Pembrolizumab With R-CHOP in Previously Untreated DLBCL: Sustained, High Efficacy, and Safety With Long-Term Follow-Up.

BACKGROUND

While generally ineffective in relapsed diffuse large B cell lymphoma (DLBCL), immune checkpoint inhibitors (ICIs) may hold greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (PR-CHOP) in a phase I trial of untreated DLBCL, noting responses in 90% of patients (complete response 77%) and a 2-year progression-free survival (PFS) of 83%. We herein report long-term safety and efficacy at 5-year follow up.

PATIENTS AND METHODS

Adult patients with untreated DLBCL or grade 3b follicular lymphoma, intended to receive 6 cycles of R-CHOP were eligible. Patients (N = 30) were treated with pembrolizumab 200 mg IV and R-CHOP in 21-day cycles for 6 cycles.

RESULTS

At median follow up of 4.8 years, 5-year PFS was 71% (CI, 54%-94%) and 5-year overall survival was 83% (CI, 71%-98%). Immune-related adverse events (IRAEs) occurred in 7 (23%) patients (10% grade 3/4). Three IRAEs (rash, thyroiditis, rheumatoid arthritis) occurred beyond 3 months of treatment completion. PD-L1 tumor expression was documented in 19 of 23 (83%) tested patients. None of the 19 patients who had any PD-L1 expression have relapsed, whereas 2 out of the 4 patients with no PD-L1 expression have relapsed.

CONCLUSION

PR-CHOP has led to durable responses in most patients, with the best outcomes in PD-L1-expressing disease. Furthermore, the safety profile was manageable, with no consistent pattern of late events. These data support ongoing strategies incorporating ICIs in frontline DLBCL therapy and confirmation of predictive biomarkers including tumor PD-L1 expression.

Informations de copyright

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Déclaration de conflit d'intérêts

Disclosure A.K.G. reports consultancy/honoraria from Pfizer, Seagen, Janssen Oncology, Millennium, Gilead Sciences, Nurix, Cellectar, Kite/Gilead, Morphosys/Incyte, I-Mab, TG Therapeutics, Pfizer, ADC therapeutics, Amgen, Actinium Pharmaceuticals, Takeda, Epizyme, and Merck; research funding from Merck, Bristol-Myers Squibb, Gilead Sciences, Seagen, Teva, Pfizer, Janssen Oncology, Millennium, IgM, I-Mab, Takeda, and AstraZeneca. B.G.T. reports consultancy at Mustang Bio and Proteios Technology; patents and royalties at Mustang Bio; and research funding from Mustang Bio and BMS/Celgene/Juno. M.S. reports consultancy from AbbVie, Genentech, AstraZeneca, Sound Biologics, Cellectar, Pharmacyclics, BeiGene, Bristol-Myers Squibb, Morphosys/Incyte, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Fate Therapeutics, Lilly, Regeneron, Adaptimmune, MustangBio, TG Therapeutics, and MEI Pharma; research funding from Pharmacyclics, Acerta Pharma, Merck, TG Therapeutics, BeiGene, Celgene, Genentech, MustangBio, AbbVie, Sunesis, Bristol-Myers Squibb, Genmab, and Vincerx. A.J.C reports consultancy from Doximity, Sanofi, Cellectar, AbbVie, Secura Bio, Janssen, Bristol-Myers Squibb/Celgene/Juno; research funding from Bristol-Myers Squibb, Janssen, AbbVie, Celgene, Nektar, Adaptive Biotechnologies, and Harpoon Therapeutics; has stock in Doximity. R.C.L. reports consultancy from Foresight Diagnostics and Seagen; research funding from Cyteir, Bayer, TG Therapeutics, Genentech, Seagen, and RAPT Therapeutics. C.S.U. reports consultancy/honoraria from AstraZeneca, Epizyme, Atara Biotherapeutics, Pharmacyclics, AbbVie, Genentech, Janssen, Incyte, BeiGene, and Lilly; research funding from Pharmacyclics, AbbVie, Lilly, AstraZeneca/MedImmune, Adaptive Biotechnologies, and Gilead. R.D.C. reports consultancy/honoraria from Amgen, Kite/Gilead, Jazz Pharmaceuticals, and Pfizer; research funding from Amgen, Pfizer, Vanda Pharmaceuticals, Servier, Kite, and Incyte; has reported membership on the boards or advisory committees for Autolus and PeproMene Bio; and spouse-owned stock in Seagen. S.D.S. reports consultancy from AstraZeneca, Karyopharm Therapeutics, Kite, Incyte, ADC Therapeutics, BeiGene, AbbVie, Coherus Biosciences (immediate family member), Epizyme, and Numab; research funding from Acerta Pharma/AstraZeneca, Ayala Pharmaceuticals (immediate family member), Bristol-Myers Squibb (immediate family member), Bayer, Denovo Biopharma, Genentech, Ignyta (immediate family member), Incyte, Merck, Portola Pharmaceuticals, BeiGene, ADC Therapeutics, Enterome, Kymera, MorphoSys/Incyte, Nanjing, Portola Pharmaceuticals/Alexion Pharmaceuticals, and Viracta Therapeutics. All other authors declare no competing financial interests.