INTERNATIONAL EXPERT CONSENSUS ON REAL-WORLD CAR T-CELL ELIGIBILITY IN LARGE B-CELL LYMPHOMAS: AN E-DELPHI STUDY
Catherine Thieblemont et al
Université Paris Cité & Assistance Publique des Hôpitaux de Paris APHP, Hôpital Saint-Louis, Paris, France
Background
- Despite robust clinical evidence, regulatory approval and guideline recommendations in second- and third-line settings, disparities persist for referring patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) for chimeric antigen receptor T-cell therapy (CAR T).
- Recent studies estimate only one-third of CAR T-eligible patients are ultimately treated, partly due to uncertainty regarding referral eligibility criteria. Consensus-driven guidance is needed to support equitable, timely referral practices.
- The aim of the study is to identify and characterize consensus on core clinical eligibility criteria to guide referral of patients with r/r DLBCL by community-based physicians to specialized centers for evaluation for CAR T.
Methods
- An e-Delphi study was conducted in accordance with established consensus reporting standards. All study materials, designed in alignment with ACCORD (ACcurate COnsensus Reporting Document) guidelines, received approval from an independent steering committee of clinical experts, and independent institutional review boards.
- A panel of 23 expert hematology and/or oncology clinicians in USA, Canada, UK, France, Germany, and Italy, anonymously responded to statements via a web-based questionnaire (≥75% consensus threshold).
Results
- All (100%, N=23) reported academic research leadership, including guideline development (74.0%) and board memberships (61%), managing a mean (SD) of 63.7 (57.3) patients with LBCL and referring/prescribing CAR T to 22.2 (16.9), in the last 12 months.
- All agreed that CAR T-eligibility is not the same as autologous stem-cell transplant (ASCT)- eligibility, and ASCT-ineligible patients can be considered CAR T eligible; 95.7% agreed that eligibility for CAR T is broader than ASCT.
- Panelists agreed (82.6%) on immediate referral for relapse within 12 months post- or, refractoriness to, first-line treatment. Panelists agreed that response to first-line therapy should be evaluated in all patients after 2-4 cycles using interim PET (82.6%) and that patients with stable disease at these timepoints should be referred (87.0%). All agreed to refer patients with progressive disease after 2-4 cycles, and patients with r/r DLBCL after ≥2 lines of systemic therapy.
- All agreed that age should neither be an absolute contraindication for referral nor, alone, be an absolute exclusion criterion. For patients aged ≥70 years, 87.0% agreed a formal frailty/comorbidity assessment should be prioritized over age alone when determining referral eligibility.
- Performance status (PS) was identified as a core clinical criterion for referral by 91.3%, with automatic referral for an ECOG PS of 0, 1, or 2.
- 82.6% agreed that patients with creatinine clearance above 30 mL/min should automatically be referred, and 78.2% that cardiovascular function is a core criterion.
- Statements not reaching consensus will be re-presented in subsequent Delphi rounds along with the aggregated and anonymized responses from the previous round.
Conclusion
- Round 1 analysis demonstrates robust international expert consensus on referral eligibility for CAR T in patients with r/r DLBCL. The panel strongly endorsed broad eligibility for referral independent of ASCT eligibility, and provided clarity regarding disease status, age, performance, and organ function as core referral criteria.
- These consensus recommendations have the potential to reduce unwarranted variation in referral practices and support more equitable access to CAR T. Final recommendations will be presented at congress.
