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Combining IL-21 and Ipilimumab Resulted in a 5-Year Remission in Metastatic Melanoma

Surabhi Dangi-Garimella, PhD
A single-patient study at the Fred Hutchinson Cancer Research Center found that combining ipilimumab and interleukin-21 (IL-21) in metastatic melanoma eradicated the tumors and the patient remained disease-free 5 years post treatment.
A single-patient study at the Fred Hutchinson Cancer Research Center could be the foundation for a clinical trial to evaluate the combination of a CTLA-4 inhibitor, ipilimumab, and interleukin-21 (IL-21) in metastatic melanoma. The treatment eradicated the tumors and the patient was reported disease-free 5 years post treatment, in a paper published in The Journal of Experimental Medicine.

Patients diagnosed with melanoma, who are refractory to treatment, are the most difficult to treat. Additionally, with immunotherapy agents, the complications associated with the phenomenon of “pseudo-progression” make treatment tricky. As John A. Thompson, MD, a coauthor on the current paper, emphasized at the annual meeting of the National Comprehensive Cancer Network in March this year, healthcare providers need to be aware of this effect when treating patients with immune checkpoint inhibitors.

In the current report, clinicians at the Fred Hutch Cancer Research Center infused a 53-year-old patient with his own antitumor T-cells, which had been stimulated with the immune response stimulator IL-21, followed by a dose of ipilimumab. The patient’s disease had previously failed to respond to either treatment alone. However, within weeks of the combination treatment, the patient’s tumors began to shrink and then completely disappeared. The most encouraging part is that the patient remains in remission at the 5-year mark post treatment.

The authors write that long-term persistence and sustained anti-tumor activity of transferred cytotoxic T-lymphocytes, as well as responses to nontargeted antigens, resulted in mutually beneficial effects of the combination. Combining adoptive cellular therapy with CTLA4 blockade provided sufficient boost to the patient’s immune system to induce long-term remission, compared with both modalities administered serially or individually.

“Combining CTLA4 blockade with the transfer of well-characterized, robust antitumor T cells represents an encouraging strategy to enhance the activity of the adoptively transferred T cells and induce antitumor responses,” Cassian Yee, MD, senior author on the paper said in a statement. Yee now works at The University of Texas MD Anderson Cancer Center in Houston. “This strategy may hold broad promise for ipilimumab-resistant melanomas.”


Chapius AG, Lee SM, Thompson JA, et al. Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient [published online, May 30, 2016]. J Exp Med. doi:10.1084/jem.20152021.

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