Is Daratumumab (daratumumab) effective in treating chronic fatigue syndrome?

Daratumumab is NOT indicated for chronic fatigue syndrome and should NOT be used for this condition

Daratumumab is a CD38-targeting monoclonal antibody approved exclusively for multiple myeloma treatment, with no evidence, rationale, or safety data supporting its use in chronic fatigue syndrome (CFS). 1

Why Daratumumab is Inappropriate for CFS

Mechanism and Approved Indications

• Daratumumab kills plasma cells through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and direct apoptosis—mechanisms relevant only to malignant plasma cell disorders 1
• The drug is FDA-approved solely for multiple myeloma in combination regimens (daratumumab/lenalidomide/dexamethasone, daratumumab/bortezomib/dexamethasone, or daratumumab/pomalidomide/dexamethasone) 2, 1
• No published trials, case reports, or even theoretical frameworks exist for daratumumab in CFS 3, 4, 5

Significant Safety Concerns

• Infusion-related reactions occur in 42-45% of patients, predominantly during the first infusion 1
• Increased risk of upper respiratory tract infections requiring herpes zoster prophylaxis 1
• Neutropenia and thrombocytopenia are common hematologic toxicities 2
• The drug interferes with blood bank testing by causing positive indirect Coombs tests that persist for 6 months 1
• These risks are only justifiable in life-threatening malignancies, not in CFS 2

Evidence-Based Treatment for Chronic Fatigue Syndrome

First-Line Interventions

• Pulmonary rehabilitation programs and/or inspiratory muscle strength training for 6-12 weeks are recommended as the primary intervention for troublesome fatigue, showing significant improvements in fatigue severity scales, 6-minute walk test, and dyspnea scores 2
• Graded exercise therapy has demonstrated positive effects on physical fatigue in longitudinal studies 2, 3
• Cognitive behavioral therapy has shown the most promising results in systematic reviews of CFS treatments 3

Pharmacological Options (When Non-Pharmacological Approaches Insufficient)

• D-methylphenidate or armodafinil for 8 weeks can be considered for fatigue not related to disease activity, after trying exercise/rehabilitation programs 2
• These neurostimulants have been evaluated in randomized controlled trials specifically for sarcoidosis-associated fatigue, which shares clinical features with CFS 2

Essential Diagnostic Workup Before Treatment

• Rule out diabetes mellitus, thyroid dysfunction, neuroendocrine disorders, depression, obstructive sleep apnoea, vitamin D deficiency (especially 1,25-dihydroxy-cholecalciferol), heart failure, and neurologic disease 2
• Check vitamin B6, B12, folate, ferritin, zinc, magnesium, calcium, and vitamin D levels 6
• Assess for anemia, iron deficiency, electrolyte disturbances, and medication side effects 2, 6

Psychological Interventions

• Solution-focused therapy showed reduction in fatigue for up to 3 months in randomized controlled trials of patients with quiescent inflammatory conditions 2, 6
• Stress management programs demonstrated non-significant trends toward reduced tiredness 2

Critical Pitfall to Avoid

The most dangerous error would be prescribing daratumumab off-label for CFS. This would expose patients to serious immunosuppressive toxicities without any scientific rationale, violate standard-of-care principles, likely be denied by insurance, and potentially cause harm through infections, cytopenias, and infusion reactions in patients who do not have a life-threatening malignancy justifying such risks 2, 1. The experimental cytokine inhibition studies in CFS have focused on IL-1 antagonists (anakinra), not CD38-targeting antibodies 7.