Pembrolizumab Induces Remission in Small Cohort of Patients With Natural Killer/T-Cell Lymphomas

For the 20 to 40 percent of patients with natural killer (NK)/T-cell lymphomas who do not respond to regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, etoposide) that also contain L-asparaginase, outcomes remain poor. Because NK/T-cell lymphomas are infected by Epstein-Barr virus (EBV) and these cells upregulate programmed death ligand 1 (PDL1), targeting the PDL1 axis could be a potential treatment option for patients with these lymphomas.

In a study published in Blood, Yok-Lam Kwong, MD, from the Department of Medicine at Queen Mary Hospital in Hong Kong, and co-authors retrospectively analyzed the use of pembrolizumab in a cohort of seven men (median age = 49 years; range = 31-68 years) with relapsed/refractory NK/T-cell lymphomas who had not responded to L-asparaginase regimens.

The study included patients from Hong Kong, Singapore, and Seoul. They received pembrolizumab 2 mg/kg every three weeks (1 patient received it every 2 weeks). Most patients had advanced-stage disease with widespread organ involvement. Five patients had systemic hemophagocytic syndrome (HPS) prior to pembrolizumab treatment, and two patients had relapsed after allogeneic hematopoietic cell transplantation (alloHCT). The median number of prior therapies (including alloHCT) was two (range = 1-5 therapies), and no patient had responded to SMILE or SMILE-like regimens.

After a median of seven cycles (range = 2-13 cycles) and a median follow-up of six months (range = 2-10 months), five patients remained in complete response (CR) and two patients achieved a partial response (PR).

Three patients achieved clinical and radiologic CR, including two cases of molecular remission (undetectable EBV DNA) but with minimal EBV-encoded-RNA-positive cells in lesions comprising predominantly CD3+CD4+ and CD3+CD8+ T cells, “which ultimately disappeared, suggesting pseudo-progression,” the authors wrote.

“Responses after pembrolizumab treatment require clinical, radiologic, pathologic, and molecular assessment,” the authors wrote, and these responses were often “discordant.”

The authors outlined two cases in which patients had advanced disease and responded to pembrolizumab treatment. One patient had biopsy-proven esophageal involvement and radiologic pulmonary infiltration, and Dr. Kwong and co-authors reported that “pembrolizumab treatment led to immediate improvement, and a positron emission tomography/computed tomography (PET/CT) scan after six cycles showed metabolic CR.” The patient then continued to receive six more cycles of pembrolizumab.

Another patient who presented with marrow involvement, cytopenia, and HPS relapsed following alloHCT. Following two cycles of pembrolizumab, laboratory monitoring found that EBV DNA levels fell to undetectable levels; after three cycles, marrow examination and PET/CT imaging confirmed CR.

“However, in the presence of continued clinical remission, detectable EBV DNA was not necessarily associated with disease progression,” the authors wrote. In one patient, HPS resolved and EBV DNA fell to undetectable levels after the first cycle of pembrolizumab, but new lesions unexpectedly appeared in his abdominal wall and other areas after subsequent cycles. “This is different from chemotherapy treatment,” Dr. Kwong wrote, “in which persistently positive EBV DNA portends a poor prognosis.”

Four patients had uniformly strong PDL1 expression, whereas another patient had weaker staining in about 20 percent of cells; the remaining two patients did not have data available. “Strong PDL1 expression correlated with excellent responses,” the authors concluded.

One patient who underwent alloHCT developed grade 2 rash, but no other adverse events were reported. The study is limited by its retrospective design, small patient population, and short duration of follow-up.


Kwong YL, Chan TSY, Tan D, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase. Blood. 2017 February 10. [Epub ahead of print]