produces remissions in a significant proportion of patients. It appears to induce apoptosis in malignant lymphocytes upon exposure.

Biologic agents are increasingly used in the treatment of CLL, typically in combination with chemotherapeutic agents. These biologic agents include several monoclonal antibodies (eg, rituximab) and the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib.


Antineoplastic Agents

Class Summary

Antineoplastic agents act by inhibiting the key factors responsible for neoplastic transformation of cells.

Pentostatin (Nipent)

Pentostatin inhibits adenosine deaminase, resulting in deoxyadenosine and deoxyadenosine 5+-triphosphate accumulation that may inhibit DNA or RNA synthesis, causing cell death.

Chlorambucil (Leukeran)

Chlorambucil is a nitrogen mustard derivative with bifunctional alkylating activity. It forms intrastrand crosslinks, interfering with DNA replication and RNA transcription and translation.

Fludarabine (Fludara)

A nucleotide analogue of vidarabine, fludarabine is converted to 2-fluoro-ara-A, which enters the cell and is phosphorylated to form active metabolite 2-fluoro-ara-ATP, which inhibits DNA synthesis. Inhibits DNA polymerase and ribonucleotide reductase as well as DNA primase and DNA ligase I.


Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on B-cells, T-cells, and almost all CLL cells. It binds to the CD52 receptor of the lymphocytes, which slows the proliferation of leukocytes.

Rituximab (Rituxan)

Rituximab is a humanized murine monoclonal antibody against CD20, an antigen found on B-cells. This agent binds CD20 on lymphocytes and induces apoptosis as well as initiating complement-mediated killing of bound cells. Because CLL B-cells have low levels of CD20 expression, increased doses of rituximab may be necessary.

Ofatumumab (Arzerra)

Ofatumumab is an anti-CD20 human monoclonal antibody that inhibits B-cell activation in early stages. It is indicated for CLL refractory to fludarabine and alemtuzumab, for previously untreated CLL in combination with chlorambucil, as extended treatment (as a single agent) for patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL, and for refractory CLL in combination with fludarabine and cyclophosphamide.

Obinutuzumab (Gazyva)

Obinutuzumab is a CD20-directed cytolytic antibody, which, upon binding to CD20, mediates B-cell lysis. Mediation may be (1) through engagement of immune effector cells, (2) by directly activating intracellular death-signaling pathways, and/or (3) by activation of the complement cascade. The CD20 antigen is expressed on the surface of pre–B cells and mature B lymphocytes. The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. It is indicated for previously untreated CLL in combination with chlorambucil.

Ibrutinib (Imbruvica)

Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor that forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. It is indicated for CLL including patients who are treatment-naïve or have been previously treated. It is also indicated for patients who carry a deletion in chromosome 17 (del 17p CLL), which is associated with poor responses to standard treatment.

Idelalisib (Zydelig)

Idelalisib is a phosphoinositide 3-kinase (PI3K) delta inhibitor. Idelalisib induces apoptosis and inhibits proliferation in cell lines derived from malignant B cells and in primary tumor cells; also inhibits several cell- signaling pathways, including B cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in trafficking and homing of B cells to the lymph nodes and bone marrow. It is indicated relapsed chronic lymphocytic leukemia (CLL).

Venetoclax (Venclexta)

Venetoclax is a selective inhibitor of the B-cell lymphoma 2 (Bcl-2) regulator protein, an antiapoptotic protein. Overexpression of Bcl-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutic agents. It is indicated for patients with CLL with 17p deletion, as detected by an FDA approved test, who have received at least 1 prior therapy.