Safety and Efficacy of Combination Immunotherapy With Interferon Alfa-2b and Tremelimumab in Patients With Stage IV Melanoma.

04:49 EDT 20th August 2014 | BioPortfolio

Summary of "Safety and Efficacy of Combination Immunotherapy With Interferon Alfa-2b and Tremelimumab in Patients With Stage IV Melanoma."

PURPOSE We tested the hypothesis that the combination of tremelimumab and interferon alfa-2b acting via different and possibly synergistic mechanisms would overcome tumor immune tolerance and lead to significant and durable clinical responses. PATIENTS AND METHODS We conducted a phase II study in which patients were administered tremelimumab 15 mg/kg/course (three cycles [one cycle = 4 weeks]) intravenously every 12 weeks. High-dose interferon alfa-2b (HDI) was administered concurrently, including intravenous induction at 20 MU/m(2)/d for 5 d/wk for 4 weeks followed by maintenance at 10 MU/m(2)/d subcutaneously three times a week for 8 weeks per course. From course 2 onward, HDI maintenance was administered subcutaneously. Results Thirty-seven patients with American Joint Committee on Cancer stage IV (9M1a, 6M1b, and 22M1c) were enrolled. Two patients had previously treated brain metastases. Grades 3 and 4 toxicities included neutropenia (six patients; 17%), diarrhea/colitis (four patients; 11%), liver enzyme increase (four patients; 11%), rash (four patients; 11%), fatigue (15 patients; 40%), and anxiety/depression (five patients; 14%). Response data were available for 35 patients. The best objective response rate (RR; Response Evaluation Criteria in Solid Tumors) by intention to treat was 24% (90% CI, 13% to 36%; four complete responses [CRs] and five partial responses [PRs] that lasted 6, 6, > 12, > 14, > 18, 20, > 28, 30, and > 37 months, respectively). Fourteen patients (38%) had stable disease (SD) that lasted 1.5 to 21 months. The median progression-free survival was 6.4 months (95% CI, 3.3 to 12.1 months). The median overall survival (OS) was 21 months (95% CI, 9.5 to not reached). There was a weak association between therapy-induced autoimmunity and clinical benefits (CR/PR/SD; P = .0059), baseline C-reactive protein (CRP) less than or equal to 2.7× the upper limit of normal and clinical benefits (P = .0494) and improved probability of survival (P = .0032), and baseline lymphocyte count of at least 1,000/μL and response (CR/PR; P = .0183) and clinical benefits (CR/PR/SD; P = .0255). Biomarker associations were not significant after adjustment for multiple comparisons. CONCLUSION HDI can be administered combined with tremelimumab with acceptable toxicity and promising durable antitumor efficacy that warrant further testing in a randomized trial.

Affiliation

University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center Cancer Pavilion, 5150 Centre Ave, Fifth Fl, Pittsburgh, PA 15232; tarhiniaa@upmc.edu.

Journal Details

This article was published in the following journal.

Name: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
ISSN: 1527-7755
Pages: 322-8

Links

PubMed Articles [9825 Associated PubMed Articles listed on BioPortfolio]

Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial.

Pegylated interferon (peginterferon) alfa 2a or 2b plus ribavirin regimens were the standard of care in patients with hepatitis C virus (HCV) infection, but the sustained virological response can be s...

Treatment of indolent primary cutaneous B-cell lymphomas with subcutaneous interferon-alfa.

Interferon-alfa is used in the treatment of primary cutaneous B-cell lymphoma (PCBCL). Therapy with interferon-alfa has thus far been reported solely in case reports and small case series, mostly desc...

Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial.

Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus ribavirin has improved sustained virological response (SVR) in t...

A phase I dose-escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer.

Tremelimumab (CP-675,206) is a fully human monoclonal antibody binding to cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on T cells that stimulates the immune system by blocking the CTLA4-negativ...

A Meta-analysis of efficacy and safety of sublingual immunotherapy on allergic asthma.

To evaluate the efficacy and safety of sublingual immunotherapy(SLIT) in patients with allergic asthma in order to provide reliable evidence for clinical application of SLIT.

Clinical Trials [5071 Associated Clinical Trials listed on BioPortfolio]

Safety and Efficacy of Albumin Interferon Administered Every 4 Weeks in Genotype 2/3 Hepatitis C Patients

This study will evaluate the safety and efficacy of alb-interferon in adults with genotype 2 or 3 chronic hepatitis

Efficacy and Safety of Pegylated Interferon Alfa in Polycythemia Vera

Interferon alfa is an effective treatment of polycythemia vera (PV), but about 20% of patients discontinue their treatment because of side effects and treatment schedule (three times per w...

A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3

To determine the safety and efficacy of two doses of interferon alfa-2a ( IFN alfa-2a ) in combination with zidovudine ( AZT )/zalcitabine ( ddC ) versus AZT/ddC only in patients with HIV...

Does Induction PEG-Intron in Combination With Rebetol Enhance the Sustained Response Rates in Patients With Chronic Hepatitis C

The purpose of this study is to see which of two doses of PEG (polyethylene glycol) interferon alfa-2b in combination with Ribavirin for 48 weeks is more effective at elimination of hepati...

Combination Therapy With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After Therapy With Pegylated Interferon and Ribavirin

To evaluate the efficacy of pegylated interferon alfa-2a 40 kD (PEGASYS) combination therapy with ribavirin (Copegus)given for 24 or 48 weeks in patients with chronic hepatitis C (CHC) vir...

Medical and Biotech [MESH] Definitions

A recombinant alfa interferon consisting of 165 amino acids with arginine at positions 23 and 34. It is used extensively as an antiviral and antineoplastic agent.

A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent.

A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent.

Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).

Monocytes made cytotoxic by IN VITRO incubation with CYTOKINES, especially INTERFERON-GAMMA. The cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.

Search BioPortfolio:
Advertisement
Advertisement

Searches Linking to this Article