CancerConnect News:The cancer immunotherapy strategy known as programmed cell death 1 (PD-1) has generated great excitement for its ability to help the immune system recognize and attack cancer. Now according to researcher recently published in The New England Journal of Medicine, PD-1 blockade has demonstrated effectiveness in patients with Hodgkin lymphoma (HL).
Hodgkin’s lymphoma is a cancer of the lymph system. It typically begins in the lymph nodes in one region of the body and then spreads throughout the lymph system. Hodgkin’s lymphoma is one of the more curable cancers with effective treatments available at several stages of disease. First-line treatment of HL typically involves chemotherapy, often with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). One problem with this regimen is the toxicity associated with bleomycin. In fact, older patients may develop bleomycin-related lung toxicity—and some die from this. Some patients with relapsed or refractory HL may also be cured with high doses of chemotherapy and stem cell transplant. For patients that fail stem cell transplant additional treatment options are limited.
Nivolumab belongs to a new class of medicines called PD-1 inhibitors that help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer. Nivolumab works by blocking PD-1. This treatment strategy has previously produced impressive results in melanoma and other cancer types.1-3
Researchers presented the results of a phase 1 clinical study evaluating the PD-1 inhibitor nivolumab among 23 patients with relapsed or resistant HL, most of whom had experienced treatment failure with more than three previous treatment regimens, including stem cell transplant and Adcetris (brentuximab vedotin). In the study Patients received an intravenous infusion of nivolumab every 2 weeks until their lymphoma progressed or they experienced limiting side effects. Nivolumab produced an overall response rate of 87% (20 of 23 patients), with a complete response in four patients (17%) and a partial response in 16 patients (70%). The side effects of nivolumab were modest and similar to those reported with solid tumor cancers.
On the basis of these results, the US Food and Drug Administration has granted nivolumab a breakthrough therapy designation in relapsed HL, and a phase 2 study is under way.
 Robert C, Long GV, Brady B, et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. New England Journal of Medicine [early online publication]. November 16, 2014.
 Topalian SL, Sznol M, McDermott DF, et al. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal of Clinical Oncology [early online publication]. March 3, 2014. doi: 10.1200/JCO.2013.53.0105.
 Study Comparing Opdivo (nivolumab) to Chemotherapy in Treatment Naïve Advanced Melanoma Patients Marks First PD-1 Immune Checkpoint Inhibitor to Demonstrate a Survival Benefit in a Phase 3 Trial [press release]. Bristol-Myers Squibb website. Available at: http://news.bms.com/press-release/study-comparing-opdivo-nivolumab-chemotherapy-treatment-naive-advanced-melanoma-patien&t=635517264951231587.
4.Ansell S, Lesokhin A, Borrello I, et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma. The New England Journal of Medicine. December 6, 2014DOI: 10.1056/NEJMoa1411087