P1066: pembrolizumab monotherapy as a first therapy for hodgkin lymphoma is deliverable in older or abvd ineligible patients, does not preclude subsequent therapy, and provides adequate survival.

Topic: 17. Hodgkin lymphoma - Clinical 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 such as reduced performance status, advanced disease and constitutional symptoms. Comorbidities impair capacity to deliver standard HL chemotherapy, with treatment-related mortality as high as 10% with ABVD. The PD1-inhibitor pembrolizumab is highly active in CHL where it is approved as monotherapy for relapsed/refractory disease. We hypothesized the efficacy and toxicity profile may be favourable in an older population, and report the results of an investigator-initiated, prospective, multicentre, single arm trial of pembrolizumab as first treatment for CHL. Aims: To establish the feasibility of pembrolizumab as first therapy for classical Hodgkin lymphoma in an ABVD-unfit population. Methods: Eligible patients had CHL and had to be either considered to be ineligible for frontline ABVD for reasons of fitness or 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 concomitant malignancies were allowed. Treatment consisted of pembrolizumab 200mg 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 (Lugano). Secondary endpoints were safety and time-dependent survival outcomes, and response by LYRIC criteria. The Cumulative index rating scale (CIRS, Salvi et.al) at baseline and post-protocol therapy and survival were recorded. Results: 27 pts were registered between Nov 2018 and Jul 2022. One was registered in error, another withdrew prior to pembrolizumab; both were replaced; 25pts received pembrolizumab. The median age was 77 (range 64-92); 52%/ 48% were male/female; the median CIRS score was 7 [IQR 4-10]; 20% had a 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 were 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 overall survival estimates were 90% (95%CI 67-98) and 83% (95%CI 55-94). 5 patients have died, 12 month survival after developing PD was 77% (95CI: 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%). The most common grade 3/4 related AE was grade 3 elevation of GGT, n=4,16%, which precluded further therapy in 2. One patient discontinued treatment due to grade 3 skin reaction. No other pts discontinued due to toxicity. Of the 8pts who went on to subsequent treatment, 5 had a CR, 2 PR and one had SD. Summary/Conclusion: Pembrolizumab monotherapy 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 as may occur after conventional chemotherapy in elderly patients. Complete response rates in patients receiving subsequent therapy were promising. Further exploration of first therapy with checkpoint inhibitors in frail patients with CHL is warranted.Keywords: Elderly, Immunotherapy, Treatment, Hodgkin’s lymphoma