Case Report Suggests Nivolumab Is Effective in Burkitt Lymphoma

A new case report is raising the possibility that nivolumab (Opdivo) may be able to successfully treat an aggressive form of non-Hodgkin lymphoma.

Burkitt lymphoma affects about 1200 people each year in the United States. While high-dose chemotherapy improves outcomes, corresponding author B. Scott Colton, MD, and colleagues at the University of California, Los Angeles, wrote that successfully treating patients with refractory disease is “formidable clinical challenge,” particularly when the disease is rapidly progressing.

Such was the case for a 72-year-old man who appeared at the hospital with abdominal comfort, was sent home after lab tests showed nothing notable, and then returned 4 days later, at which point he was diagnosed with Burkitt lymphoma.

The patient’s tumor cells were negative for Epstein-Barr virus and programmed cell death ligand 1 (PD-L1), though the investigators noted a very small number of macrophages and lymphocytes within the tumor were positive for PD-L1. Physicians diagnosed tumor lysis syndrome and began hemodialysis. The patient was given a dose of corticosteroid.

A lumbar puncture was negative for cancer cells, and the patient was given intrathecal methotrexate.

Next, physicians began administering the Magrath chemotherapy regimen, which calls for rituximab, cyclophosphamide, doxorubicin, vincristine, and methotrexate on cycles 1 and 3, and rituximab, ifosfamide, etoposide, and high-dose cytarabine on cycles 2 and 4.

After the first cycle, the patient had a marked reduction in tumor burden and reductions in lactate dehydrogenase (LDH) levels, a peripheral marker of cancer. However, LDH levels reversed course a few days before his second cycle of chemotherapy. That cycle caused his LDH levels to return to normal levels, but then they began to increase again, a sign that the disease was rapidly progressing.

At that point, the patient’s options were becoming very limited. The clinicians discussed the possibility of hospice care, but they also proposed another solution: nivolumab. The PD-L1 inhibitor has been used to treat other types of lymphoma, and Colton said there were promising reasons to suggest it might work here.

Colton noted that since the development of therapies like nivolumab, the drugs have shown promise in a number of different types of malignancies.

“One pattern that arose was that tumors that had increased antigen production and those associated with concurrent viral infections may have better responses to immunotherapy options,” he said. As a result, drugs like nivolumab began to be used successfully for types of lymphoma, though he said the reasons for the drug’s success in these cases is not yet fully understood.

“Given these patterns, our current knowledge of Burkitt’s lymphoma, and known examples where single agent nivolumab had shown to be effective in other types of lymphoma, we felt it was a viable option to attempt in this patient who had recently proven to have disease refractory to the standard-of-care chemotherapy treatment,” Colton told The American Journal of Managed Care® (AJMC®).

Colton said the patient was made aware of the possible side effects and the fact that it was not a proven treatment, but the patient liked the fact that checkpoint inhibitors are usually well-tolerated and was pleased that it would not require additional chemotherapy. The patient was put on a dose of 480 mg of nivolumab every 4 weeks. Doctors later added rituximab and lenalidomide to enhance disease control, but discontinued the latter after it resulted in severe fatigue.

Nivolumab decreased the patient’s LDH levels to normal range, and at the time of the case report’s writing, the patient’s levels remained in normal range for 5 months.

The patient had no symptoms and scans showed no evidence of disease 4 months after nivolumab treatment.

Colton told AJMC that it has now been 8 months without evidence of disease, so he and colleagues are cautiously optimistic about the patient’s prognosis. However, he added that the patient would face a very poor prognosis if he were to have a recurrence.

Still, he said the “exciting tail on the Kaplan Meier curves” that initially caused him and colleagues to propose nivolumab suggests the possibility of a sustained response or even cure.

“The longer out the patient gets from initiation of therapy, the better the chances his disease will not come back,” he said.