Long-term efficacy and safety of pembrolizumab with R-CHOP as first-line therapy for DLBCL.

person Carrie Ho Fred Hutchinson Cancer Center, Seattle, WA info_outline Carrie Ho, Jonathan R. Fromm, Min Fang, Brian G. Till, Mazyar Shadman, Andrew Cowan, Ryan C. Lynch, Vicky Wu, Jenna M. Voutsinas, Heather A. Rasmussen, Katharine Blue, Chaitra Shankar Ujjani, Andrei R. Shustov, Ryan Daniel Cassaday, Ajay K. Gopal, Stephen Douglas Smith

Authors person Carrie Ho Fred Hutchinson Cancer Center, Seattle, WA info_outline Carrie Ho, Jonathan R. Fromm, Min Fang, Brian G. Till, Mazyar Shadman, Andrew Cowan, Ryan C. Lynch, Vicky Wu, Jenna M. Voutsinas, Heather A. Rasmussen, Katharine Blue, Chaitra Shankar Ujjani, Andrei R. Shustov, Ryan Daniel Cassaday, Ajay K. Gopal, Stephen Douglas Smith Organizations Fred Hutchinson Cancer Center, Seattle, WA, Division of Hematopathology, University of Washington, Seattle, WA, Division of Medical Oncology, University of Washington, Seattle, WA, Seagen, Inc., Bothell, WA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Merck, U.S. National Institutes of Health Background: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) represents the historical 1 st line treatment standard for DLBCL but fails to cure about 1/3 of patients. While generally ineffective in relapsed DLBCL-NOS, checkpoint inhibitors may have greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus RCHOP, noting objective responses in 90% of patients (CR 77%) and a 2-year progression-free survival (PFS) of 83%. We now report 5 year follow up of our study. Methods: Patients age > 18 with untreated DLBCL or grade 3b follicular lymphoma, intended to receive 6 cycles of R-CHOP, were eligible. Pembrolizumab 200 mg IV with R-CHOP was given in 21-day cycles for 6 cycles. For this updated analysis, progression and survival events, and immune-related toxicities, are reported. Additionally, prognostic factors including tumor PD-L1 expression (Qualtek/Merck) were re-analyzed. Results: 30 patients were treated (13/30 with IPI 3-5). Median follow up is now 4.8 years (95% CI, 4.5-5.4). Since our initial report (Smith BJH 2019) we have observed 1 additional relapse (alive after CAR-T therapy) and 2 deaths in remission (1 urothelial carcinoma, 1 respiratory failure in the setting of progressive ILD). 5-year PFS is 71% (CI, 54-94%) and 5-year overall survival 83% (CI, 71-98%). During the study period and at long term follow up, there were 8 total immune-related adverse events (IRAEs) among 7 patients (23%) (Table). Four were treatment-emergent AE (occurred within 90 days of completing treatment): grade 1 hyperthyroidism, grade 2 hyperthyroidism, grade 3 pneumonitis, and grade 3 rash. There were 4 late IRAEs: colitis, paraneoplastic pemphigus, rheumatoid arthritis, and Graves’ disease, occurring at 3, 5, 8, and 46 months after completing treatment, respectively. PD-L1 tumor expression was documented in 19 of 23 (83%) tested patients. At long-term follow up, none of the 19 patients who had any PD-L1 expression have relapsed. Two out of the 4 patients with no PD-L1 expression have relapsed. On univariate analysis, PD-L1 H-score >0 (p<0.0001) was associated with improved PFS. Conclusions: At 5 year follow-up, pembrolizumab plus R-CHOP has led to durable responses in most patients with the best outcomes in PDL1-expressing disease. Furthermore, the safety profile was manageable, with a low rate of grade 3 or higher IRAEs (10%) and no consistent pattern of late events. These data support ongoing strategies incorporating PD-1/PDL-1 inhibitors in 1st line DLBCL therapy and confirmation of predictive biomarkers including tumor PD-L1 expression. Clinical trial information: NCT02541565. IRAEs. Treatment-emergent IRAE Any Grade, N (%) Grade >= 3, N (%) Hyperthyroidism 2 (6.7) 0 Rash 1 (3.3) 1 (3.3) Pneumonitis 1 (3.3) 1 ((3.3) Late IRAE Rash (paraneoplastic pemphigus) 1 (3.3) 1 (3.3) Colitis 1 (3.3) 0 Hyperthyroidism (Graves’ Disease) 1 (3.3) 0 Rheumatoid arthritis 1 (3.3) 0

Clinical