IL-1α Blockade May Fight Metastatic Cancer

Targeting key anti-inflammatory molecules may be a novel treatment route for patients with metastatic disease

medwireNews: Blockade of interleukin (IL)-1α could offer hope for patients with advanced, treatment-resistant cancer, suggest preliminary findings for MABp1, a first-in-class human antibody against the molecule.

The research into inhibition of this systemic inflammatory cytokine produced by many tumours represents a “unique contribution” to cancer therapeutics, writes Charles Anthony Dinarello, from the University of Colorado in Denver, USA, in a comment on the study published in The Lancet Oncology.

“The study also provides a rationale for early use of anti-cytokine therapy in cancer and sets the stage for use of anti-cytokine treatment in combination with kinase inhibitors and anti-immunosuppressive treatments”, he comments.

The phase l dose-escalation and expansion study was carried out in 52 patients with 18 different types of metastatic cancer, including non-small-cell lung cancer, colorectal cancer and pancreatic cancer.

The most common side effects possibly linked to MABp1 were proteinuria, nausea and fatigue but none of the patients required dose reduction or delay due to toxicity. There were no treatment-related deaths, with just one possible drug-related case of pneumonia.

The maximum tested dose of 3.75 mg/kg on a 2-week cycle is therefore recommended for the phase II trial, report David Hong, from the MD Anderson Cancer Center in Houston, Texas, USA, and co-authors.

Dual-energy X-ray absorptiometry (DEXA) scans for 30 patients indicated an average lean body mass increase of 1.02 kg between baseline and week 8 of treatment, the majority of whom had a lean body mass gain after just three infusions. Of note, 77% of patients with a lean body mass gain had lost body weight in the 6 months before entering the study, the authors say.

Plasma concentrations of IL-6 – a cytokine induced by IL-1 – measured in 42 patients fell from 12.8 pg/mL at the start of the study to 7.6 pg/mL at week 8 and exploratory analysis of 20 patients with both DEXA and IL-6 data indicated that weight gain was associated with a decrease in IL-6.

Moreover, Response Evaluation Criteria In Solid Tumors for 24 patients indicated that eight had stable disease for at least 3 months, while one patient with K-Ras-mutant colorectal cancer had a partial response. Radiographical evidence of tumour shrinkage was also noted in several patients.

Due to the small number of patients and the range of tumour types included in the study, “meaningful analysis” of survival cannot be performed, David Hong et al say. Nevertheless, they note that patients who gained lean body mass had a non-significant trend towards longer survival than those who did not (19.3 vs 6.6 months).

They hope that two planned clinical trials to investigate MABp1 in colorectal cancer patients may help establish whether treatment is associated with lean body mass gain and whether this outcome is a “robust surrogate for a survival advantage”.


Hong D, Hui D, Bruera E, et al. MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol 2014; Advance online publication 17 April. doi:10.1016/S1470-2045(14)70155-X

Dinarello C. Interleukin-1α neutralisation in patients with cancer. Lancet Oncol 2014; Advance online publication 17 April. doi:10.1016/S1470-2045(14)70164-0

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