LEN-EOS study: Lenalidomide-associated eosinophilia as a marker of response to induction therapy in multiple myeloma.

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Background: Lenalidomide is an immunomodulatory drug which play an integral role in induction therapy in multiple myeloma. Treatment-emergent eosinophilia has been observed with immunomodulatory drugs, but its clinical significance in multiple myeloma (MM) remains uncertain. This study primarily evaluated the association between lenalidomide-induced eosinophilia and achievement of complete response, very good partial response or better (≥VGPR), over all response (≥PR), following bortezomib–lenalidomide–dexamethasone (VRd) induction in newly diagnosed multiple myeloma (NDMM). Methods: This prospective observational study was conducted between January 2022 and January 2025 at a tertiary cancer institute in India. NDMM patients treated with standard weekly VRd were included. Patients with baseline eosinophilia, active infection or allergy, renal and liver dysfunction were excluded. Absolute eosinophil count (AEC) was assessed at baseline and on Day 29 of cycle 1. Lenalidomide-induced eosinophilia was defined as an increase in AEC ≥250/µL from baseline. Responses were assessed according to International Myeloma Working Group criteria. Associations between eosinophilia and treatment response were evaluated using Fisher’s exact test and logistic regression. Results: Of 213 patients screened, 127 were included for analysis. Median age was 67 years; 84 patients (66.1%) were male and 43 (33.9%) were female. At diagnosis, 32.3% of patients had ISS stage I disease, 29.1% had stage II disease, and 38.6% had stage III disease. All patients received ≥4 cycles of VRd with full-dose lenalidomide. Lenalidomide-induced eosinophilia occurred in 20 patients (15.7%). Patients who developed eosinophilia demonstrated significantly higher response rates: CR was observed in 10 of 20 (50.0%) versus 29 of 107 (27.1%) (OR ~2.7; p = 0.04), ≥VGPR was achieved in 16 of 20 (80.0%) compared with 57 of 107 (53.3%) without eosinophilia (OR ~3.5; p = 0.01). Similarly, ≥PR was achieved in 19 of 20 (95.0%) compared with 78 of 107 (72.9%) (OR ~7.1; p = 0.03). Conclusions: Lenalidomide-induced eosinophilia is significantly associated with higher rates of complete response, deep response (≥VGPR), and overall response following VRd induction in NDMM. Early treatment-emergent eosinophilia may represent a simple, cost-effective biomarker of immune-mediated treatment efficacy and warrants further prospective validation.