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.

For more information on the top abstracts in multiple myeloma presented at the 65th ASH Annual Meeting and Exposition, selected by our steering committee, check out our recent article.

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.

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).

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*

*Adapted from Van de Donk.1
Adverse events, % (unless otherwise stated)	1.3 mg cohort (n = 40)		1.0 mg cohort (n = 40)
	Grade 1–2	Grade 3–4	Grade 1–2	Grade 3–4
Hematologic
Neutropenia	10	50	10	42
Febrile neutropenia	0	0	0	2
Thrombocytopenia	15	0	10	0
Anemia	5	0	15	0
Lymphopenia	8	2	5	2
Non-hematologic
Fatigue	18	15	18	10
Peripheral neuropathy	15	3	13	0
Rash	20	10	18	3
Infections	55	10	52	13
COVID-19	18	0	30	0
Pneumonia	8	5	3	5

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.