Journal
LEUKEMIA
Volume 35, Issue 3, Pages 777-786Publisher
SPRINGERNATURE
DOI: 10.1038/s41375-020-0939-1
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Funding
- Leukemia and Lymphoma Society
- Harold and Virginia Lash Foundation
- MSK Cancer Center Core Grant [P30 CA008748]
- MSK Sawiris Foundation
- Parker Institute for Cancer Immunotherapy at MSKCC
- Bristol-Myers Squibb Company
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This study examined the safety and efficacy of combining PD-1 blockade with other pathways inhibitors in lymphoid malignancies. While some combinations showed effectiveness in cHL patients, overall, the combinations did not significantly improve upon the efficacy of single-agent nivolumab in the diseases studied.
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.
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