UVEA-IXA: Efficacy and safety of ixazomib-based therapy outside a clinical trial setting

The oral proteasome inhibitor ixazomib was approved in combination with lenalidomide and dexamethasone in November 2015 by the U.S. United States Food and Drug Administration (FDA) for patients diagnosed with multiple myeloma (MM) who had received ≥1 prior line of therapy. This approval was based on results collected from the phase III TOURMALINE-MM1 trial (NCT01564537). Between the time of the US approval date and the subsequent European Medicines Agency (EMA) approval in November 2016, ixazomib was made available across Europe via an early access program, UVEA-IXA (Use Via Early Access to Ixazomib).

The program aimed to describe the effect of ixazomib in patients with relapsed/refractory (RR) MM across Europe, outside of a clinical trial setting. Ludwig et al.¹ presented the final results of the program in Clinical Lymphoma, Myeloma and Leukemia. We are pleased to summarize the key findings below.

Study design¹

• Multicenter, observational, noninterventional, longitudinal cohort study
• Split into two phases:

• 1. A retrospective chart review
  2. A 1-year prospective observation period

• The primary objectives were assessing best response and progression-free survival

Results¹

• A total of 309 evaluable patients were enrolled, across 43 sites and eight countries
• The median observation period was 25.5 months
• Baseline patient characteristics at study enrollment are shown in Table 1 and baseline characteristics at treatment initiation are shown in Table 2.

Table 1. Baseline patient characteristics at study enrollment*

*Adapted from Ludwig, et al.1
Characteristic, % (unless otherwise stated)	N = 309
Median age, years	68
Male	54
Prior lines of therapy
1	38
2	43
3	18
Race
White	98
Other	2

Table 2. Baseline patient characteristics at treatment initiation*

ECOG PS, European Cooperative Oncology Group performance scale; ISS, International Staging System. *Adapted from Ludwig et al.1 †Data from 186 patients was unknown.
Characteristic, % (unless otherwise stated)	N = 123†
ECOG PS score
0	24
1	56
2	20
ISS stage
I	35
II	35
III	30
Cytogenetic risk
High-risk	30
No or standard risk	70

Efficacy

• The overall response rate, median progression-free, and median overall survival for all patients and those with ≥1 and ≥2 prior lines of therapy are shown in Figure 1.

ORR, overall response rate; PFS, progression-free survival.
*Adapted from Ludwig et al¹

• A total of 55% of patients received subsequent therapy after ixazomib
  • The median time to the next therapy was 21.4 months

Safety

• Overall, 18% of patients required dose reductions of ixazomib, and 34% dose reductions in lenalidomide
• Ixazomib was discontinued in 80% of patients
• Adverse events (AEs) of any grade were experienced by 64% of patients
• Grade ≥3 AEs were experienced by 37% of patients
• Serious AEs were experienced by 33% of patients
• The most common AEs of any grade are shown in Figure 2

AE, adverse event.
*Adapted from Ludwig et al¹

• An Eastern Cooperative Oncology Group performance scale score ≥2 was associated with an increased risk of progression or death (hazard ratio, 2.085)
  • A performance scale score ≥2 also reduced the chance of achieving an overall response
• There were no statistically significant differences in safety outcomes

Conclusion

Results from the early access program support the use of ixazomib-based therapy outside of a clinical trial setting. Favorable outcomes were observed in patients with ≥1 and ≥2 prior lines of therapy. Treatment was found to be an effective and well tolerated option for patients diagnosed with RRMM.