Iberdomide maintenance after ASCT in NDMM: results from the phase II EMN26 trial

Lenalidomide maintenance is currently the standard-of-care treatment for patients with newly diagnosed multiple myeloma (NDMM) following high-dose chemotherapy and autologous stem cell transplantation; however, 24–29% of patients discontinue treatment with lenalidomide due to adverse events (AEs) and poor tolerability.¹

During the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, Van de Donk presented first results from the EMN26 phase II trial (NCT04564703), in which iberdomide, a novel oral cereblon E3 ligase modulator, was investigated as an alternative treatment to address this unmet need. Here, we summarize the key points.

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Study design

EMN26 is an ongoing phase II trial, including 120 patients assigned to three cohorts.

• The primary endpoint was to determine the efficacy of iberdomide through response improvement within six and 12 cycles.
• Secondary endpoints included safety and progression-free survival (PFS).

An outline of the trial design and key eligibility criteria is shown in Figure 1.

Figure 1. EMN26 trial design* 

ASCT, autologous stem cell transplantation; IMiD, immunomodulatory agents; MRD, measurable residual disease; NDMM, newly diagnosed multiple myeloma; NGF, next-generation flow; PD, progressive disease; PI, proteasome inhibitor; PR, partial response.
*Adapted from Van de Donk.^1
†Cohort 3 was added at a later stage.

 Results¹

Both Cohorts 1 and 2 experienced significant improvements in response after six and 12 cycles. After six treatment cycles, patients treated with 1.3 mg iberdomide experienced a larger response improvement. However, after 12 cycles, the 1.0 mg cohort had the largest overall improvement from baseline (Figure 2).

Figure 2. Response improvement within A six and B 12 treatment cycles*

C, cycle; CR, complete response; PR, partial response, sCR, stringent CR; VGPR, very good PR.
*Adapted from Van de Donk.¹

 Both groups maintained high PFS rates at 12 months:

• PFS rate at 12 months in the 1.3 mg cohort: 91%
• PFS rate at 12 months in the 1.0 mg cohort: 90%

Safety

AEs recorded between cohorts were comparable (Table 1). In both cohorts, infections of any grade were the most recorded AE, followed by neutropenia. In both cohorts, a significant percentage of neutropenia events were Grade 3–4 (50% and 42%, respectively).

Table 1. Adverse events*

Conclusion

Overall, in both iberdomide cohorts, a response improvement of at least 50% was observed. As part of the EMN26 trial, lenalidomide was observed to result in a 31% improvement after 12 cycles. Conclusions across trials cannot be made; however, these results support further investigation of iberdomide vs lenalidomide maintenance post autologous stem cell transplantation in newly diagnosed multiple myeloma.