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How to sequence BCMA-directed therapies in early relapsed/ refractory multiple myeloma
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Ixazomib in combination with daratumumab and dexamethasone for the treatment of RRMM
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Ixazomib, an oral proteasome inhibitor, is approved in combination with lenalidomide and dexamethasone for the treatment of MM after ≥1 prior therapy. However, lenalidomide is also commonly used in the first-line and lenalidomide-refractory disease is frequent, highlighting the need for lenalidomide-free alternatives in the relapsed/refractory setting. Data from a phase II study (NCT03439293) evaluating ixazomib in combination with daratumumab and dexamethasone (IDd) in RRMM, including those with hard-to-treat and lenalidomide-refractory disease, were presented in the American Journal of Hematology by Delimpasi et al.1
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| Key learnings: |
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At the final analysis of this phase II trial, ORR was 64.4%, with a ≥VGPR of 30.5% in response-evaluable patients treated with IDd (n = 59). |
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Response rates among the subgroups analyzed were 53.3% in patients with high-risk cytogenetics, 58.3% in patients with expanded high-risk cytogenetics, 50.0% in patients aged ≥75 years, and 61.9% in lenalidomide-refractory patients. |
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The median PFS for patients treated with IDd was 16.8 months. Median PFS was comparable in those with high-risk cytogenetics (8.7 months) and in those refractory to lenalidomide (12.6 months). |
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54.1% of patients experienced Grade ≥3 TEAEs, with 1.6% of patients having Grade ≥3 peripheral neuropathy. |
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TEAEs led to dose modifications, reductions, and discontinuations in 62.3%, 36.1%, and 16.4% of patients, respectively. |
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Data presented highlight the IDd regimen as a tolerable treatment option for patients with RRMM, including for those with high-risk features. As an all-oral, lenalidomide-free option, it provides an alternative for potentially difficult to treat patients. |
Abbreviations: IDd, ixazomib-daratumumab-dexamethasone; MM, multiple myeloma; ORR, overall response rate; PFS, progression-free survival; RRMM, relapsed/refractory multiple myeloma; TEAE, treatment-emergent adverse events; VGPR, very good partial response.
- Delimpasi S, Dimopoulos M, Straub J, et al. Ixazomib plus daratumumab and dexamethasone: Final analysis of a phase 2 study among patients with relapsed/refractory multiple myeloma. Am J Hematol. 2024;99(9):1746-1756. DOI: 10.1002/ajh.27382
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