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2024-01-31T11:08:19.000Z

TAMARIN trial: Tamoxifen for the treatment of MPN

Jan 31, 2024
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Learning objective: After reading this article, learners will be able to recall key findings from the TAMARIN trial.

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Many therapies for myeloproliferative neoplasms (MPN) address symptom improvement without a focus on reduction in tumor size.1 Tamoxifen, a selective estrogen receptor modulator, has been shown to induce apoptosis in multipotent hematopoietic progenitors whilst sparing normal hematopoietic stem cells; therefore, it is under investigation to target tumor size in patients with stable MPN and without previous thrombotic events.1

Below, we summarize the phase II TAMARIN study (EudraCT 2015-005497-38) investigating tamoxifen in patients with stable MPN; no prior thrombotic events; and mutated JAK2V617F, CALRins5, or CALRdel52 peripheral blood allele burden ≥20%.

TAMARIN study design1

  • In total, 38 patients were enrolled
  • The primary outcome was a ≥50% decrease in mutant allele burden in peripheral blood at 24 weeks
  • Secondary outcomes included a ≥25% decrease in mutant allele burden at 24 weeks and toxicities

Results1

The baseline characteristics are shown in Table 1.

Table 1. Baseline patient characteristics*

Characteristics, % (unless otherwise specified)

Patients
(N = 38)

Mean age, years

66.3

Sex

              Male

71.1

              Female

28.9

Disease subtype

              Essential thrombocythemia

36.8

              Primary myelofibrosis

15.8

              Post-essential thrombocythemia           myelofibrosis

5.3

              Polycythemia vera

28.9

              Post-polycythemia vera myelofibrosis

13.2

*Adapted from Fang, et al.1

Efficacy1

  • Most patients (84%) completed the 24-week treatment plan
  • Overall, three patients met the primary outcome
    • Three patients achieved ≥50% reduction in mutant allele burden
  • Five patients showed a 25% decrease in mutant allele burden at 24 weeks
    • Three of these patients carried the JAK2V617F mutation
    • The two remaining patients carried CALRdel52 and CALRins5 mutations, but these mutations also require increased MPL-JAK-STAT activation to be pathogenic.
  • Six patients remained on treatment beyond 48 weeks

Safety1

The safety profile was manageable and four serious adverse events (SAE) were reported:

  • urinary infection (n = 2) and intracranial hemorrhage (n = 1) not considered related to treatment;
  • vascular disorders (n = 1) considered possibly related to treatment; and
  • no deaths reported.

Conclusion

Tamoxifen was shown to reduce mutant allele burden in a subset of MPN patients who could be identified by hematopoietic stem cell transcriptomic signature before treatment. The primary endpoint (≥50% decrease in mutant allele burden in peripheral blood at 24 weeks) of this phase II study was met and observed in 3 patients. These findings advocate for future clinical studies to test the effectiveness of other selective estrogen receptor modulators in MPN, specifically the Janus kinase 2-signaling pathway.

  1. Fang Z, Fattori GC, McKerrell T, et al. Tamoxifen for the treatment of myeloproliferative neoplasms: A phase II clinical trial and exploratory analysis. Nat Commun. 2023;14(1):7725. DOI: 1038/s41467-023-43175-5

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