Paper Details

ABSTRACT

Introduction

Chimaeric antigen receptor T-cell (CAR-T) therapy is an effective, potentially curative treatment for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). In June 2023 the UK’s National Institute for Health and Care Excellence (NICE) approved the use of axicabtagene ciloleucel (axi-cel) for R/R LBCL occurring within 12m of completing first line (1L) chemoimmunotherapy (CIT). We audited the treatment pathway of Welsh pts diagnosed with LBCL between 1 January 2022 and 31 December 2023 to determine if referral for axi-cel was consistent with NICE guidance or if there was inequity of access. The audit was approved by Cardiff and Vale University Health Board (CVUHB) Information Governance and registered on AMaT (Audit Management and Tracking). Digital Health and Care Wales (DHCW) granted access to patient-identifiable data. The audit was undertaken in collaboration with Kite-Gilead who part-funded the project. 

Background

In Wales all pts diagnosed with lymphoma undergo central pathological review by the All-Wales Lymphoma Panel. Clinical and laboratory data are held on Welsh Clinical Portal, a Wales-wide database. Chemotherapy prescribing is done on ChemoCare. It is therefore possible to map the patient pathway and response electronically. The Welsh Index of Multiple Deprivation (WIMD) is the official Welsh Government measure of relative deprivation, based on 8 domains of income, employment, health, education, access to services, housing, community safety and physical environment. We tested whether WIMD scores of 1 (most deprived) to 5 (least deprived) impacted access to or outcome following treatment.

Methods

DHCW provided the list of pts diagnosed with LBCL (ICD 10 code C.83.3) between January 2022 and December 2023 and mapped postcodes to WIMD scores. Eligibility for 2L axi-cel was determined by assessing performance status, 1L therapy, response and timing of relapse with outcomes mapped to WIMD scores. Data collection and analyses were undertaken solely by the SWBMT team. Kite-Gilead had no access to raw data and did not influence interpretation of results.

Results

Three hundred and one pts were diagnosed with LBCL within the review period. Median age was 72 (range 21-100) years with 130 (43%) aged ≥75y. 180 (60%) were male and 192/272 (71%) had an ECOG of 0-1 (29 missing). 212 (70%), 58 (19%) and 31 (10%) pts were treated with curative, palliative or no 1L therapy, respectively. 47/212 (22%) pts treated with curative intent failed 1L CIT within 12m of whom 13 (28%) were referred for and 10 received 2L CAR-T. Reasons for non-referral included 1L failure before CAR-T availability (n=16); palliation due to poor performance status (n=12); CNS relapse (n=3); CAR-T refusal (n=2) or early death (n=1). Three referred pts did not receive CAR-T due to early death from sepsis (n=2) or rapidly progressive disease (n=1). Of the 10 CAR-T recipients 7 are alive (5 in CR) at a median follow-up of 21.7 (13.3-26.6) months and 3 died from disease.

At data cut-off of 31 December 2025, 169 pts (56%) are alive at a median follow-up of 30 (7.2-47.7) months, with 162 (96%) in continuous CR. 3-year OS was 65.9% (95% CI: 57.7-72.8) v 23.7% (15.1-33.5) for pts treated with or without curative 1L intent, respectively (P=0.000). WIMD score did not affect access to (P=0.72) or response following (P=0.45) treatment with curative intent. 

We used US SEER demographics (accessed 23.02.2024) to estimate the potential 2L CAR-T population, assuming most pts <75y would receive 1L treatment with curative intent, a prerequisite for 2L CAR-T in the UK. Our cohort was significantly older with a median age of 72y v 66y with only 57% aged <75y v 71% for SEER. Only 26% failed 1L CIT with curative intent, 85% within 12m, compared with 40% and 75%, respectively, as reported in the literature. The net result was a significantly lower number of early 1L failures (n=47) than was estimated (n=100). 

 
Discussion

Our experience underscores the importance of accurate local demographic and real-world response data when planning services for and evaluating uptake of novel therapies.  Encouragingly, deprivation played no role in access to or response following effective 1L therapy, highlighting the equalising impact of the UK National Health Service which provides treatment free at the point of need, regardless of cost and socioeconomic status. Reasons for non-referral were sound indicating compliance with the NICE-approved treatment pathway.