Chronic lymphocytic leukemia medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is immunochemotherapy. Asymptomatic chronic lymphocytic leukemia patients are managed with observation and follow-up, whereas symptomatic chronic lymphocytic leukemia patients are treated with immunochemotherapy. Immunochemotherapies used for the treatment of chronic lymphocytic leukemia patients include purine analogues, alkylating agents, monoclonal antibodies, corticosteroids, tyrosine kinase inhibitors, and B-cell receptor pathway inhibitors. Radiation therapy is not recommended for the management of chronic lymphocytic leukemia patients.
Immunochemotherapy
- The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is immunochemotherapy.
- Asymptomatic chronic lymphocytic leukemia patients are managed with observation and follow-up, 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 might be observed as:
- An increase of greater than 50% over a 2-month period
- A lymphocyte doubling in a period shorter than six months
- Immunochemotherapeutic agents used for the treatment of chronic lymphocytic leukemia patients include:
- Purine analogues such as:
- Alkylating agents such as:
- Monoclonal antibodies such as:
- Immunomodulatory agents such as:
- Corticosteroids such as:
- Tyrosine kinase and B-Cell receptor pathway inhibitors such as:
- Idelalisib (targets phosphoinositide 3-kinase delta)
- Ibrutinib (targets bruton tyrosine kinase)
- The optimal immunochemotherapeutic regimen used for the management of chronic lymphocytic leukemia patients 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 0-2 Binet stage A | Rai stage 3-4 Binet stage B-C | ||||||||||||||||||||||||||
Patients managed by observation and close follow-up | Evaluate patients by Cumulative Index Illness Rating Scale | ||||||||||||||||||||||||||
Fit patients (CIRS <6) | Frail patients (CIRS ≥6) | ||||||||||||||||||||||||||
FISH chromosomal analysis | |||||||||||||||||||||||||||
Immunochemotherapeutic regimens for the management of patients without chromosome 17p deletion or chromosome 11q deletion can be found here | Immunochemotherapeutic regimens for the management of patients with chromosome 17p deletion can be found here | Immunochemotherapeutic regimens for the management of patients with chromosome 11q 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 (or younger than 70 years of age with a poor performance status) include (in order of preference):[1]
- 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 with a good performance status 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 (or younger than 70 years of age with a poor performance status) 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 with a good performance status 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
- Venetoclax AND rituximab
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 the Management of Patients with Chromosome 11q Deletion
First Line Therapy
- Preferred immunochemotheraptic regimens for the treatment of such patients who are older than 70 years of age (or younger than 70 years of age with a poor performance status) 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 of such patients who are younger than 70 years of age with a good performance status include (in order of preference):
- Fludarabine AND cyclophosphamide AND rituximab
- Bendamustine ± rituximab
- Pentostatin AND cyclophosphamide AND rituximab
- Obinutuzumab AND chlorambucil
Supportive Therapy
Opportunistic Infections Prophylaxis
- Vaccines recommended for chronic lymphocytic leukemia patients include:
- Pneumococcal vaccine administered every five years
- Influenza vaccine administered annually
- Live attenuated vaccines should be avoided among chronic lymphocytic leukemia patients.
- Other strategies for the prevention of opportunistic infections include:
- Sulfamethoxazole/trimethoprim can be administered to patients receiving purine analogues as a prophylaxis for pneumocystis pneumonia infection.
- Acyclovir can be administered to patients receiving purine analogues as a prophylaxis for herpes simplex virus infection.
Autoimmune Cytopenia Prophylaxis
- Corticosteroids is recommended for the management of autoimmune cytopenia among chronic lymphocytic leukemia patients. Other therapeutic measures may include:
- Romiplostim is recommended for the management of autoimmune thrombocytopenia among chronic lymphocytic leukemia patients.
Thromboprophylaxis
- A daily aspirin dose is recommended among chronic lymphocytic leukemia patients who receive lenalidomide while their platelet count is greater than 50000 per microliter.
- However, aspirin administration is not needed for such chronic lymphocytic leukemia patients who are already on warfarin.
Radiation Therapy
- Radiation therapy is not recommended for the management of chronic lymphocytic leukemia patients.
References
- ↑ Thompson PA, Tam CS, O'Brien SM, Wierda WG, Stingo F, Plunkett W, Smith SC, Kantarjian HM, Freireich EJ, Keating MJ (January 2016). "Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia". Blood. 127 (3): 303–9. doi:10.1182/blood-2015-09-667675. PMC 4760129. PMID 26492934.