Characteristics and Outcomes of Elderly Patients with Classical Hodgkin Lymphoma (cHL): An Australian Lymphoma Alliance (ALA), and Lymphoma and Related Disease Registry (LaRDR) Study

Introduction: Elderly patients (≥ 61years [y]) with cHL have inferior outcomes compared to their younger counterparts. This group of patients (pts) accounts for 20-25% of the cHL cohort, but they are under-represented in clinical trials and there is no established optimal therapy. Given the heterogeneity of treatment and the paucity of data, we aimed to provide a snapshot of clinical presentations and contemporary front-line management of elderly Australian patients with cHL, as well as to explore patient and treatment factors associated with unplanned hospital admission and survival.

Methods: cHL pts aged ≥61y, diagnosed from 2011-2022, were included. National data from the LaRDR were supplemented by additional detail information on toxicities, hospitalisation and long term survival from 7 Australian centres. Baseline demographics, disease characteristics, front-line management and response were combined from LaRDR and ALA datasets. Statistical analysis was performed on STATA v17. Chi square was utilised for univariate analysis on relevant categorical data relating to hospital admission and a multivariate analysis using logistic regression was built with significant variables identified. Survival analysis was conducted with Kaplan-Meier and univariate analysis was performed with a log-rank test. Clinically relevant parameters were included in a multivariate Cox proportional hazard model.

Results: 195 pts were identified - 123 from ALA, 72 from LaRDR. Baseline characteristics are summarised in Table 1 and 2.

Dataset: ALA and LaRDR (N=195) 91.3% pts commenced on chemotherapy, with anthracycline-based regimens used in 81%. 86.1% pts had ABVD-AVD, 5.7% CHOP, 5.1% PVAG, 3.2% other. Median number of cycles for stage I-II was 2 (range 0-6) and stage III-IV was 6 (range 0-8); 26.2% had radiotherapy. Response to front-line chemotherapy was complete remission (CR) 56.4%; partial remission (PR) 7.2%; stable disease (SD) 1.5%; progressive disease (PD) 7.2%; unknown 27.7%.

Dataset: ALA (N=123) Of the 123 pts, 7 did not commence any therapy, 9 commenced therapy with a palliative intent. Of those who received therapy (n=116); 102 received anthracycline regimens and 66 received bleomycin. Initial therapy was ABVD in 64, AVD in 21, CHOP-like in 7, PVAG in 7, eBEACOPP in 2, miniCHOP in 1, pembrolizumab in 1, unknown 1. A non-anthracycline multiagent regimen was used in 10 pts, single-agent therapy was used in 2. End of therapy response was CR in 71, PR in 10, SD 1, PD in 5 and unknown in 29.

89 unplanned hospitalisations occurred in 58 of 116 pts who received front-line therapy. Of the 102 pts treated with an anthracycline, 53 required an unplanned hospital admission. Pneumonitis occurred in 19 pts, 17 had bleomycin exposure. Of 102 pts treated with an anthracycline, 9 developed a cardiomyopathy. The only factors associated with an unplanned hospitalisation were ECOG status (P=0.01, OR 3.22 [95%CI 1.33-7.81] for ECOG 1 vs 0) and anthracycline use (P=0.04, OR 4.15 [95%CI 1.1-15.64]).

Median follow-up was 2.3y (range 0.01-9.39). Estimated 2y PFS was 64.7% (95% CI 54.8-73.0%), 2y OS 71.3% (95% CI 61.6-78.8%). Estimated 2y PFS for patients who received anthracycline was 70.1% (95% CI 59.5-78.5) versus 33% (95% CI 12.5%-55.6%) for those who did not. The 2y PFS of the 10 pts with cHL from Richter's transformation (RT) was similar to the non-RT cohort at 60% versus 65.1%, P=0.08.

Of pts treated with curative intent, disease relapse occurred in 23/107 at a median of 1.2y (range 0.14-6.41). Fifty pts died, 21 from progressive cHL, 9 from solid tumour, 1 from infection, 11 from other causes, 6 from treatment-related mortality, 2 from secondary treatment complications (cardiomyopathy and acute leukaemia).

Factors associated with an improved OS include receipt of anthracycline (P<0.01), lower ECOG (P<0.01), never smoking (P=0.02), no polypharmacy (P=0.02), receipt of bleomycin (P<0.01), normal albumin (P=0.01). In a multivariate analysis only age (HR 1.11; P<0.01), anthracycline use (HR 0.17; P<0.01) and smoking status (HR 2.19; 95% CI 0.98-4.83 P=0.05) were associated with OS.

Conclusion: This Australian study highlights the characteristics and challenges of treating cHL in elderly patients and emphasises the importance and complications of anthracycline use. Despite these challenges, managing our elderly patients with curative chemotherapy can result in a good PFS/OS and our results are consistent with prior reports.

Lewis:Loxo-Lilly: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Janssen: Honoraria, Patents & Royalties; IQVIA: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria; Novartis: Patents & Royalties; Roche: Consultancy, Honoraria. Cheah:Abbvie: Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hawkes:Beigene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Link: Membership on an entity's Board of Directors or advisory committees; Antengene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol_Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Merck KgA: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Research Funding; Roche: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Regeneron: Speakers Bureau; Specialised Therapeutics: Consultancy; Merck Sharpe and Dohme: Membership on an entity's Board of Directors or advisory committees. Ku:Genor BioPharma: Consultancy; Antengene: Consultancy; Roche: Consultancy; St Vincent's Hospital: Current Employment. Wood:Beigene: Research Funding; Astra Zeneca: Research Funding; Antengene: Research Funding; Amgen: Research Funding; CSL Behring: Research Funding; Bristol-Myers Squibb: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Roche: Research Funding; Gilead: Research Funding; Janssen-Cilag: Research Funding; Sanofi: Research Funding. Cochrane:Beigene: Research Funding.