How to manage recurrent fever in a myelodysplastic syndrome (MDS) patient on momelotinib (telatuberdinib)?

Management of Recurrent Fever in MDS Patients on Momelotinib

Immediately initiate broad-spectrum antibiotics at the first sign of fever without waiting for culture results, as this is mandatory in MDS patients and represents a significant cause of morbidity and mortality. 1, 2

Immediate Fever Management Algorithm

First-Line Response to Fever

• Start empiric broad-spectrum antibiotics promptly upon fever detection or any symptoms suggesting infection, as rapid antibiotic initiation is mandatory and directly impacts survival in neutropenic MDS patients 1, 2, 3

• Obtain blood cultures, urinalysis with culture, and chest imaging before antibiotics if feasible, but do not delay antibiotic administration to wait for these results 2

• Check complete blood count with differential to assess absolute neutrophil count, as neutropenia (<1,000 neutrophils/μL) significantly increases infection risk independent of MDS subtype 4

Adjunctive G-CSF Consideration

• Consider short-term G-CSF during severe infections in neutropenic patients, though this indication lacks formal validation 1, 2, 3

• G-CSF can improve neutropenia in 60-75% of cases during active infection, but prolonged prophylactic use has not demonstrated survival benefit and is not recommended 1, 3

• Do not withhold G-CSF during active severe infection with neutropenia, even though routine prophylactic use is discouraged 3

Infection Source Investigation

Common Infection Sites in MDS

• Bacterial pneumonia and skin abscesses are the most common infections in MDS patients and should be the primary focus of clinical examination 4

• Infection accounts for 64% of deaths in MDS patients, making it more common than acute leukemia transformation as a cause of mortality 4

Atypical Pathogens in Recurrent Fever

For patients with recurrent or refractory fever despite appropriate antibiotics:

• Consider nontuberculous mycobacterial (NTM) infection, particularly in patients with progressive pancytopenia, as NTM can cause disseminated infection in MDS patients similar to AIDS patients 5, 6

• Obtain sputum cultures, broncho-alveolar lavage fluid, and bone marrow cultures for mycobacterial testing if fever persists beyond 72 hours of broad-spectrum antibiotics 5, 6

• For MDS patients with recurrent mixed infections and monocyte absence, consider MonoMAC syndrome with GATA2 germline mutation and perform metagenomic next-generation sequencing 6

Momelotinib-Specific Considerations

Drug Continuation Decision

While the provided evidence does not specifically address momelotinib management during infection, the general principle for MDS patients is:

• Temporarily hold myelosuppressive drugs during active severe infection to allow neutrophil recovery, though this must be balanced against disease control needs 1

• Reassess bone marrow function and consider whether fever represents disease progression versus infection, as this determines whether treatment escalation is needed 3

Supportive Care During Fever Episodes

Transfusion Support

• Maintain hemoglobin ≥8 g/dL (or 9-10 g/dL with cardiovascular comorbidities) during infection to optimize oxygen delivery and immune function 1, 3

• Provide platelet transfusions if platelets <50,000/mm³ with active bleeding or if invasive procedures are needed 1

Monitoring Parameters

• Monitor for hemophagocytosis on bone marrow examination if pancytopenia worsens during infection, as this can occur with disseminated infections in MDS 5

• Reassess complete blood count every 48-72 hours during active infection to track response to therapy 3

Critical Pitfalls to Avoid

• Never delay broad-spectrum antibiotics in febrile MDS patients to obtain cultures or await specialist consultation, as this directly increases mortality 1, 2, 3

• Do not use prophylactic antibiotics or G-CSF routinely in neutropenic MDS patients outside of active infection, as this has not shown survival benefit 1, 2

• Do not assume fever is always bacterial—if fever persists beyond 72 hours of appropriate antibiotics, aggressively pursue atypical pathogens including mycobacteria and fungi 5, 6

• For recurrent fever patterns, consider non-infectious causes including disease progression to higher-risk MDS or transformation to AML, requiring bone marrow reassessment 3