Earlier Patient Communication Needed to Adequately Address Barriers to CAR T-Cell Therapy in the Second Line

Clinical Pearl: Even medically suitable patients may experience barriers to CAR T-cell therapy. Although increasing product manufacturing will be one way to improve access to treatment, understanding the other barriers that currently exist is important for those who provide care to patients with multiple myeloma.

Mr. Fitzgerald is a 62-year-old man who was first diagnosed with multiple myeloma when he presented to his primary care physician with generalized bone pains and worsening fatigue. His bloodwork showed renal failure, hypercalcemia, and anemia, and he was urgently sent to the emergency room. Upon further workup, he was diagnosed with stage 2 lambda light chain multiple myeloma, with gain of 1q and complex cytogenetics. He was started on therapy with bortezomib and dexamethasone and then switched to lenalidomide, bortezomib, and dexamethasone (RVd). Because imaging showed a large destructive lesion of the left acetabulum, he also received 3,000 cGy of radiation to the lesion. He eventually went on to receive a successful autologous stem cell transplant, and he is now being seen in follow up while on lenalidomide maintenance therapy. However, he notably has new evidence of measurable disease, as his free light chains are increasing.

In thinking about other treatment options, you reviewed Mr. Fitzgerald’s overall medical history. He has hypertension and hypothyroidism but is otherwise healthy. Since his transplant, his performance status has improved, and he has become more active. In the absence of other comorbidities, you feel Mr. Fitzgerald would be a good candidate for ciltacabtagene autoleucel (cilta-cel) in second-line treatment.

After you provided Mr. Fitzgerald an overview of CAR T-cell therapy, he shared with you that he is concerned about the cost of therapy. In addition, he lives 2. 5 hours away from the nearest CAR T-cell therapy center, which worries him. After his unexpected diagnosis and hospitalization, he and his family feel financially strained and are wary of more expensive treatment.

You listened to Mr. Fitzgerald and agreed that these were valid concerns. You explained to him that CAR T-cell treatment teams are multidisciplinary and include case managers, social workers, and other support staff who can help navigate patient assistance programs. In many cases, patients can get coverage for non-medical costs such as lodging, transportation, and food. Additionally, there may be an opportunity for increased telemedicine visits to reduce travel burden. The best way to know is to talk directly to the team. Thus, if he is interested in the therapy, earlier referrals are generally better, especially since other logistics such as appointment availability and insurance approvals can take additional time. Mr. Fitzgerald agreed to a referral in order to talk more with the CAR T-cell team to ensure this therapy would be the right decision for him.

Reference

1. Hoffmann MS, Hunter BD, Cobb P, et al. Overcoming barriers to referral for chimeric antigen receptor T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma. Transplant Cell Ther. 2023;29(7):440-448.

Proactive, Guideline-Based Side-Effect Management Is Key to Overall Outcomes for CAR T-Cell Therapy

Clinical Pearl: Advanced practitioners (APs) play an integral role on teams that deliver cellular therapy. As more patients become eligible for treatment with CAR T-cell treatment, it is crucial that APs remain astute in the identification and management of toxicities, as well as longer-term sequalae.

Mrs. Greenberg is a 57-year-old woman with relapsed/refractory IgA kappa multiple myeloma, who had previously received three lines of therapy and is now post-treatment with ciltacabtagene autoleucel (cilta-cel). Her hospital course was complicated by grade 2 cytokine release syndrome (CRS) and grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS). 

She first developed grade 1 CRS on day 5 after treatment, which was manifested by a fever to 101°F. Per institutional protocol, she was given one dose of intravenous (IV) tocilizumab (8 mg/kg). On day 7, she had recurrent fever of up to 101.3°F and new hypoxia. She was treated for grade 2 CRS and again received 8 mg/kg of IV tocilizumab along with IV dexamethasone (10 mg x 1). The next evening, on day 8, her routine ICE Score had dropped to 7/10, and she received IV dexamethasone (10 mg) for grade 1 ICANS. Despite this intervention, she was noted to have worsening confusion and word-finding difficulties on day 9, consistent with grade 2 ICANS. As such, she continued on dexamethasone but at a more frequent dosing. Her prophylactic antiepileptic medication dose was increased per guidelines. Neurology was consulted, and a spot EEG was performed, which did not show any epileptic activity. A non-contrast head CT was obtained and did not show any acute hemorrhage, edema, or large vessel infarct. Her steroids were continued until her ICANS improved, and she was able to taper off steroids entirely by day 13, without recurrence of either CRS or ICANS.

Mrs. Greenberg was discharged from the hospital with a plan for follow-up in the infusion clinic at least twice weekly with the cellular therapy team. Mrs. Greenberg is now 24 days post-treatment and has presented for routine follow-up. Upon arrival, she was febrile (101.3 F). Her heart rate was 109 bpm, oxygen saturation was 90% on room air, and her respiratory rate was 18. She reports feeling weak and has a nonproductive cough. On medication review, she had been taking 10 mg of lisinopril orally (PO) daily, 800 mg of acyclovir PO twice daily, 300 mg of posaconazole PO daily, 1,500 mg of atovaquone daily, and 1 g of levetiracetam PO twice daily. Bloodwork showed the following:

Because of her symptom report, you also order a chest x-ray that showed a new consolidation in the left lower lung base. Blood cultures were sent, and urinalysis was negative.