Kenneth J. C. Lim, Melinda Tan, Ricardo Parrondo, Saurabh Chhabra, Katharine Dooley, Andre De Menezes Silva Corraes, Darin D. Carabenciov, Morie Gertz, L. Y. hwa, Stephens Haily, Prashant Kapoor, Taxiarchis Kourelis, Rahma Warsame, Joselle Cook, Moritz Binder, P. Leif Bergsagel, Udit Yadav, Erin J Wiedmeier-Nutor, Susan Geyer, Sikander Ailawadhi, Rafael D. Fonseca, Shaji Kumar, Αναστασία Ζεκερίδου, Yi Lin
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. ALC peak ≥ 3 × 10 9 /L was identified as a meaningful threshold (AUC = 0.838) to predict for late onset neurotoxicity. An ALC peak ≥ 3 × 10 9 /L conferred a positive predictive value for delayed neurotoxicity of 31% vs a negative predictive value of 98% in patients with ALC peak < 3 × 10 9 /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 2 ) within 1-13 days of symptom onset and all had observable symptom improvement within 1–2 days.