Sandbox:therapy

Immunochemotherapy

• The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is combination immunochemotherapy.
• Asymptomatic chronic lymphocytic leukemia patients are managed with observation, whereas symptomatic chronic lymphocytic leukemia patients are treated with immunochemotherapy.
• Indications to initiate immunochemotherapy among patients with chronic lymphocytic leukemia include:

• Symptomatic chronic lymphocytic leukemia patients presenting with:

• Fever of unknown origin (>38.1°C for a period greater than two weeks)
• Night sweats for more than one month
• Unintentional significant weight loss over a period of six months

• Patients presenting with thrombocytopenia or anemia due to bone marrow failure
• Patients presenting with refractory autoimmune hemolytic anemia or refractory autoimmune thrombocytopenia
• Evidence of symptomatic splenomegaly, with the spleen being palpated more than 6cm below the costal margin
• Evidence of symptomatic progressive lymph nodes swelling, with a size greater than 10 cm in diameter
• Evidence of a rapidly progressive lymphocytosis, which may be indicated by:

• An increase of greater than 50% over a 2-month period
• A lymphocyte doubling period shorter than six months

• Immunochemotherapies for chronic lymphocytic leukemia include purine analogues, alkylating agents, monoclonal antibodies, steroids, corticosteroids, Tyrosine kinase inhibitors, and B-cell receptor pathway inhibitors.

• Purine analogues used for the management of chronic lymphocytic leukemia patines may include:

• Cladribine
• Fludarabine
• Pentostatin

• Alkylating agents used for the management of chronic lymphocytic leukemia patients may include:

• Bendamustine
• Chlorambucil
• Cyclophosphamide

• Monoclonal antibodies used for the management of chronic lymphocytic leukemia patients may include:

• Rituximab
• Ofatumumab
• Obinutuzumab
• Alemtuzumab

• Immunomodulatory agents used for the management of chronic lymphocytic leukemia patients may include:

• Lenalidomide

• Corticosteroids used for the management of chronic lymphocytic leukemia patients may include:

• Methylprednisolone
• Prednisone

• Tyrosine kinase and B-Cell receptor pathway inhibitors used for the management of chronic lymphocytic leukemia patients may include:

• Idelalisib (targets phosphoinositide 3-kinase delta)
• Ibrutinib (targets bruton tyrosine kinase)

• The optimal immunochemotherapeutic regimens used for the management of chronic lymphocytic leukemia depends on a number of factors which include:

• The clinical presentation of the patients
• The performance status of the patients
• The stage of the tumor
• The presence of specific genetic mutations
• First line therapy vs. refractory/relapsed therapy

• The algorithm below summarizes the management approach for chronic lymphocytic leukemia patients:

Initial patients evaluation

History Physical examination Complete blood count

Staging

Rai Staging System Binet Staging System

Rai stage 3-4 Binet stage B-C

Rai stage 0-2 Binet stage A

Evaluate patients by cumulative index illness rating scale

Patients managed by observation and close follow-up

Frail patients (CIRS ≥6)

Fit patients (CIRS <6)

Retixumab/obinutuzumab AND chlorambucil

FISH chromosomal analysis

Immunochemotherapeutic regimens for management of patients without chromosome 17p deletion or chromosome 11q deletion can be found here

Immunochemotherapeutic regimens for management of patients with chromosome 17p deletion can be found here

Immunochemotherapeutic regimens for management of patients with chromosome 17p deletion can be found here

Immunochemotherapeutic regimens for the management of patients without chromosome 17p deletion or chromosome 11q deletion

First line therapy

• Preferred immunochemotheraptic regimens for the treatment of such patients who are older than 70 years of age include (in order of preference):

• Obinutuzumab AND chlorambucil
• Ofatumumab AND chlorambucil
• Rituximab AND chlorambucil
• Bendamustine ± rituximab
• Obinutuzumab
• Fludarabine ± rituximab
• Chlorambucil
• Rituximab
• Cladribine

• Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age include (in order of preference):

• Fludarabine AND cyclophosphamide AND rituximab
• Fludarabine AND rituximab
• Pentostatin AND cyclophosphamide AND rituximab
• Bendamustine AND rituximab

Refractory/relapsed therapy

• Preferred immunochemotheraptic regimens for the treatment of such patients who are older than 70 years of age include (in order of preference):

• Ibrutinib
• Idelalisib ± rituximab
• Fludarabine AND cyclophosphamide AND rituximab (reduced dose)
• Pentostatin AND cyclophosphamide AND rituximab (reduced dose)
• Bendamustine ± rituximab
• High-dose methylprednisolone AND rituximab
• Ofatumumab
• Obinutuzumab
• Lenalidomide ± rituximab
• Alemtuzumab ± rituximab
• Dose-dense rituximab

• Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age include (in order of preference):

• Ibrutinib
• Idelalisib ± rituximab
• Fludarabine AND cyclophosphamide AND rituximab
• Pentostatin AND cyclophosphamide AND rituximab
• Bendamustine ± rituximab
• Fludarabine AND alemtuzumab
• Rituximab AND cyclophosphamide AND doxorubicin AND vincristine AND cytarabine
• Oxaliplatin AND fludarabine AND cytarabine AND rituximab
• Ofatumumab
• Obinutuzumab
• Lenalidomide ± rituximab
• Alemtuzumab ± rituximab
• High-dose methylprednisolone AND rituximab

Immunochemotherapeutic regimens for the management of patients with chromosome 17p deletion

First line therapy

• Preferred immunochemotheraptic regimens for the treatment of such patients regardless the age group include (in order of preference):

• Ibrutinib
• High-dose methylprednisolone AND rituximab
• Fludarabine AND rituximab
• Fludarabine AND cyclophosphamide AND rituximab
• Obinutuzumab AND chlorambucil
• Alemtuzumab ± rituximab
• Rituximab AND chlorambucil

Refractory/relapsed therapy

• Preferred immunochemotheraptic regimens for the treatment of such patients regardless the age group include (in order of preference):

• Ibrutinib
• Idelalisib ± rituximab
• High-dose methylprednisolone AND rituximab
• Lenalidomide ± rituximab
• Ofatumumab
• Oxaliplatin AND fludarabine AND cytarabine AND rituximab

Immunochemotherapeutic regimens for management of patients with chromosome 11q deletion

First line therapy

• Preferred immunochemotheraptic regimens for the treatment such patients who are older than 70 years of age include (in order of preference):

• Obinutuzumab AND chlorambucil
• Ofatumumab AND chlorambucil
• Rituximab AND chlorambucil
• Bendamustine ± rituximab
• Cyclophosphamide AND prednisone ± rituximab
• Fludarabine AND cyclophosphamide AND rituximab (reduced dose)
• Rituximab

• Preferred immunochemotheraptic regimens for the treatment such patients who are younger than 70 years of age include (in order of preference):

• Fludarabine AND cyclophosphamide AND rituximab
• Bendamustine ± rituximab
• Pentostatin AND cyclophosphamide AND rituximab
• Obinutuzumab AND chlorambucil