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

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.)

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.

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.