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Three case reports published in The New England Journal of Medicine describe the successful use of PD-1 inhibitors in gray zone lymphoma.
Two patients who had failed treatment with DA-EPOCH-R (dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab) ultimately responded to treatment with pembrolizumab.
Another patient—who had previously received 2 chemotherapy regimens, monotherapy with brentuximab vedotin, and radiation—responded to treatment with nivolumab.
Pembrolizumab treatment
An 18-year-old woman with mediastinal gray-zone lymphoma initially had a partial response to DA-EPOCH-R. However, she progressed 6 weeks after salvage radiotherapy.
She went on to receive pembrolizumab, had a complete metabolic response, and proceeded to allogeneic transplant after 235 days of treatment.
A 76-year-old man with mediastinal gray-zone lymphoma also had a partial response to DA-EPOCH-R but later progressed.
He proceeded to pembrolizumab and had a complete metabolic response. He was still in remission on day 381 of treatment.
Nivolumab treatment
The patient who received nivolumab is Bobbie Flexer, an 80-year-old retired mathematics professor.
“For me, trying nivolumab was a binary choice: I could try the drug or I could give up,” Flexer said.
She had initially achieved a complete metabolic response to DA-EPOCH-R, but her disease progressed after 6 cycles of treatment.
“Given Bobbie’s age and her resistance to chemotherapy, it was difficult to simply increase her dose,” said Flexer’s oncologist, Manali Kamdar, MD, of the University of Colorado School of Medicine in Aurora.
“Bobbie’s tumor biopsy expressed a protein called CD30, and so we started her on brentuximab, which targets these CD30 cells. Unfortunately, Bobbie’s disease progressed through multiple cycles of brentuximab. Subsequently, we switched her to another combined chemotherapy—namely, gemcitabine with oxaliplatin [plus rituximab].”
When that regimen and mediastinal radiation both proved unsuccessful, Dr Kamdar started Flexer on nivolumab.
“Within one dose, she was in less pain, and she looked much better,” Dr Kamdar said.
A PET scan after 6 doses showed that Flexer’s disease was in complete remission, and she was still in remission on day 161 of treatment.
She did experience adverse effects, including 2 bouts of pneumonitis, which were successfully treated with prednisone.
Flexer also experienced an uptick in pancreas enzymes that caused high blood glucose levels. She is learning to treat that side effect with insulin. And dietitians helped her manage expected gut-related side effects of nivolumab.
To Dr Kamdar, Flexer’s case was striking enough to warrant submitting a report to NEJM.
Coincidentally, the journal had just received 2 similar case reports from the National Institutes of Health, in which researchers had used pembrolizumab to target gray zone lymphoma in a nearly identical way.
Together, these cases suggest a new strategy for treating gray zone lymphoma. 
Three case reports published in The New England Journal of Medicine describe the successful use of PD-1 inhibitors in gray zone lymphoma.
Two patients who had failed treatment with DA-EPOCH-R (dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab) ultimately responded to treatment with pembrolizumab.
Another patient—who had previously received 2 chemotherapy regimens, monotherapy with brentuximab vedotin, and radiation—responded to treatment with nivolumab.
Pembrolizumab treatment
An 18-year-old woman with mediastinal gray-zone lymphoma initially had a partial response to DA-EPOCH-R. However, she progressed 6 weeks after salvage radiotherapy.
She went on to receive pembrolizumab, had a complete metabolic response, and proceeded to allogeneic transplant after 235 days of treatment.
A 76-year-old man with mediastinal gray-zone lymphoma also had a partial response to DA-EPOCH-R but later progressed.
He proceeded to pembrolizumab and had a complete metabolic response. He was still in remission on day 381 of treatment.
Nivolumab treatment
The patient who received nivolumab is Bobbie Flexer, an 80-year-old retired mathematics professor.
“For me, trying nivolumab was a binary choice: I could try the drug or I could give up,” Flexer said.
She had initially achieved a complete metabolic response to DA-EPOCH-R, but her disease progressed after 6 cycles of treatment.
“Given Bobbie’s age and her resistance to chemotherapy, it was difficult to simply increase her dose,” said Flexer’s oncologist, Manali Kamdar, MD, of the University of Colorado School of Medicine in Aurora.
“Bobbie’s tumor biopsy expressed a protein called CD30, and so we started her on brentuximab, which targets these CD30 cells. Unfortunately, Bobbie’s disease progressed through multiple cycles of brentuximab. Subsequently, we switched her to another combined chemotherapy—namely, gemcitabine with oxaliplatin [plus rituximab].”
When that regimen and mediastinal radiation both proved unsuccessful, Dr Kamdar started Flexer on nivolumab.
“Within one dose, she was in less pain, and she looked much better,” Dr Kamdar said.
A PET scan after 6 doses showed that Flexer’s disease was in complete remission, and she was still in remission on day 161 of treatment.
She did experience adverse effects, including 2 bouts of pneumonitis, which were successfully treated with prednisone.
Flexer also experienced an uptick in pancreas enzymes that caused high blood glucose levels. She is learning to treat that side effect with insulin. And dietitians helped her manage expected gut-related side effects of nivolumab.
To Dr Kamdar, Flexer’s case was striking enough to warrant submitting a report to NEJM.
Coincidentally, the journal had just received 2 similar case reports from the National Institutes of Health, in which researchers had used pembrolizumab to target gray zone lymphoma in a nearly identical way.
Together, these cases suggest a new strategy for treating gray zone lymphoma.
Three case reports published in The New England Journal of Medicine describe the successful use of PD-1 inhibitors in gray zone lymphoma.
Two patients who had failed treatment with DA-EPOCH-R (dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab) ultimately responded to treatment with pembrolizumab.
Another patient—who had previously received 2 chemotherapy regimens, monotherapy with brentuximab vedotin, and radiation—responded to treatment with nivolumab.
Pembrolizumab treatment
An 18-year-old woman with mediastinal gray-zone lymphoma initially had a partial response to DA-EPOCH-R. However, she progressed 6 weeks after salvage radiotherapy.
She went on to receive pembrolizumab, had a complete metabolic response, and proceeded to allogeneic transplant after 235 days of treatment.
A 76-year-old man with mediastinal gray-zone lymphoma also had a partial response to DA-EPOCH-R but later progressed.
He proceeded to pembrolizumab and had a complete metabolic response. He was still in remission on day 381 of treatment.
Nivolumab treatment
The patient who received nivolumab is Bobbie Flexer, an 80-year-old retired mathematics professor.
“For me, trying nivolumab was a binary choice: I could try the drug or I could give up,” Flexer said.
She had initially achieved a complete metabolic response to DA-EPOCH-R, but her disease progressed after 6 cycles of treatment.
“Given Bobbie’s age and her resistance to chemotherapy, it was difficult to simply increase her dose,” said Flexer’s oncologist, Manali Kamdar, MD, of the University of Colorado School of Medicine in Aurora.
“Bobbie’s tumor biopsy expressed a protein called CD30, and so we started her on brentuximab, which targets these CD30 cells. Unfortunately, Bobbie’s disease progressed through multiple cycles of brentuximab. Subsequently, we switched her to another combined chemotherapy—namely, gemcitabine with oxaliplatin [plus rituximab].”
When that regimen and mediastinal radiation both proved unsuccessful, Dr Kamdar started Flexer on nivolumab.
“Within one dose, she was in less pain, and she looked much better,” Dr Kamdar said.
A PET scan after 6 doses showed that Flexer’s disease was in complete remission, and she was still in remission on day 161 of treatment.
She did experience adverse effects, including 2 bouts of pneumonitis, which were successfully treated with prednisone.
Flexer also experienced an uptick in pancreas enzymes that caused high blood glucose levels. She is learning to treat that side effect with insulin. And dietitians helped her manage expected gut-related side effects of nivolumab.
To Dr Kamdar, Flexer’s case was striking enough to warrant submitting a report to NEJM.
Coincidentally, the journal had just received 2 similar case reports from the National Institutes of Health, in which researchers had used pembrolizumab to target gray zone lymphoma in a nearly identical way.
Together, these cases suggest a new strategy for treating gray zone lymphoma.