Real world epidemiological trends in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), England 2014-2021: Preliminary data from the uncover Study group

Abstract Introduction NLPHL is a rare, indolent lymphoma, traditionally considered a subtype of Hodgkin lymphoma (HL), with an excellent prognosis. However, there is a paucity of real-world evidence on the epidemiology and optimal management of NLPHL, which has required international collaboration to address (J Clin Oncol 2024; 42(19):2271-2280). As a result, existing literature is limited by small cohort sizes or patient selection from participating centres only. UNCOVER is a blood cancer health data research programme that utilises the National Cancer Registration Dataset (NCRD). NCRD includes information on all patients diagnosed with cancer in all NHS institutions in England, as a statutory requirement (Int J Epidemiol 2020; 49(1):16–16h). Here, we report epidemiological trends in a large cohort of NLPHL patients registered in the NCRD. Methods Data on all patients in England with a blood cancer diagnosed between Jan 2014-Dec 2021 was obtained from the NCRD. Patients with NLPHL were identified using ICD-O-3 code 9659/3. Crude and age-standardised incidence rates (ASIR) were calculated and adjusted incidence rate ratios (IRR) estimated by Poisson regression for selected patient characteristics. Overall survival (OS) was calculated by Kaplan–Meier and multivariable Cox regression modelling was used to examine independent variables associated with survival outcomes. Relative survival (RS) was estimated using the Pohar-Perme method using life tables of mortality data for England for age, gender, indices of multiple deprivation (IMD), and government region. For cause-specific survival, any blood cancer reported on the death certificate was considered. A two-sided p-value (5% significance level) were used for all statistical tests. All models were adjusted for age, sex, IMD quintile and government region, while the Cox models was also adjusted for ethnicity and Charlson co-morbidity index (CCI). All analyses were conducted using R software, version 4.4.1. Results 1648 patients were registered with NLPHL from Jan 2014–Dec 2021. The median age at diagnosis was 49 years (range 3-93 years). Follow up data for survival was available until July 2023, with a median follow up of 59 months (IQR 38-84months). There was a male preponderance (n=1146, 69.5%) with a male:female of 2.3:1. Most patients were white (n=1147, 69.6%) and had CCI of zero (n=1308, 79.4%). Overall ASIR was 0.39 per 100,000 persons/year. Gender (p<0.001), age (p<0.001), deprivation (p=0.039), ethnicity (p<0.001) and government region (p<0.001) were independently associated with incidence. Adjusted IRR was higher in males (2.3) and in Black and Asian populations (2.1 and 1.3, respectively, vs. the white population). Adjusted IRR increased with age up to 75y (3.72 in 60-75y vs. 0-15y) and then reduced in the >75y age group (2.81). There was marked geographical variation in adjusted IRR, ranging from 0.75-1.21 in the East Midlands and East of England, respectively (v. reference group of London). Adjusted IRR was highest in the most deprived patients (IRR 1.18) and there was no significant difference in IRR in successive calendar years, including the pandemic period (2020-21). OS and RS at 5 years for NLPHL patients in England were similar, at 90.7% (95% CI 89.2-92.36%) and 91.6% (95% CI 89.3-93.7%), respectively. Gender (p=0.02), age (p<0.001) and comorbidity score (p<0.001) were independently associated with OS. Adjusted hazard ratio (HR) increased with age (HR 59.4 in >75y vs. 0-15y) and comorbidity (HR 2.14 in patients with CCI score ³2 vs. CCI 0) and in males (HR 1.47). There was no association between deprivation score and OS (p=0.12). Conclusions Despite the low incidence of NLPHL, access to NDRS datasets has facilitated the collection of a large cohort of unselected patients from all hospitals in England. The racial differences in incidence of NLPHL, is striking. Compared to white patients, IRR was more than double in Black patients and 30% greater in Asian patients. This trend has been described in US data but to our knowledge has never been reported from a UK/European perspective. Despite increased incidence in the most deprived areas, reassuringly survival was not affected by deprivation score. Overall prognosis is excellent, with both OS and RS >90% at 5 years. However, patients over 60y or with multiple comorbidities had a significant survival disadvantage. These data reflect the importance of balancing treatment efficacy with toxicity in this indolent lymphoma.