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<p>We examined the clinical course and risk factors for late onset neurotoxicities, including nerve palsies (IEC-NP) and parkinsonism (IEC-PKS), in patients with relapsed/refractory multiple myeloma (RRMM) treated with ciltacabtagene autoleucel (cilta-cel) in standard-of-care practice (SOC). Among 235 RRMM patients who received cilta-cel, 15 (6.4%) developed IEC-NP and 9 (3.8%) developed IEC-PKS with one patient developing both. Pre-infusion, patients with age &gt;75 years, bone marrow plasma cells ≥20%, or involved free light chain ≥20 mg/dL had increased odds of IEC-PKS. Post-infusion, patients who developed ICANS, received higher cumulative steroid doses or received &gt;1 dose of tocilizumab also had increased odds of IEC-PKS. High peak absolute lymphocyte count (ALCpeak) was a statistically significant predictor on univariate and multivariate analysis for IEC-NP and IEC-PKS. ALC<sub>peak</sub> ≥ 3 × 10<sup>9</sup>/L was identified as a meaningful threshold (AUC = 0.838) to predict for late onset neurotoxicity. An ALC<sub>peak</sub> ≥ 3 × 10<sup>9</sup>/L conferred a positive predictive value for delayed neurotoxicity of 31% vs a negative predictive value of 98% in patients with ALC<sub>peak</sub> &lt; 3 × 10<sup>9</sup>/L. All IEC-NP patients received steroid +/- IVIG; 87% had complete resolution of their cranial neuropathies (median 57 days). Four patients with IEC-PKS received cyclophosphamide (1.5–2 g/m<sup>2</sup>) within 1-13 days of symptom onset and all had observable symptom improvement within 1–2 days.</p>

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Clinical course, risk factors and mitigating strategies for Immune effector cell-associated late onset neurotoxicities after ciltacabtagene autoleucel CAR-T in multiple myeloma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月31日

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  • Kenneth J. C. Lim,
  • Melinda Tan,
  • Ricardo Parrondo,
  • Saurabh Chhabra,
  • Katharine Dooley,
  • Andre De Menezes Silva Corraes,
  • Darin Carabenciov,
  • Morie Gertz,
  • Lisa Hwa,
  • Stephens Haily,
  • Prashant Kapoor,
  • Taxiarchis Kourelis,
  • Rahma Warsame,
  • Joselle Cook,
  • Moritz Binder,
  • P. Leif Bergsagel,
  • Udit Yadav,
  • Erin Wiedmeier-Nutor,
  • Susan Geyer,
  • Sikander Ailawadhi,
  • Rafael Fonseca,
  • Shaji Kumar,
  • Anastasia Zekeridou,
  • Yi Lin

摘要

We examined the clinical course and risk factors for late onset neurotoxicities, including nerve palsies (IEC-NP) and parkinsonism (IEC-PKS), in patients with relapsed/refractory multiple myeloma (RRMM) treated with ciltacabtagene autoleucel (cilta-cel) in standard-of-care practice (SOC). Among 235 RRMM patients who received cilta-cel, 15 (6.4%) developed IEC-NP and 9 (3.8%) developed IEC-PKS with one patient developing both. Pre-infusion, patients with age >75 years, bone marrow plasma cells ≥20%, or involved free light chain ≥20 mg/dL had increased odds of IEC-PKS. Post-infusion, patients who developed ICANS, received higher cumulative steroid doses or received >1 dose of tocilizumab also had increased odds of IEC-PKS. High peak absolute lymphocyte count (ALCpeak) was a statistically significant predictor on univariate and multivariate analysis for IEC-NP and IEC-PKS. ALCpeak ≥ 3 × 109/L was identified as a meaningful threshold (AUC = 0.838) to predict for late onset neurotoxicity. An ALCpeak ≥ 3 × 109/L conferred a positive predictive value for delayed neurotoxicity of 31% vs a negative predictive value of 98% in patients with ALCpeak < 3 × 109/L. All IEC-NP patients received steroid +/- IVIG; 87% had complete resolution of their cranial neuropathies (median 57 days). Four patients with IEC-PKS received cyclophosphamide (1.5–2 g/m2) within 1-13 days of symptom onset and all had observable symptom improvement within 1–2 days.