Monitoring of Infectious Disease After CAR T-Cell Therapy

Clinical Pearl: Close monitoring of patients in the immediate post–CAR T-cell therapy setting is imperative for appropriate management of prophylaxis, as a patient may develop delayed/recurrent cytopenias.

Mrs. Hernandez is a 71-year-old female diagnosed with multiple myeloma who received idecabtagene vicleucel (ide-cel) for relapsed/refractory disease. By day 3, she developed cytokine release syndrome (CRS) grade 1, which continued through day 4 when she was found to have immune effector cell-associated neurotoxicity syndrome (ICANS) grade 1 with immune effector cell (ICE) score 8/10. She was treated with IV tocilizumab 8 mg/kg and dexamethasone 10 mg. CRS and ICANS resolved on day 5. Due to febrile neutropenia, Mrs. Hernandez had an infectious disease workup and was started on empiric IV antibiotics of vancomycin and cefepime. Blood culture, urine culture, and chest x-ray were negative. She was given growth colony-stimulating factors (G-CSF) starting on day 3 to keep her absolute neutrophil count (ANC) > 1, and her hemoglobin and platelets were transfused as needed. She was discharged in stable condition on day 8 with biweekly follow-up with the advanced practice provider (APP) for count checks.

Day 9

Mrs. Hernandez presented to the outpatient clinic constitutionally well without any complaints. Her counts were sufficient without indication for replacement. The APP reviewed her prophylactic medications and instructed her to continue:

• Valacyclovir 500 mg orally daily for up to a year for viral prophylaxis
• Pentamidine IV 4 mg/kg every 21 days for up to a year and until CD4 counts are > 200 cells/μL for PJP prophylaxis
• Levetiracetam 500 mg orally daily until day 30, when she will taper to 500 mg daily for 3 days then stop
• Levaquin 500 mg daily until day 14 for bacterial prophylaxis
• Fluconazole 200 mg PO daily until day 14 for fungal prophylaxis so long as her ANC remains > 1 without G-CSF support

Day 14

Mrs. Hernandez returned for monitoring and was noted to have cytopenias and concern for cytomegalovirus (CMV). She received one dose of filgrastim-sndz, and due to persistent replacement dependent neutropenia, her levofloxacin and fluconazole were renewed for 7 more days.

Day 17

She remained asymptomatic, and her ANC improved without needing further GCSF. Levaquin and fluconazole were discontinued.

Day 21

She was more cytopenic, necessitating a dose of G-CSF and platelet transfusion. Levofloxacin and fluconazole were restarted. She was seen by infectious disease due to rising CMV levels and started on maribavir 400 mg daily. She was instructed to continue fluconazole, but should the neutropenia persist, her regimen could be changed to posaconazole 300 mg daily, which would have mold coverage.

Day 24

She was noted to have a nice neutrophil recovery.

Day 28

She became neutropenic again and required another dose of G-CSF. Levofloxacin and fluconazole scripts were extended.

Day 35

She was noted to have normalization of neutrophil counts.

Day 42

Her neutrophil counts remained normal without G-CSF support, and levofloxacin and fluconazole were stopped.

Managing Neurotoxicity Associated With CAR T-Cell Therapy

Clinical Pearl: Prompt identification and treatment of neurotoxicity leads to improved outcomes for patients with ICANS.

Mrs. Barnett is a 56-year-old female with multiple myeloma that was diagnosed in 2015. She underwent several lines of therapy including a clinical trial with bispecific antibody. She was found to have progressive disease with new and increased FDG avid lesions and was considered for ciltacabtagene autoleucel (cilta-cel). She was admitted for CAR T-cell infusion and was started on valganciclovir for history of cytomegalovirus (CMV) viremia.

Her hospital course was unremarkable except for close CMV monitoring. The presence of CMV levels was determined to be related to low blood counts. She was discharged on day 10 in stable condition but was readmitted to the hospital on day 13 for fever. She was determined to have grade 1 cytokine release syndrome (CRS) and was started on empiric antibiotics. Notably, her C-reactive protein (CRP) and ferritin increased, supporting CRS. CT of the head showed a new subcortical hypodensity in the left posterior temporal lobe. MRI of the brain showed vasogenic edema in the left occipital lobe without enhancing lesions. Mrs. Barnett was thought to have posterior reversible encephalopathy syndrome (PRES), and the advanced practice provider consulted neuro-oncology. She did not have any neurologic symptoms. Her immune effector cell (ICE) score was 10/10, but because she had presence of vasogenic edema, her immune effector cell-associated neurotoxicity syndrome (ICANS) score was 3. She was treated with one dose of IV tocilizumab 8 mg/kg intravenously for treatment of CRS and IV dexamethasone 10 mg for treatment of ICANS. Her CRS resolved on day 14. She was monitored closely for worsening neurologic symptoms.

On day 18, she was noted to have parkinsonism-type symptoms with apraxia and cogwheel rigidity of her right wrist. Her ICE score remained 10/10. She was treated with high-dose vitamin C and E for neuroprotection. Repeat MRI of the brain showed improvement in the cerebral edema, which resulted in resolution of ICANS. Her neurologic symptoms were treated with daily dexamethasone 10 mg, and the symptoms persisted until day 20 when she was discharged. At that time, neuro-oncology instituted a steroid taper so long as her symptoms did not return. She was discharged in stable condition and with resolution of neurologic symptoms.