Patient Case 2: Development of ICANS on a BCMA-Targeted Bispecific Antibody


Switching focus to the second patient case of multiple myeloma, panelists reflect on the prevalence and impact of ICANS on patients being treated with bispecific antibodies.


Ajai Chari, MD: Let’s move to the next case. Kiah, walk us through this case.

Kiah Purcell, NP: The second case is a 70-year-old woman with relapsed/refractory IgG lambda multiple myeloma post 4 lines of therapy. She’s ISS [International Staging System] stage III at diagnosis, and she has extensive extramedullary disease, vascular deposition of amyloid, and some high-risk cytogenetics. Her past medical history includes peripheral vascular disease, diastolic dysfunction, and deep-vein thrombosis. At the time she started treatment, she had an M-spike [monoclonal protein] of 3.96, a Bence-Jones protein of 205.9 kDa, IgG of 5714 mg/dL, and lambda of … mg/L, and her bone marrow shows 70% to 80% involvement of cells.

This patient was started on teclistamab 1.5 mg/kg with 2 step-up doses. She tolerated step-up dose 1 without symptoms, received step-up dose No. 2, and developed CRS [cytokine release syndrome] and ICANS [immune effector cell-associated neurotoxicity syndrome]. [The next day] she developed a fever and tachycardia with BP [blood pressure] of 107/52 mmHg, a heart rate of 137 beats per minute, a high-fever temperature of 103.5 °F, a respiratory rate of 18 breaths per minute, and oxygen of 93% on room air. At this point, her ICE [immune effector cell-associated encephalopathy] score was 10 of 10, and the ECG [electrocardiogram] showed sinus tachycardia. CRS and infectious work-up were completed. In addition, the patient received antibiotics to rule out any infection or to treat it if she had 1, as well as tocilizumab 8 mg/kg acetaminophen and a normal saline bolus. We saw an improvement in her vitals.

The next day, she had worsening fever and tachypnea as well as tachycardia BP of 119/56 mmHg, heart rate 138 beats per minute, respiratory rate of 22 breaths per minute, a temperature of 102.7 °F , and an oxygen saturation of 94% on room air. Her ICE score was 8 of 10, which is ICANS grade 1. She was given dexamethasone 10 mg IV [intravenous] push started every 12 hours and anakinra 200 mg subcutaneously every 8 hours, acetaminophen, and IV hydration. Infectious work-up came back negative. The next day, her fever had resolved, and her ICE score was 10 of 10. She remained admitted for the first full dose without additional recurrence of CRS or ICANS.

Ajai Chari, MD: Thank you, Kiah. These 2 cases have high marrow burden. This 1 was 70% to 80%; the other 1 was 60%. We all understand that we’d ideally like to make bispecifics completely outpatient, but both cases illustrate the danger of that. Imagine if these patients were at home with a temperature of 103.5 °F, a blood pressure of 80/50 mmHg, and oxygen. If they go to their local ER [emergency department], will the ER staff even know that this is related to the bispecific? Or will they get treated as a patient with sepsis? It’s a reminder that these are very powerful drugs, but we’re early in the community administration of these drugs. We’ll have to work closely as a health care system to move these to outpatient care.

Let me get the ball rolling with this discussion of ICANS. It stands for immune effector cell-associated neurotoxicity syndrome. It occurs because the same cytokines that can be released by T-cell activation can also diffuse into the brain. This can be mimicked by CAR [chimeric antigen receptor] T, where the T cell can move into the CNS and activate monocytes and their macrophages. ICANS can be biphasic. It can be early and coincide with CAR T or CRS. In this case, it was slightly delayed. Symptoms include diminished attention, language disturbances, impaired handwriting or dysgraphia, confusion, disorientation, agitation, aphasia, and somnolence. If more severe, [symptoms include] tremors, seizures, cranial nerve palsies, motor weakness, and incontinence.

Annel, walk us through how ICANS is graded. How we do this ICE score that Kiah referred to?

Annel Urena, RN: We’ll use an ICE tool, which is an immune effector cell-associated encephalopathy test, to see if there are any neurological deficits. We normally ask a few questions. One will do orientation. It’s a graded test, and you’ll ask the year, month, city, and hospital. It’s usually 1 point for each topic that you ask. Then we’ll go into naming, and you’ll have to name 3 objects. You can point to any 3 objects in the patient’s vicinity. The next is following simple commands, such as closing your eyes or sticking out your tongue. Then there’s writing a standard sentence. When these patients are inpatient, the team usually has a log ready for patients to write a general sentence. We compare to see changes in handwriting. Then we’ll have them count backward from 100 by 10. This score will let us know if there’s any impairment or any ICANS, and we’ll grade it accordingly by the score.

In the ASTCT [American Society for Transplant and Cellular Therapy] guidelines for grading of ICANS, grade 1 is a score of 7 to 9; patients can awaken spontaneously. In grade 2, which is a score of 3 to 6, they awaken to voice. But in grade 3, which is 0 to 2, they awaken only to a tactile stimulus. They can have any clinical seizures, focal or generalized, that resolve rapidly or nonconvulsive seizures on EEG [electroencephalography] that resolve with intervention. [They can have] elevated ICP [intracranial pressure] or cerebral edema. For grade 3, there will be focal or local edema on neuroimaging. On grade 4, which has 0 points, the patient is unarousable. They have a depressed level of consciousness. The patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse. They’re normally in a stupor or a coma. They have life-threatening, prolonged seizure greater than 5 minutes or repetitive clinical or electrical seizures without return to baseline in between. Some motor findings for grade 4 will be deep focal motor weakness, such as hemiparesis or paraparesis. With elevated ICP or cerebral edema at grade 4, you’ll see diffuse cerebral edema on neuroimaging, decorticate posturing, sixth cranial nerve palsy, papilledema, or Cushing triad.

Ajai Chari, MD: Thank you, Annel.

Transcript edited for clarity.

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