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Ixazomib-based regimens for relapsed/refractory multiple myeloma: are real-world data compatible with clinical trial outcomes? A multi-site Israeli registry study

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Abstract

Ixazomib, the first oral proteasome inhibitor (PI), has been approved for the treatment of relapsed refractory multiple myeloma (RRMM) in combination with lenalidomide and dexamethasone, based on the TOURMALINE-MM1 phase 3 trial, which demonstrated the efficacy and safety of this all-oral triplet, compared with lenalidomide-dexamethasone. However, clinical trial outcomes do not always translate into real-world outcomes. The aim of this study was to assess the outcomes of ixazomib-based combination for treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least one cycle of ixazomib-based treatment combination between June 2013 and June 2018 were identified. Data was extracted from medical charts focusing on demographics, disease characteristics, prior treatment, and responses. Primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), safety, and tolerability. A total of 78 patients across 7 sites were retrospectively included. Median follow-up was 22 months. Median age was 68 (range 38–90). Sixty-four percent received ixazomib in 2nd line, 19% in 3rd line. Overall, 89% of patients had been exposed to PIs (bortezomib 87%) prior to IRd, 41% to IMiDs. Twenty-nine (48%, of 60 available) had high (t(4:14), t(14:16), del17p) or intermediate (+1q21) risk aberrations. Most patients (82%) received ixazomib in combination with lenalidomide and dexamethasone. An exploratory assessment for disease aggressiveness at diagnosis was classified by a treating physician as indolent (rapid control to protect from target organ damage not required) vs aggressive (imminent target organ damage) in 63% vs 37%, respectively. Treatment was well tolerated, with a low discontinuation rate (11%). Median PFS on ixazomib therapy was 24 months (95% CI 17–30). PFS was 77% and 47% at 12 and 24 months, respectively. Median OS was not reached; OS was 91% and 80% at 12 and 24 months, respectively. Higher LDH, older age, and worse clinical aggressiveness were associated with worse PFS, whereas a deeper response to ixazomib (≥ VGPR) and a longer response to first-line bortezomib (≥ 24 m) were associated with an improved PFS on ixazomib. No effect on PFS was found for cytogenetic risk by FISH, ISS/rISS, and prior anti-myeloma treatment. Ixazomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting, regardless to cytogenetic risk, with a PFS of 24 months comparable with clinical trial data. This regimen had most favorable outcomes among patients who remained progression-free more than 24 months after a bortezomib induction and for those who have a more indolent disease phenotype.

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Authors and Affiliations

  1. Department of Hematology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

    Yael C. Cohen, Svetlana Trestman, Roy Vitkon & Irit Avivi

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Yael C. Cohen, Hila Magen & Irit Avivi

  3. Chaim Sheba Medical Center, Ramat Gan, Israel

    Hila Magen

  4. Rambam Medical Center, Haifa, Israel

    Noa Lavi & Nethanel Horowitz

  5. Hematology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    Moshe E. Gatt & Adir Shaulov

  6. Hematology Unit, HaEmek Medical Center, Afula, Israel

    Evgeni Chubar

  7. Hematology Unit, Bnai-Zion Medical center, Haifa, Israel

    Natalia Kreiniz & Tamar Tadmor

  8. The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

    Tamar Tadmor

  9. Department of Hematology, Soroka Medical Center, Be’er Sheva, Israel

    Ory Rouvio

  10. Hematology, Kaplan Medical Center, Affiliated with Hadassah and Hebrew University Medical School, Rehovot, Israel

    Olga Shvetz

  11. Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Tomer Ziv-Baran

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  1. Yael C. Cohen
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  2. Hila Magen
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  9. Svetlana Trestman
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  10. Roy Vitkon
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  13. Adir Shaulov
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  15. Irit Avivi
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Corresponding author

Correspondence to Yael C. Cohen.

Ethics declarations

The study was conducted in accordance with the declaration of Helsinki and was approved by the institutional ethic committees in 8 sites (Chaim Sheba, Rambam, Hadassah, HaEmek, Bnai-Zion, Soroka, Kaplan, and Tel Aviv Sourasky medical centers).

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Cohen, Y.C., Magen, H., Lavi, N. et al. Ixazomib-based regimens for relapsed/refractory multiple myeloma: are real-world data compatible with clinical trial outcomes? A multi-site Israeli registry study. Ann Hematol 99, 1273–1281 (2020). https://doi.org/10.1007/s00277-020-03985-9

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  • DOI: https://doi.org/10.1007/s00277-020-03985-9

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