In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e14555-e14555
Abstract:
e14555 Background: Anti-PD1 have produced significant antitumor activity in multiply malignancies, however, resistance to anti-PD1 is becoming increasingly apparent in recent years. Low-dose decitabine, a classical DNA hypomethylating agent, was shown to boost effector T cell function and trigger a T cell-mediated response. This phase I study was designed to assess the safety, immunological effects and antitumor activity of this novel combination in patients with advancedanduntreated lymphomas and solid tumors. Methods: Patients were treated with decitabine (10mg/d on day 1-5) and anti-PD1 (2-3mg/kg, day 8) per 3 weeks. Modified salvage regimens (lymphoma: COP; solid tumors: platinum-based chemotherapy) were allowed to be intermittently inserted for patients with aggressive progression. Treatment continued unless disease progression or severe toxicity. Safety was assessed by CTCAEv4.0, and response by standard international criteria. The phenotype and activity of T cells were periodically measured in peripheral blood by flow cytometry. Results: Todate, 11 patients with heavily treated history and refractory bulky lesions have been enrolled, including 8 with lymphomas (7 NHL, 1 HL resistant to anti-PD1) and 3 with metastatic solid tumors (2 gastric cancers, 1 esophageal cancer) failure to anti-PD1. 5 patients (45%) experienced Grade ≥ 3 toxicities, with 1 taken off due to toxicity, and 1 died of asystole during the term of severe cytokine release syndrome (CRS). The common events of leukocytopenia and CRS were prominent features of anti-PD1 plus decitabine. 9 patients were evaluable for response, 1 HL obtained complete response, 3 NHL and 3 solid tumors achieved partial response, and 2 NHL had stable disease with nearly 20% shrinkage. The frequency of interferon-γ-producing CD8+ T cells in the total CD3+ population was largely increased after anti-PD1 plus decitabine infusion. Conclusions: Decitabine augmented the pro-inflammatory effects of anti-PD1 characterized by systemic inflammation response, and further improved antitumor activity of anti-PD1. Clinical trial information: NCT02961101. Clinical trial information: NCT02961101.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.e14555
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
