Imatinib reduces TNF-α levels in CML patients; persistent levels correlate with poor response

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Frontiers in Medicine Published April 1, 2026 Medically reviewed May 1, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider TNF-α as a potential adjunctive prognostic marker in CML, pending prospective validation.

A single-center, prospective observational cohort study at Safdarjung Hospital in New Delhi followed 40 chronic-phase chronic myeloid leukemia (CML) patients receiving first-line imatinib treatment. The study assessed the pharmacodynamic and prognostic role of serum TNF-α levels over a follow-up period of 5–7 months after starting therapy. No comparator group was reported.

The main finding was a significant reduction in serum TNF-α levels, from a baseline of 259.5 pg/mL to 129.8 pg/mL after imatinib treatment (p < 0.0001). The study reported a strong positive correlation (r = 0.87) between the persistence of elevated TNF-α levels and a poor response to imatinib. A weaker positive correlation (r = 0.45) was found between TNF-α clearance and a good clinical outcome.

Safety and tolerability data were not reported. The study has important limitations: it is observational, conducted at a single center, and has a small sample size of 40 patients. The authors explicitly note the findings show association, not causation. The practice relevance is restrained; the authors suggest TNF-α may be useful as an adjunctive prognostic marker, particularly in resource-poor environments, but this requires appropriate prospective confirmation. It is not suggested as a replacement for standard BCR-ABL1 monitoring.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedMar 2026

View Original Abstract ↓

PurposeChronic Myeloid Leukemia (CML) is characterized by the BCR-ABL1 fusion gene and is effectively managed with tyrosine kinase inhibitors (TKIs). However, therapeutic resistance and the persistence of leukemic stem cells pose challenges to achieving long-term remission. Tumor Necrosis Factor-alpha (TNF-α), a pro-inflammatory cytokine, is implicated in leukemogenesis and resistance, yet its clinical relevance in Indian CML cohorts remains underexplored.ObjectiveThis study investigates the pharmacodynamic and prognostic role of serum TNF-α levels in chronic-phase CML patients receiving first-line imatinib, aiming to evaluate its utility as a biomarker for treatment response.MethodsWe conducted a prospective observational study on 40 CML patients treated at Safdarjung Hospital, New Delhi. Blood samples were taken before treatment and 5–7 months after starting imatinib. ELISA was used to quantify TNF-α levels, and qRT-PCR was used to monitor BCR-ABL1 transcripts. We analyzed clinical and hematologic parameters using appropriate statistical methods.ResultsImatinib treatment significantly reduced serum TNF-α (259.5 to 129.8 pg/mL; p < 0.0001), mirroring the observed decrease in BCR-ABL1 transcripts. Basically, if TNF-α stuck around (r = 0.87), patients responded poorly, whereas good outcomes correlated with its quicker clearance (r = 0.45).ConclusionOur data suggest that TNF-α represents a clinically relevant pharmacodynamic and prognostic biomarker for patients with chronic-phase CML receiving imatinib therapy. A decline in TNF-α levels was associated with a favorable therapeutic outcome, whereas failure of TNF-α to decline was indicative of an inferior outcome. TNF-α does not replace qRT-PCR–based monitoring of BCR-ABL1; however, it may be useful as an adjunctive prognostic marker, especially in resource-poor environments, pending appropriate prospective confirmation.