Rituximab in Lymphoma and Chronic Lymphocytic Leukemia: A Clinical Practice Guideline, Version 3

Recommendation 1

Aggressive Histology B-cell Lymphomas, Including Burkitt Lymphoma: First-line, Second-line and Maintenance Treatment and Patients with Human Immunodeficiency Virus (HIV)-associated Lymphomas

Previously Untreated Patients

1. Previously untreated patients with aggressive histology CD20-positive B-cell lymphomas who are candidates for treatment with curative intent and will receive combination chemotherapy with curative intent (including cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], CHOP-like, or similar dose-intense regimens) should receive this therapy in combination with rituximab

Patients with Relapsed/Refractory Disease

2. For previously treated patients with aggressive histology CD20-positive B-cell lymphomas:
   
   
   
   1. There is insufficient evidence at this time to support treatment with a rituximab-containing chemotherapy regimen in patients who have been previously treated with a rituximab-containing chemotherapy regimen.
   
   
   2. If patients have not previously received rituximab as part of their treatment regimen, the addition of rituximab to chemotherapy is reasonable.
   
   
   
   

Rituximab Maintenance Treatment

3. There is insufficient evidence at this time to support the use of maintenance rituximab in aggressive histology B-cell lymphomas.

Patients with HIV-Associated Lymphomas

4. Previously untreated patients with HIV-related lymphoma with a CD4 count ≥50/mm³ who are candidates for treatment with curative intent and will receive combination chemotherapy with curative intent (including CHOP, CHOP-like, or similar dose-intense regimens), should receive this therapy in combination with rituximab. The addition of rituximab to chemotherapy in patients with CD4 <50/mm³ is not recommended.

Recommendation 2

Indolent Histology B-cell Lymphomas: First-line, Second-line, and Maintenance Treatment and Patients with Asymptomatic CD20-positive B-cell Lymphomas

Previously Untreated Patients

1. Previously untreated patients with indolent histology CD20-positive B-cell lymphomas, excluding small lymphocytic lymphoma (SLL), who are appropriate candidates for chemotherapy, should receive their chemotherapy in combination with rituximab.


2. For patients with indolent histology CD20-positive B-cell–histology lymphomas, excluding SLL, who are candidates for therapy, but not combination chemotherapy, rituximab monotherapy is a reasonable option.

Patients with Relapsed/Refractory Disease

3. For previously treated patients with indolent histology CD20-positive B-cell lymphomas, excluding SLL:
   
   
   
   1. Patients who have not previously received rituximab and who are appropriate candidates for chemotherapy should receive this chemotherapy in combination with rituximab or as rituximab monotherapy.
   
   
   2. Patients who have previously received rituximab (including combination rituximab chemotherapy, rituximab monotherapy, or maintenance rituximab) and who have achieved a response of at least one year's duration from the last rituximab administration and who are appropriate candidates for therapy should receive this therapy in combination with rituximab or as rituximab monotherapy.
   
   
   
   

Rituximab Maintenance Treatment

4. For patients with indolent histology CD20-positive B-cell lymphomas, excluding SLL, who respond to treatment with combination chemotherapy and/or rituximab, this treatment should be followed by the use of maintenance rituximab.

Patients with Asymptomatic CD20-Positive B-Cell Lymphomas

5. There is insufficient evidence at this time to support or refute upfront treatment with rituximab monotherapy for asymptomatic indolent histology CD20-positive B-cell lymphomas.

Recommendation 3

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Previously Untreated Patients

1. Patients with previously untreated chronic lymphocytic leukemia (CLL)/SLL, who are appropriate candidates for fludarabine-based chemotherapy, should receive this treatment in combination with rituximab.


2. In patients with previously untreated CLL/SLL who are appropriate candidates for chlorambucil chemotherapy, the addition of rituximab can be considered.

Patients with Relapsed/Refractory Disease

3. Patients with relapsed or refractory CLL/SLL, who are appropriate candidates for fludarabine-based chemotherapy, should receive this treatment in combination with rituximab.

Recommendation 4

Hepatitis B Virus Reactivation in All Patients Treated with Rituximab

The Hematology Disease Site Group (DSG) recommends that all patients be screened for surface antigen for hepatitis B (HBsAg) and for hepatitis B core antibody (HBcAb) prior to treatment with rituximab. Consultation with an expert in hepatitis B virus (HBV) should be considered for all patients who test positively for HBV. Patients who are HBsAg positive should receive prophylactic antiviral therapy during and after rituximab. Patients who are HBsAg negative/HBcAb positive should be considered for either prophylactic antiviral therapy, close monitoring for viral reactivation, and/or should be followed by an expert in HBV. In the absence of active hepatitis (elevated transaminases), it is not usually necessary to delay rituximab. In most cases, HBV screening and management can occur in parallel with non-Hodgkin lymphoma/CLL treatment.