Data for Elotuzumab Support Further Investigation in JAK Inhibitor–Based Combinations in Myelofibrosis

Final results from a single-institution phase 2 study (NCT04517851) demonstrated that treatment with single-agent elotuzumab (Empliciti) was safe and efficacious in patients with myelofibrosis who were not candidates for JAK inhibitors, supporting further investigation of the agent.

Findings presented at the 2025 EHA Congress showed that in treated patients (n = 15), the vast majority of adverse effects (AEs) possibly related to elotuzumab were grade 1 or 2. Grade 1 AEs possibly related to treatment included acute pain during infusion (n = 1), bone pain (n = 1), diarrhea (n = 4), dizziness (n = 2), flushing (n = 1), headache (n = 2), paresthesia (n = 1), pruritus (n = 1), voice alteration/hoarseness (n = 1), increased alanine aminotransferase (ALT) levels (n = 1), and hyper glycemia (n = 1).

Grade 2 AEs possibly related to treatment included fever (n = 1), chills as an infusion-related reaction (n = 2), fever as an infusion-related reaction (n = 1), pharyngitis (n = 1), and elevated ALT levels (n = 1). Grade 3 AEs possibly related to treatment comprised diarrhea (n = 1) and elevated aspartate aminotransferase levels (n = 1).

Regarding efficacy, patients achieved an overall response rate (ORR) of 33%; responses comprised a clinical improvement in anemia (n = 2), major platelet response (n = 1), clinical improvement in symptoms (n = 1), and both clinical improvement in symptoms and major platelet response (n = 1).

“Elotuzumab is active in myelofibrosis and has an excellent safety profile,” lead study author Prithviraj Bose, MD, and colleagues wrote in a poster presentation of the data. “Combination studies with JAK inhibitors may be warranted.”

Bose is a professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

Phase 2 Trial Overview

Investigators enrolled adult patients with primary myelofibrosis or post–polycythemia vera/ essential thrombocytosis myelofibrosis who were not candidates for treatment with a JAK inhibitor, based on the opinion of the treating physician. Notably, prior treatment with a JAK inhibitor was permitted. Patients were required to have disease harboring JAK2 V617F mutations, and intermediate- or higher-risk disease was needed.² An ECOG performance status of 0 to 2 or a Karnofsky performance status of at least 60% was also required for enrollment.

All enrolled patients received elotuzumab intravenously at 10 mg/kg once per week for 8 weeks, then 20 mg/kg once every 4 weeks.¹ Treatment continued for a maximum of 36 cycles, or until disease progression or unacceptable toxicity.

ORR served as the trial’s primary end point.² Secondary end points included safety, duration of response (DOR), time to next treatment, complete response rate, partial response rate, rate of clinical improvement, platelet response rate, and changes in bone marrow fibrosis grade.

Additional Data

At the time of the final analysis, 1 patient remained on study treatment.¹ Among the 14 patients who discontinued treatment, reasons for discontinuation included no response (n = 8), completing 36 cycles of treatment (n = 4), leukemia transformation (n = 1), and death from gastrointestinal bleeding unrelated to elotuzumab (n = 1). Four patients from the population died, including 1 during the study.

Findings also showed that the median time to response was 2.8 months (range, 0.1-3.7), and the median DOR was 11.1 months (range, 3-32.6). The median overall survival was not reached (range, 5.6-38).

The median treatment duration was 6.6 months (range, 0.9-35.4), and patients received a median of 7 cycles of treatment (range, 1-36). The median follow-up was 26.9 months (range, 10.3-38) in living patients.

Notably, 1 patient experienced a transformation from marrow fibrosis grade 3 to grade 2 after 2.8 months of treatment, and this was sustained through 36 cycles of treatment. Another patient experienced a hemoglobin level increase of more at least 2 g/dL; however, this patient was off the study prior to week 12.

References

1. Bose P, Pemmaraju N, Masarova L, et al. Final results of a pilot study of elotuzumab in patients with myelofibrosis. Presented at: 2025 EHA Congress; June 12-15, 2025; Milan, Italy. Abstract PF833.
2. Elotuzumab for the treatment of JAK2-mutated myelofibrosis. ClinicalTrials.gov. Updated April 4, 2025. Accessed July 15, 2025. https://clinicaltrials.gov/study/NCT04517851