Andre Goy, MD
Chimeric antigen receptor (CAR) T-cell therapies have been commercially available for less than 2 years. In that short time, they have fundamentally improved the prognosis for many patients with lymphoma and leukemia. Although these therapies were initially conceived of and developed as inpatient therapies, interest is growing in extending CAR T-cell therapies to the outpatient setting.
Much depends on progress in overcoming the barriers to outpatient administration, which are considerable. In a 2017 survey, 64% of nearly 400 US-based community oncologists, hematologists, and practice administrators indicated that the logistics of administering and following up with patients would be the most challenging elements of adoption and referral for CAR T-cell therapy. Those surveyed said high toxicities such as cytokine release syndrome (CRS) and neurotoxicities (46%), cost of therapy (29%), and lack of knowledge about CAR T-cell therapy (19%) were chief concerns.1 In addition, 61% said patients should be hospitalized for 1 to 2 weeks based on CAR T-cell toxicities, and 21% said this therapy should be an outpatient procedure (Table)
Two years later, purely outpatient CAR T-cell therapy has been achieved, although not consistently. Oncologists note that the 4-1BB costimulatory domain CAR T-cell therapy is more easily managed than CD28 CAR T-cell therapy. In a 2018 report on delivery and management of CAR T-cell therapy, Teachey et al posited that with the 4-1BB construct, "patients can…be infused with CAR T cells in the outpatient setting and admitted to hospital at the time of fever development."2
Table. Oncologists' Perceptions About Toxicity and Management of CAR T-cell Therapy
AE indicates adverse effects; CAR, chimeric antigen receptor.
Patients infused still require monitoring for up to a month, and “some patients, especially those with a low disease burden, do not require hospital admission at all,” the authors wrote, adding that the "large majority" of CAR T-cell infusions performed at the Fred Hutchinson Cancer Research Center in Seattle, Washington, and Children's Hospital of Philadelphia in Pennsylvania occur in the outpatient setting. For patients treated with CD28 CAR T-cell therapy, initial hospital stays of up to 7 days have proved necessary. CAR T cells “have not fully moved into the outpatient setting,” agreed Andre Goy, MD, MS, chairman and director of the John Theurer Cancer Center in Hackensack, New Jersey. "It’s an ongoing process."
John Theurer has used both tisagenlecleucel (Kymriah), which incorporates the 4-1BB costimulatory domain, and Axicabtagene ciloleucel (axi-cel; Yescarta), which uses the CD28 costimulatory domain. At John Theurer, treatment may begin as outpatient therapy, progressing to hospital admission if warranted by development of CRS-related fever. Physicians generally can wait up to 72 hours, but for Medicare patients, admission is a requirement. Hospital admissions may decline with advances in care, Goy noted. "It will, hopefully, continue more in this direction." Another issue regarding the outpatient setting is that the magnitude and occurrence of toxicities associated with CAR T-cell therapy vary widely across disease types and patient characteristics such as age, comorbidities, and prior therapy. These factors must be weighed in hospital admission decisions.2
Tisagenlecleucel became the first FDA-approved CAR T-cell drug in August 2017, when it was approved to treat patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.3
Axi-cel received FDA approval in October 2017 for adult patients with large B-cell lymphoma who have progressed on at least 2 prior treatments.4
Indications include use in diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. In May 2018, the FDA extended its approval for tisagenlecleucel to include adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.