TY - JOUR
T1 - A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies
AU - Armand, Philippe
AU - Lesokhin, Alexander
AU - Borrello, Ivan
AU - Timmerman, John
AU - Gutierrez, Martin
AU - Zhu, Lili
AU - Popa McKiver, Mihaela
AU - Ansell, Stephen M.
N1 - Funding Information:
Conflict of interest PA: Paid consultancy from Merck, Bristol Myers Squibb, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo and Miltenyi; research funding (inst) from Adaptive, Affimed, Bristol Myers Squibb, Merck, Otsuka, Roche, Sigma Tau, Tensha, Genentech and IGM; honoraria from Bristol Myers Squibb and Merck. AL: Research funding: Bristol Myers Squibb, Genentech, Janssen, Serametrix; honoraria: Bristol Myers Squibb, Janssen, Novartis, Syndax. IB: Honoraria: Celgene; speakers bureau: Celgene, Onyx; research funding: Bristol Myers Squibb, Celgene. JT: Paid consultancy from Bristol Myers Squibb, Celgene, Celldex therapeutics, Immune Design, and Partner Therapeutics and research funding from Bristol Myers Squibb, Kite Pharma, Merck, and Spectrum. MG: Bayer Health Care Pharmaceuticals, Inc.: Other: Traveling and Lodging-Food and Beverage. E.R. Squibb & Sons, LLC (Bristol Myers Squibb): Consultancy, Other: Travel and Lodging. Incyte Corporation: Consultancy. Pfizer Inc: Consultancy. Merck Sharp & Dohme Corporation: Consultancy, Other: Travel and Lodging. Pharmacyclics LLC, An AbbVie Company: Other: Food and Beverage. LZ: Employment, stock ownership: Bristol Myers Squibb. MPM: Employment, stock ownership: Bristol Myers Squibb. SMA: Research funding (inst) from Bristol Myers Squibb, Affimed, Regeneron, Pfizer, Seattle Genetics, Takeda and AI Therapeutics.
Funding Information:
Acknowledgements PA gratefully recognizes the support of the Leukemia and Lymphoma Society (Scholar in Clinical Research), as well as the Harold and Virginia Lash Foundation. AL acknowledges the support of an MSK Cancer Center Core Grant (P30 CA008748), the MSK Sawiris Foundation, and the Parker Institute for Cancer Immunotherapy at MSKCC. We also are profoundly grateful to all the patients who participated in this study, their families, and the research and clinical staff at all participating institutions. This study was funded by Bristol-Myers Squibb Company.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/3
Y1 - 2021/3
N2 - Simultaneously targeting other pathways could increase the activity of PD-1 blockade in lymphoid malignancies not sensitive to single-agent blockade. We explored the safety and efficacy of combined PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory (R/R) lymphoid malignancies. This phase 1b trial enrolled adult patients with R/R classical Hodgkin lymphoma (cHL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM). Patients received nivolumab plus ipilimumab (nivo/ipi) or lirilumab (nivo/liri) until complete response (CR), progression, or unacceptable toxicity. The primary endpoint was safety and tolerability, while secondary endpoints included overall (ORR) and CR rates (CRR), progression-free and overall survival. Sixty-five patients were treated with nivo/ipi, and 72 with nivo/liri. Twenty-nine percent of patients experienced grade 3–4 treatment-related adverse events with nivo/ipi, and 15% with nivo/liri. In cHL, ORR was 74% for nivo/ipi and 76% for nivo/liri, CRRs were 23% and 24%, respectively. In B-NHL and T-NHL, ORR range was 9–22% and CRR was 0–6%. No patient with MM had an objective response. While both combinations were active in cHL, the toxicity of nivo/ipi was higher than expected from nivolumab alone. These data suggest no meaningful improvement in the efficacy of the combinations over single-agent nivolumab in the diseases studied.
AB - Simultaneously targeting other pathways could increase the activity of PD-1 blockade in lymphoid malignancies not sensitive to single-agent blockade. We explored the safety and efficacy of combined PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory (R/R) lymphoid malignancies. This phase 1b trial enrolled adult patients with R/R classical Hodgkin lymphoma (cHL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM). Patients received nivolumab plus ipilimumab (nivo/ipi) or lirilumab (nivo/liri) until complete response (CR), progression, or unacceptable toxicity. The primary endpoint was safety and tolerability, while secondary endpoints included overall (ORR) and CR rates (CRR), progression-free and overall survival. Sixty-five patients were treated with nivo/ipi, and 72 with nivo/liri. Twenty-nine percent of patients experienced grade 3–4 treatment-related adverse events with nivo/ipi, and 15% with nivo/liri. In cHL, ORR was 74% for nivo/ipi and 76% for nivo/liri, CRRs were 23% and 24%, respectively. In B-NHL and T-NHL, ORR range was 9–22% and CRR was 0–6%. No patient with MM had an objective response. While both combinations were active in cHL, the toxicity of nivo/ipi was higher than expected from nivolumab alone. These data suggest no meaningful improvement in the efficacy of the combinations over single-agent nivolumab in the diseases studied.
UR - http://www.scopus.com/inward/record.url?scp=85087008575&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087008575&partnerID=8YFLogxK
U2 - 10.1038/s41375-020-0939-1
DO - 10.1038/s41375-020-0939-1
M3 - Article
C2 - 32601377
AN - SCOPUS:85087008575
SN - 0887-6924
VL - 35
SP - 777
EP - 786
JO - Leukemia
JF - Leukemia
IS - 3
ER -