Related Experiment Video
Updated: Dec 17, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies
Philippe Armand1, Alexander Lesokhin2, Ivan Borrello3
1Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
Abstract:
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.
Insights
Combining PD-1 blockade with CTLA-4 or KIR inhibitors showed activity in classical Hodgkin lymphoma but did not improve efficacy over single-agent PD-1 therapy in other lymphoid malignancies, with higher toxicity observed for one combination.
Area of Science:
- Immunotherapy
- Oncology
- Clinical Trials
Background:
- PD-1 blockade is a key treatment for lymphoid malignancies.
- Some patients do not respond to PD-1 inhibitors alone.
- Combination therapies may enhance anti-tumor activity.
Purpose of the Study:
- To evaluate the safety and efficacy of combining PD-1 blockade with CTLA-4 or KIR blockade.
- To assess outcomes in relapsed/refractory lymphoid malignancies.
Main Methods:
- Phase 1b trial of nivolumab plus ipilimumab (nivo/ipi) or lirilumab (nivo/liri).
- Adult patients with relapsed/refractory classical Hodgkin lymphoma (cHL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM) were enrolled.
- Primary endpoint: safety and tolerability. Secondary endpoints: overall response rate (ORR), complete response rate (CRR), progression-free survival, and overall survival.
Main Results:
- Nivo/ipi and nivo/liri showed activity in cHL with ORRs of 74% and 76%, respectively.
- CRRs in cHL were 23% (nivo/ipi) and 24% (nivo/liri).
- Lower response rates were observed in B-NHL, T-NHL, and no responses in MM. Grade 3-4 adverse events were 29% for nivo/ipi and 15% for nivo/liri.
Conclusions:
- Combination therapy with PD-1 blockade was active in cHL.
- No meaningful efficacy improvement over single-agent PD-1 therapy was observed in the studied lymphoid malignancies.
- Nivo/ipi combination demonstrated higher toxicity than expected.
