Prompt recognition of acute chimeric antigen receptor T (CAR T)-cell–mediated toxicities is crucial because adequate and timely management can prevent or reverse potential life-threatening complications. In the outpatient setting, patients and informal caregivers have to recognize and report signs and symptoms marking these acute toxicities. This study provides a core set of patient- and caregiver-reported signs and symptoms (outcomes, P/CROs) and definitions of red flags warranting immediate action to include in a daily checklist for support at home, with the goal to make outpatient post–CAR T-cell care safer, optimize patient and caregiver support, and thereby facilitating an early discharge/hospital visit reduction strategy.

We performed a systematic review of phase II/III trials of US Food and Drug Administration–approved CAR T-cell products and selected all common and severe adverse events that could be translated into a P/CRO for inclusion in a two-round modified Delphi procedure. Eleven CAR T-cell–dedicated hematologists from the Dutch CAR T-cell tumorboard representing all treating centers selected P/CROs for inclusion in the core set and defined red flags. The final core set was evaluated with patients and caregivers.

From nine clinical trials, 457 adverse events were identified of which 42 could be used as P/CRO. The final core set contains 28 items, including five signs for measurement via wearables and two signs for caregiver-performed assessments.

This study provides a core set of P/CROs that can serve as a framework for (eHealth) tools that aim to enable patients and caregivers to more effectively recognize and report signs and symptoms of acute toxicities after CAR T-cell therapy, which will enhance safe outpatient treatment monitoring.

This research was made possible by European Union's Horizon 2020 research and innovation program under grant agreement No. 875171, QUALITOP and by the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No. 116026), T2EVOLVE. This Joint Undertaking receives support from the European Union's Horizon 2020 Research and Innovation program and European Federation of Pharmaceutical Industries and Associations (EFPIA).

Conception and design: Anne M. Spanjaart, Elise R.A. Pennings, Milan Kos, Martijn G.H. van Oijen, Inger S. Nijhof, Marie José Kersten

Administrative support: Anne M. Spanjaart, Elise R.A. Pennings, Milan Kos

Provision of study materials or patients: Pieternella J. Lugtenburg, Tom van Meerten, Monique C. Minnema, Marie José Kersten

Collection and assembly of data: Anne M. Spanjaart, Elise R.A. Pennings, Milan Kos, Pim G.N.J. Mutsaers, Tom van Meerten, Jaap A. van Doesum, Monique C. Minnema, Margot Jak, Martijn G.H. van Oijen, Maria T. Kuipers, Inger S. Nijhof, Marie José Kersten

Data analysis and interpretation: Anne M. Spanjaart, Elise R.A. Pennings, Milan Kos, Pieternella J. Lugtenburg, Tom van Meerten, Monique C. Minnema, Suzanne van Dorp, Joost S.P. Vermaat, Marjolein W.M. van der Poel, Martijn G.H. van Oijen, Inger S. Nijhof, Marie José Kersten

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Development of a Core Set of Patient- and Caregiver-Reported Signs and Symptoms to Facilitate Early Recognition of Acute Chimeric Antigen Receptor T-Cell Therapy Toxicities

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.

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Pieternella J. Lugtenburg

Consulting or Advisory Role: Takeda, Roche/Genentech, Genmab, Celgene, Regeneron, Incyte, AbbVie

Research Funding: Takeda (Inst), Servier (Inst)

Travel, Accommodations, Expenses: Celgene

Tom van Meerten

Honoraria: Kite/Gilead

Consulting or Advisory Role: Janssen

Research Funding: Genentech (Inst), Celgene (Inst)

Monique C. Minnema

Consulting or Advisory Role: Janssen-Cilag (Inst)

Speakers' Bureau: Celgene/Bristol Myers Squibb (Inst), Medscape (Inst), Janssen Medical Affairs (Inst)

Joost S.P. Vermaat

Consulting or Advisory Role: Secura Bio

Marjolein W.M. van der Poel

Consulting or Advisory Role: Takeda

Travel, Accommodations, Expenses: Jazz Pharmaceuticals, Daiichi Sankyo

Martijn G.H. van Oijen

Research Funding: Roche (Inst), Nordic Group (Inst), Servier (Inst), Amgen (Inst), Merck (Inst)

Inger S. Nijhof

Consulting or Advisory Role: Janssen, Celgene/Bristol Myers Squibb

Marie José Kersten

Honoraria: Novartis, Kite, a Gilead company, Roche

Consulting or Advisory Role: Novartis, Kite, a Gilead Company, Miltenyi Biotec (Inst), Takeda (Inst)

Research Funding: Kite, a Gilead company (Inst)

Travel, Accommodations, Expenses: Novartis, Kite, a Gilead Company, Roche, Celgene

No other potential conflicts of interest were reported.