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2024-05-21T10:42:22.000Z

Auto-HCT in newly diagnosed MM with del(17p): real-world outcomes

May 21, 2024
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Learning objective: After reading this article, learners will be able to cite a new clinical development in MF.

The median survival for patients with multiple myeloma (MM) has surpassed 10 years following the introduction of novel therapies, such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. However, deletion of the short arm of chromosome 17 (17p13.1; del[17p]) remains one of the most powerful predictors of poor outcomes.

During the 50th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Marcoux et al. presented a real-world study investigating outcomes with upfront autologous hematopoietic stem cell transplantation (auto-HCT) in newly diagnosed MM (NDMM) with del(17p).1 Here, we summarize the key findings.

Methods1

  • This was a single-center retrospective study conducted in patients with NDMM and del(17p) receiving upfront auto-HCT between 2008 and 2018.
  • The primary endpoints were progression-free survival (PFS) and overall survival (OS).
  • Secondary endpoints were hematologic response and measurable residual disease (MRD) status posttransplantation.

Key findings1

  • Overall, 115 patients with del(17p) were included.
    • Median age at auto-HCT was 62 years and 55% were male.
  • Post-induction therapy, 29% of patients achieved an MRD negative ≥very good partial response (VGPR) prior to auto-HCT. This improved to 55% at Day 100 post-auto-HCT and at best auto-HCT response (Figure 1.)

Figure 1. Key real-world outcomes with auto-HCT in NDMM with del(17p)* 

Auto-HCT, autologous hematopoietic stem cell transplantation.
*Adapted from Marcoux, et al.1

  • At a median follow-up of 31.4 months, median PFS for the entire cohort was 19.9 and OS was 71.5 months; 5-year PFS and OS were 32% and 53%, respectively.
  • Patients with both t(4;14) and del(17p) had poor outcomes, with a median PFS of 11.5 months and OS of 22.4 months. However, patients achieving MRD negative ≥VGPR prior to auto-HCT had a median PFS of 71.9 months and OS of 92.4 months.
  • In multivariable analysis, female sex was significantly associated with worse PFS, while MRD negativity and maintenance therapy were significantly associated with improved PFS post auto-HCT (Figure 2).
    • Regarding OS, female sex and presence of t(4;14) were significantly associated with worse OS, while Karnofsky performance status of ≥90 was significantly associated with improved OS.

Figure 2.  Multivariate analysis for A progression free survival and B overall survival*

Auto-HCT, autologous hematopoietic stem cell transplantation; CI, confidence interval; CR, complete response; HCT-CI, Hematopoietic Cell Transplantation-specific Comorbidity Index; KPS, Karnofsky performance status; MRD, minimal residual disease.
*Data from Marcoux, et al.1

Key learnings 

  • This study confirms del(17p) as a high-risk cytogenetic abnormality, resulting in unfavorable outcomes in patients with MM despite management with novel therapies, auto-HCT, and posttransplant maintenance.
  • The co-occurrence of del(17p) and t(4;14) markedly reduced survival rates, while MRD-negativity posttransplant and the use of maintenance therapy improved PFS.
  • The persistent suboptimal outcomes in this patient population underscore a need for the development of new treatment modalities.

  1. Marcoux C, Pasvolsky O, Milton DR, et al. Real-world outcomes of upfront autologous hematopoietic stem cell transplantation in newly diagnosed multiple myeloma patients with del (17p). Abstract #A273. 50th Annual Meeting of the EBMT. Apr 14-17, 2023; Glasgow, UK.

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