Daratumumab Produces Sustained Remission in a Patient With Refractory Extranodal NK Cell–T-Cell Lymphoma
In a letter to the editor in The New England Journal of Medicine, Hari et al described a sustained response to the anti-CD38 antibody daratumumab (Darzalex) in a patient with relapsed, refractory nasal-type extranodal natural killer (NK) cell–T-cell lymphoma.
In September 2014, a 56-year-old woman of Taiwanese descent was diagnosed with extranodal NK cell–T-cell lymphoma, with Ann Arbor stage IE. The tumor biopsy was positive for CD2, cytoplasmic CD3, CD56, and TIA-1 and negative for CD4, CD5, CD7, CD8, CD20, and CD30 on immunohistochemistry. Epstein-Barr virus–encoded RNA in situ hybridization and plasma polymerase chain reaction assay for Epstein-Barr virus DNA were positive.
At 6 weeks after radiotherapy and concurrent cisplatin followed by consolidation with cisplatin, etoposide, and ifosfamide, disease relapsed with extensive involvement of soft tissue, bone, brain, and spinal cord as well as spinal fluid. The patient then received pegylated asparaginase (Oncaspar)-based combination therapy consisting of dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide and intrathecal chemotherapy followed by allogeneic hematopoietic cell transplantation.
At 21 days after transplantation, the disease relapsed in the central nervous system, with aberrant NK cells found in the cerebrospinal fluid. Systemic relapse was found at day 90 via positive plasma polymerase chain reaction for Epstein-Barr virus DNA and aberrant NK cells in peripheral blood. Systemic remission was not achieved by halting immunosuppression and providing two additional cycles of gemcitabine, oxaliplatin, and pegylated asparaginase; cerebrospinal fluid became intermittently negative for NK cells.
Daratumumab Treatment
At 5 months after transplantation, persistence of disease was shown by plasma Epstein-Barr virus positivity and circulating aberrant CD38-positive NK cells. The patient was treated with off-label daratumumab at 16 mg/kg/wk as monotherapy.
During the first 4 weeks of treatment, plasma Epstein-Barr virus titers increased by a factor of 10 to > 20,000 copies/mL. After 6 weeks, Epstein-Barr virus became undetectable by polymerase chain reaction, and no evidence of residual disease was found on subsequent positron-emission tomography/computed tomography, plasma Epstein-Barr virus polymerase chain reaction, or blood and cerebrospinal fluid specimens. These findings persisted at 21 weeks of follow-up, marking the longest sustained remission since diagnosis.
The investigators stated: “We report a sustained response to an anti-CD38 antibody, daratumumab, in a patient with relapsed, refractory nasal-type extranodal NK cell–T-cell lymphoma…. We observed increasing [Epstein-Barr virus] titers in the first 5 weeks of treatment with daratumumab, followed by a sustained decrease in [Epstein-Barr virus] titers and an absence of detectable virus. Further studies of anti-CD38 antibodies in this highly aggressive cancer are needed.”
Parameswaran Hari, MD, of the Medical College of Wisconsin in Milwaukee, is the corresponding author of The New England Journal of Medicine letter.
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