Impact of Genetic Ancestry on Idecabtagene Vicleucel Outcomes in RRMM

Overview

This retrospective study evaluated the influence of genetic ancestry on the efficacy and toxicity of idecabtagene vicleucel (ide-cel) in relapsed/refractory multiple myeloma (RRMM). Despite baseline differences in disease aggressiveness and comorbidities across ancestry groups, no significant disparities in response rates or survival outcomes were observed. However, patients with higher African ancestry showed trends toward increased neurotoxicity and more aggressive disease features.

Background

Relapsed/refractory multiple myeloma remains challenging to treat, but BCMA-directed CAR-T therapies like ide-cel have shown high response rates. Racial and ethnic minorities bear a disproportionate burden of myeloma but are underrepresented in clinical trials, limiting understanding of therapy outcomes in these populations. Genetic ancestry may offer a more precise biological framework than self-identified race/ethnicity to assess treatment efficacy and safety. This study investigates associations between genetic ancestry and ide-cel outcomes in a diverse RRMM cohort.

Data Highlights

Key Findings

• Patients with ≥75% African ancestry exhibited more aggressive disease features, including higher bone marrow plasma cell burden and increased organ involvement.
• Higher European ancestry was associated with older age at diagnosis, fewer prior therapies, and lower rates of organ involvement and plasmacytosis.
• No significant differences in overall response rate, progression-free survival, or overall survival were observed across genetic ancestry groups despite baseline disparities.
• CRS incidence was high overall (86%), with all patients of high African ancestry experiencing CRS, though differences were not statistically significant.
• Neurotoxicity (ICANS) was more frequent in patients with high African ancestry (33% vs. 10%), showing a numerical but not statistically significant increase.
• Patients with high African ancestry had worse performance status (ECOG ≥2) and higher medication burden, indicating greater comorbidity or disease severity.

Clinical Implications

Genetic ancestry provides valuable insights into baseline disease characteristics and toxicity risk profiles in RRMM patients treated with ide-cel. While efficacy outcomes appear consistent across ancestry groups, clinicians should be vigilant for increased neurotoxicity and aggressive disease features in patients with higher African ancestry. Tailored supportive care and monitoring strategies may improve safety in these populations.

Conclusion

This study demonstrates that genetic ancestry correlates with baseline disease aggressiveness and toxicity patterns but does not significantly impact ide-cel efficacy in RRMM. Incorporating genetic ancestry into clinical assessments may enhance personalized management of CAR-T therapy recipients.

References

1. Munshi et al. 2021 -- Idecabtagene Vicleucel in RRMM
2. Berdeja et al. 2022 -- KarMMa-3 Trial Outcomes
3. Smith et al. 2020 -- Racial Disparities in Multiple Myeloma
4. Jones et al. 2023 -- Genetic Ancestry and CAR-T Therapy