KEY TAKEAWAYS
- The CARTITUDE phase 1,2 and 3 trials aimed to outline the incidence, presentation, and handling of CNP in patients treated with cilta-cel within CARTITUDE studies.
- The results revealed that nurses need to recognize and treat CNP promptly, ruling out infection or myeloma progression as potential causes.
Treatment using the chimeric antigen receptor (CAR)-T cell therapy cilta-cel led to profound and enduring responses in relapsed/refractory multiple myeloma (RRMM) patients in CARTITUDE-1.
Additionally, in CARTITUDE-4, it demonstrated enhanced progression-free survival compared to standard-of-care in lenalidomide-refractory MM patients with 1 to 3 prior lines of therapy (HR, 0.26, P<0.0001). Neurotoxicities, such as cranial neuropathies (CNPs), have been reported in patients undergoing CAR-T cell therapies, highlighting the importance for nurses to be knowledgeable about their presentation and management.
Leslie Bennett and the team aimed to examine the occurrence, symptoms, and treatment of CNPs in patients treated with cilta-cel within CARTITUDE trials.
In the CARTITUDE studies (CARTITUDE-1, CARTITUDE-2 – cohorts A, B, and C, and CARTITUDE-4), patients were administered cilta-cel via infusion. CNP were graded using the NCI-CTC Adverse Event reporting guidelines. A typical diagnostic evaluation for CNP cases involved cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) at the investigator’s discretion.
The results revealed that CNPs were observed in 21 out of 332 (6.3%) patients treated with cilta-cel. The median time to symptom onset was 22 days (range: 17-101 days), with 81% occurring around day 22 ± 5. Predominantly male patients (81%) experienced CNPs, mostly presenting as grade 2 cases; however, 3 patients had grade 3 CNP. Cranial nerve (CN) VII was involved in all cases, with 2 cases additionally involving CN V (both grade 3) and 1 involving CN III (grade 3). CNPs were noted to be bilateral in six cases and unilateral, predominantly left-sided, in 15 cases.
About 12 patients experienced simultaneous neurological symptoms or other neurotoxicities, 1 patient had prior grade 2 immune effector cell–associated neurotoxicity syndrome (ICANS), and no patients with CNP exhibited movement or neurocognitive toxicity, such as parkinsonism.
No evidence of infectious or malignant etiology was found through cerebrospinal fluid (CSF) analysis (n=14) or brain MRI (n=17), although facial nerve enhancement was observed in seven MRI cases. Treatment for CNP included corticosteroids, with a median duration of 13 days. CNP resolved in 19 out of 21 patients, even in grade 3 cases, with a median resolution duration of 66 days.
The study concluded that following cilta-cel treatment in the CARTITUDE program, CNP predominantly presented as low grade and typically resolved with a short course of corticosteroid treatment in the majority of patients.
The incidence of CNP was not correlated with prior grade ≥2 cytokine release syndrome (CRS) or any-grade ICANS. Nurses must be adept at identifying and treating CNP, including conducting a comprehensive differential diagnosis to eliminate infection or myeloma disease progression as potential causes.
The trial was sponsored by the Janssen Research & Development, LLC.
Source: https://ons.confex.com/ons/2024/meetingapp.cgi/Paper/15574
Clinical Trials: https://clinicaltrials.gov/study/NCT03548207
https://clinicaltrials.gov/study/NCT04133636
https://clinicaltrials.gov/study/NCT04181827
Bennett L, Kruyswijk S, Sidana S, et al. (2024). “Incidence and Management of Cranial Nerve Impairments in Patients With Multiple Myeloma Treated With Ciltacabtagene Autoleucel in CARTITUDE Studies.” Presented at ONS 2024 (I21)
