Progression-Free Survival in Relapsed Multiple Myeloma Extended With Ixazomib, Data Show

Despite challenges such as high attrition rates and adverse events, the trial highlights the value of established therapies in improving outcomes, particularly in regions with limited access to CAR T cells and bispecific antibodies.

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A new analysis from the phase 3 ACCoRD trial (NCT01564537) offers compelling evidence that consolidation and maintenance therapy using ixazomib (Ninlaro; Takeda) after salvage autologous hematopoietic stem cell transplantation (HSCT) significantly improves progression-free survival (PFS) in patients with relapsed multiple myeloma compared with observation alone.¹

These findings were published recently in The Lancet Haematology.

The ACCoRD trial, conducted across 79 UK hospitals, enrolled patients 18 years or older with relapsed multiple myeloma requiring treatment for first progressive disease at least 12 months after an initial autologous HSCT. Following salvage HSCT, 206 patients were randomly assigned to either consolidation with ixazomib, thalidomide, and dexamethasone (ITD), followed by maintenance with single-agent ixazomib, or observation. The study’s primary end point was PFS, with safety analyzed per protocol.

Participants had a median age of 62.5 years, and 69% were men. Most (61%) had received a proteasome inhibitor as part of their initial treatment, and 8% had previously received lenalidomide maintenance. Cytogenetic results revealed that 64% of participants were standard risk; 27%, high risk; and 9%, ultra–high risk.

ACCoRD Key Findings

At a median follow-up of 27 months, the results demonstrated a clear benefit for consolidation and maintenance therapy:

• PFS: The median PFS was 20 months in the consolidation and maintenance group vs 13 months in the observation group (HR, 0.55; 95% CI, 0.39-0.78; P = .0006).
• Safety profile: Serious adverse events were more frequent in the consolidation and maintenance groups (32%) than in the observation group (7%), with infections and upper respiratory tract infections being the most common events; no treatment-related deaths were reported

The results underscore the efficacy of ixazomib-based therapy in prolonging disease control without compromising subsequent treatment options or overall survival, pending longer-term follow-up.

The trial’s results align with prior studies in the frontline setting, which have shown the benefits of maintenance therapy. Notably, the ACCoRD trial provides the first robust evidence for this strategy after salvage HSCT in relapsed multiple myeloma. Unlike the GMMG ReLApsE study, which found no PFS benefit for lenalidomide-based maintenance after salvage HSCT, ACCoRD participants experienced superior PFS with ixazomib, potentially due to differences in patient populations and study design.

Clinical Implications

The findings support the role of salvage HSCT followed by consolidation and maintenance therapy as a viable approach in the modern treatment landscape for relapsed multiple myeloma. Ixazomib’s oral administration offers a practical and tolerable option for long-term management, avoiding the challenges associated with multiagent regimens and corticosteroid-related toxicity.

However, the rapidly evolving therapeutic landscape, including the introduction of novel immunotherapies, may influence the selection of agents for posttransplant maintenance in the future. Additionally, the study raises critical questions about identifying patients who are most likely to benefit based on factors such as cytogenetic risk and response to prior treatments.

According to previous research published in The Lancet Haemotology, despite challenges such as high attrition rates and adverse events like peripheral neuropathy and infections, the trial findings highlight the value of established therapies in improving outcomes, particularly in regions with limited access to modern immunotherapies like CAR T cells and bispecific antibodies.² The author noted that these findings reinforce the importance of continued therapy with widely available agents after HSCT, underscoring their role in prolonging disease control in relapsed multiple myeloma.

Future Directions

Long-term follow-up of the ACCoRD trial will be essential to evaluate overall survival, second PFS, and the impact of consolidation and maintenance therapy on health-related quality of life.¹ These data will help refine maintenance strategies and ensure that treatment is tailored to individual patient profiles.

The ACCoRD trial established consolidation and maintenance with ixazomib as a superior strategy to observation after salvage HSCT for relapsed multiple myeloma, the study stated. As the therapeutic landscape continues to evolve, these findings provide a crucial benchmark for integrating maintenance therapy into routine clinical practice.

References

1. Cook G, Ashcroft AJ, Senior E, et al. Ixazomib as consolidation and maintenance versus observation in patients with relapsed multiple myeloma eligible for salvage autologous stem-cell transplantation (Myeloma XII [ACCoRD]): interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol. 2024;11(11):e816-e829. doi:10.1016/S2352-3026(24)00249-7

2. Mai EK. Continued need for autologous transplantation in relapsed myeloma. Lancet Haematol. 2024;11(11):e804-e805. doi:10.1016/S2352-3026(24)00277-1