Three case reports published in the New England Journal of Medicine demonstrate the promise of cancer immunotherapy in gray zone lymphoma, a rare subtype that mixes characteristics of Hodgkin and Non-Hodgkin forms of the disease. In one case from the
Three case reports published in the New England Journal of Medicine demonstrate the promise of cancer immunotherapy in gray zone lymphoma, a rare subtype that mixes characteristics of Hodgkin and Non-Hodgkin forms of the disease. In one case from the University of Colorado Cancer Center using nivolumab (Opdivo?; Bristol-Myers Squibb Company) and two from the National Institutes of Health (NIH) using pembrolizumab, treatment with immune therapy checkpoint inhibitors followed unsuccessful therapies and was based on clinicians’ ability to match the mechanism of the drug with the known molecular alterations in this lymphoma.
These three cases represent the first successful uses of immune therapies in gray zone lymphoma, potentially paving the way for clinical trials utilizing this strategy in this and related conditions.
“For me, trying nivolumab was a binary choice: I could try the drug or I could give up,” noted Bobbie Flexer, PhD, the patient treated at CU Cancer Center. Flexer, a retired mathematics education professor from CU Boulder, had not improved after multiple rounds of chemotherapy and radiation therapy.
Genetic testing of Flexer’s tissue showed focal over-expression of the protein PD-L1. This protein displayed on a tumor cell’s surface acts as a white flag telling the immune system’s T cells not to attack. Specifically, T-cells probe other cells with their own cell-surface protein, PD-1, and it is the interaction between PD-1 and PD-L1 that can disarm the immune system against a marked cell. A major strategy of cancer immunotherapy is to block this interaction between a T cell’s PD-1 and a cancer cell’s PD-L1. If one is blinded from seeing the other, the immune system can be reactivated to attack cancer cells.
This is the strategy of nivolumab. It blocks PD-L1 from binding to PD-1 (it inhibits this checkpoint) thus removing the immune system’s blinders to cancer. The drug is approved as a first-line therapy for metastatic melanoma and has also been used to treat non-small cell lung cancer, Hodgkin disease and renal cancer. It had not previously been used against gray zone lymphoma.
“It was a leap of faith when we started the drug,” says Flexer’s oncologist, Manali Kamdar, MD, investigator at the CU Cancer Center and Clinical Director of Lymphoma Services at University of Colorado Hospital. Kamdar joined the Center in fall 2014 to establish the lymphoma program. She explains that there are about 100 different types of lymphoma, one of which is gray zone lymphoma.
“It’s so gray that no one knows how to spell it — should it be an ‘e’ or an ‘a’ in gray?” Kamdar says. “This is true to the point that not every pathologist will even call it gray zone lymphoma. This highlights the importance of academic medical centers. If you have a diagnosis of a rare subtype of lymphoma, it is pertinent to get a second opinion at an academic medical center to avoid misdiagnosis.”
Chemotherapy is only effective in roughly 50 percent of grey zone lymphoma, due in part to the aggressive nature of the condition and in part to the difficulty of obtaining a co