Background: In the phase 3 IMROZ study (NCT03319667), the addition of isatuximab (ISA) to bortezomib (V), lenalidomide (R), and dexamethasone (d) regimen (VRd) significantly improved the progression-free survival (PFS) (hazard ratio [HR] 0.596; 98.5% confidence interval [CI] 0.406, 0.876; one-sided p=0.0005) in patients (pts) with newly diagnosed multiple myeloma (NDMM) compared to VRd alone. Here, we present the subgroup analysis of the IMROZ trial specifically assessing the efficacy and safety of Isa-VRd versus (vs) VRd among Chinese pts.

Method: IMROZ is a global, randomized, open-label study in pts with NDMM who were ≥65 years old or ineligible for transplant due to comorbidities. An expansion cohort was started in China after the completion of global randomization to enroll a total of around 50 Chinese pts. Pts were randomized 3:2 and stratified by age (<70 years vs ≥70 years), Revised International Staging System (R-ISS, [I or II vs III vs not classified]) and country (China vs non-China) to receive Isa-VRd or VRd. Isa-VRd arm pts received ISA (10 mg/kg intravenously [IV]); both arms received V (1.3 mg/m2 subcutaneously [SC]), R (25 mg orally [PO]) and d (20 mg IV/PO) until disease progression, unacceptable adverse event (AE) or pt decision to stop the study treatment. The primary endpoint was PFS. Key secondary endpoints included complete response (CR) rate; minimal residual disease (MRD) negativity rate (10-5 threshold; next generation sequencing) in CR pts; rate of very good partial response (VGPR) or better; and overall survival (OS). Response and disease progression were assessed by the Independent Review Committee (IRC) based on International Myeloma Working Group (IMWG) criteria. AEs and laboratory parameters were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03.

Results: Fifty pts (12 in global and 38 in expansion cohort) from China mainland were randomized (Isa-VRd: n=31; VRd: n=19). The median age was 67 years (range 51-79). At study entry, most pts presented with R-ISS stage II (74%) or stage III (10%), 18% had high-risk cytogenetics (del[17p], t[4;14], and/or t[14;16]), and 52% had 1q21+. The baseline characteristics were generally balanced between the two arms.

At the data cut-off (September 26, 2023), the median follow-up time was 53.1 months. A clinically significant PFS benefit was shown in favor of Isa-VRd compared with VRd (HR: 0.317; 95% CI: 0.108, 0.928). The median PFS was not reached in Isa-VRd arm vs 37.5 months (95% CI: 19.581, not estimated [NE]) in VRd arm. The estimated 48-month PFS rates were 77.5% for Isa-VRd vs 41.2% for VRd.

For key secondary endpoints, the response rates (≥CR, ≥VGPR) were similar between arms (77.4%, 83.9% in Isa-VRd vs 78.9%, 89.5% in VRd, respectively). The MRD negativity rate in CR pts was numerically higher with Isa-VRd (61.3%) vs VRd (52.6%) (OR: 1.425; 95% CI: 0.449, 4.522), and the 12-month MRD negativity rate was obviously improved with Isa-VRd (54.8%) compared to VRd (15.8%) (OR: 6.476; 95% CI: 1.563, 26.836). Median OS was not reached in either arm, but a favorable trend was observed with an HR of 0.459 (95% CI: 0.154, 1.369).

For safety analysis, the median duration of treatment exposure was 51.6 months with Isa-VRd and 21.9 months with VRd. All pts in both arms experienced at least 1 grade ≥3 treatment-emergent adverse events (TEAEs). The most frequent (≥20% in either arm) grade ≥3 TEAEs included pneumonia (51.6% in Isa-VRd vs 52.6% in VRd), cataracts (41.9% vs 21.1%), thrombocytopenia (22.6% vs 42.1%) and diarrhoea (9.7% vs 31.6%). Discontinuation due to TEAEs occurred in 12.9% of pts in Isa-VRd and 10.5% in VRd. Incidence of serious TEAEs was 90.3% in Isa-VRd and 73.7% in VRd. Deaths due to TEAEs occurred in 0 pts with VRd and 3 pts with Isa-VRd; 2 of which were considered treatment-related (1 pneumonia, 1 sepsis) and 1 was unrelated to treatment (1 COVID-19 pneumonia).

Conclusion: In transplant-ineligible Chinese pts with NDMM, the addition of ISA to VRd improved PFS, which is consistent with the PFS result in the global population and numerically better in terms of HR. Safety profile was generally manageable and consistent with the known safety profile of Isa-VRd. These results demonstrate the consistent and clinically meaningful benefit of Isa-VRd in transplant-ineligible NDMM pts in China, showing the superiority vs standard-of-care treatment.

Disclosures

Gao:Sanofi: Current Employment. Zhao:Sanofi: Current Employment.

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2024
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