What are the concerns for a patient with diffuse large B cell lymphoma who received R-CHOP (Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, and Prednisone) therapy 1 week ago, now presenting with neutropenia and low-grade fever?

From the Guidelines

For a patient who received R-CHOP for diffuse large B-cell lymphoma 1 week ago and now presents with an absolute neutrophil count (ANC) of 1000 and low-grade fever, immediate evaluation and management are necessary, and I recommend immediate medical assessment, blood cultures, and empiric broad-spectrum antibiotics such as cefepime 2g IV every 8 hours or piperacillin-tazobactam 4.5g IV every 6 hours. This patient likely has chemotherapy-induced neutropenia with possible neutropenic fever, which requires prompt intervention. The risk of infection increases with the depth and duration of neutropenia, and fever can be an important indicator of infection, as noted in the 2018 guideline update by the American Society of Clinical Oncology (ASCO) and the Infectious Diseases Society of America (IDSA) 1.

Key Considerations

• The patient's low-grade fever in the setting of neutropenia is concerning because even minor infections can rapidly progress to life-threatening sepsis in neutropenic patients.
• The timing of neutropenia (7 days post-chemotherapy) is consistent with the expected nadir period for R-CHOP.
• Hospitalization is typically warranted for close monitoring, especially if the patient appears ill or has comorbidities.
• Granulocyte colony-stimulating factor (G-CSF) such as filgrastim (Neupogen) at 5 mcg/kg subcutaneously daily should be considered to boost neutrophil recovery, particularly in high-risk patients or those with expected prolonged and profound neutropenia, as suggested by the 2006 update of recommendations for the use of white blood cell growth factors 1.

Management Approach

• Immediate medical assessment and blood cultures are crucial.
• Empiric broad-spectrum antibiotics should be initiated promptly, ideally within 2 hours of presentation, as recommended by the 2011 clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer 1.
• The use of CSFs together with antibiotics may be reasonable in high-risk patients, even though the benefits of administration under these circumstances have not been definitively proven, as discussed in the 2000 update of recommendations for the use of hematopoietic colony-stimulating factors 1.
• For future cycles, prophylactic G-CSF starting 24-72 hours after chemotherapy should be considered to prevent recurrent neutropenic episodes, and dose modifications of the chemotherapy regimen may be necessary based on the severity of this episode.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy ZARXIO is indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever [see Clinical Studies (14.1)].

Given the patient has diffuse large B cell lymph lymphoma, is receiving myelosuppressive chemotherapy (R-CHOP), has an absolute neutrophil count of 1000, and a low-grade fever, the use of filgrastim (ZARXIO) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in this patient 2.

• The patient's condition matches the indication for ZARXIO use in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs.
• ZARXIO can help reduce the incidence of febrile neutropenia and its associated complications in this patient.

From the Research

Management of Febrile Neutropenia

• The patient has undergone R-CHOP for diffuse large B cell lymphoma and presents with an absolute neutrophil count of 1000 and a low-grade fever, indicating febrile neutropenia 3.
• Febrile neutropenia is a common complication in cancer patients, particularly those undergoing chemotherapy, and requires prompt empiric antibiotic therapy to prevent severe infection or sepsis 3, 4.

Empiric Antibiotic Therapy

• The selection of empiric antibiotic therapy should be based on patient factors, predicted infecting organism(s), and local microbial resistance patterns 5, 6.
• Broad-spectrum antibiotics with activity against typical gram-positive and gram-negative causative micro-organisms should be initiated as soon as possible, ideally within one hour of recognition of sepsis or septic shock 5, 6.
• Combination therapy with a beta-lactam antibiotic plus an aminoglycoside, such as cefepime plus amikacin or piperacillin-tazobactam plus amikacin, is a common approach for empiric antibiotic therapy in febrile neutropenia 4, 7.

De-escalation of Antibiotic Therapy

• De-escalation of antibiotic therapy should be considered as soon as possible to minimize the risk of antimicrobial resistance and reduce the risk of adverse events 5, 6.
• Biomarkers such as procalcitonin may provide decision support for antibiotic use and guide duration of antibiotic therapy 6.

Specific Considerations

• The patient's low absolute neutrophil count and low-grade fever suggest a high risk of infection, and empiric antibiotic therapy should be initiated promptly 3.
• The choice of empiric antibiotic therapy should take into account the patient's underlying condition, recent antibiotic use, and local resistance patterns 5, 6.