PEMBROLIZUMAB AS FIRST THERAPY FOR HODGKIN LYMPHOMA IS DELIVERABLE IN OLDER OR ABVD‐INELIGIBLE PATIENTS, ALLOWS SUBSEQUENT THERAPY, AND GIVES ADEQUATE SURVIVAL.

Background: There is no consensus on the optimal treatment of older (≥60y) patients (pts) who develop classical Hodgkin lymphoma (CHL). CHL in this age group is more likely to present with poor risk features, reduced performance status, advanced disease and concomitant illnesses. In this setting, treatment-related mortality may be as high as 10% with ABVD. The PD1-inhibitor pembrolizumab is active in R/R CHL. We hypothesized the efficacy and toxicity profile may be favourable in this population. We report the results of an investigator-initiated, prospective, multicentre, single-arm trial of pembrolizumab monotherapy as first treatment for CHL. Methods: Eligible patients had to be either considered to be unfit for frontline ABVD for reasons of comorbidity or be aged ≥65; have an ECOG < 3, adequate organ function (including platelets ≥75, neutrophils ≥1.0), GFR ≥ 30mL/min. Key exclusions were autoimmune disease or infection at baseline, or disease that could be completely irradiated. Low-risk other malignancies were allowed. Treatment consisted of pembrolizumab 200 mg q21d, up to 35 cycles. Cessation of treatment for pts achieving CR was optional, and retreatment on progression was permitted. The primary endpoint was response rate. Secondary endpoints were safety and time-dependent survival outcomes. We recorded cumulative index rating scale (CIRS) at baseline and post-protocol therapies. Results: 27 pts were registered. One was registered in error, another withdrew prior to pembrolizumab; both were replaced and 25pts received treatment. The median age was 77 (range 64–92); 52%/48% were male/female; the median CIRS was 7 (IQR 4–10); 20% had an ECOG performance score of 2. 92% had stage III/IV disease, 48% had B symptoms and 56% had extranodal disease. A median of 11 cycles was delivered (range 1–35). 18/25 (72%) pts responded, 8 (32%) had a CR. The median DOR was 10.6 months (95% CI 3.4-NE). After a median follow-up of 25.1months, the 12-month and 24-month OS estimates were 90% (95% CI 67–98) and 83% (95% CI 55–94). 5 pts died, 12-month survival after PD was 77% (95% CI: 44, 92). There were no treatment-associated deaths. The most common any-cause adverse event (AE) was grade 1/2 arthritis n = 7, 28% and pruritis (24%). 8 pts (32%) had a gr 3/4 event, which precluded further therapy in 2. Of the 8pts who went on to subsequent treatment, 5 had a CR, 2 PR, and one had SD. Conclusion: Pembrolizumab was feasible in an ABVD-unfit, elderly, and significantly comorbid cohort of patients with advanced CHL. Despite the characteristics of the patient group and the development of immune-mediated AEs in some, there were no treatment-related deaths that may occur after conventional chemotherapy in elderly patients. Complete response rates in patients receiving subsequent therapy were reassuring. Further exploration of first therapy with checkpoint inhibitors in frail patients with CHL is warranted. Encore Abstract—previously submitted to EHA 2023 The research was funded by: MSD Keywords: Hodgkin lymphoma, immunotherapy Conflicts of interests pertinent to the abstract M. J. Dickinson Consultant or advisory role: MSD Honoraria: MSD Research funding: MSD L. Berkahn Stock ownership: Beigene