Daratumumab Monotherapy for Patients with Relapsed or Refractory (R/R) Natural Killer/T-Cell Lymphoma (NKTCL), Nasal Type: Updated Results from an Open-Label, Single-Arm, Multicenter Phase 2 Study

Hui-qiang Huang and Won-Seog Kim contributed equally to this work. Introduction: NKTCLs are rare, Epstein-Barr virus-associated distinct subtypes of peripheral T-cell lymphoma. These are primarily extranodal and of the nasal type and are more common in Asia and Central/South America (Tse and Kwong. Blood 2013. 121:4997-5005). Outcomes for patients (pts) with R/R NKTCL are very poor, and with no standard therapy, there exists a highly unmet medical need for this pt population. Clinical data from NKTCL pts suggest CD38 as a new prognostic biomarker and novel target for therapy (Wang et al. Ann Hematol 2015. 94:1381-8). Daratumumab (DARA) is a human IgGk monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action that is approved for newly diagnosed and relapsed/refractory multiple myeloma (MM). Interim results from stage 1 of a phase 2 study (NCT02927925) of DARA monotherapy in pts with R/R NKTCL demonstrated high tolerability and pre-specified futility criteria were not met (Kim et al. Blood 2018. 132:1617). Here we present data from stage 2 of the study. Methods: This phase 2 study with Simon's 2-stage design evaluated DARA monotherapy in pts with histologically confirmed extranodal NKTCL nasal type per WHO classification that was refractory to or relapsed after ≥1 line of chemotherapy, and who were not candidates for other treatment modalities. Pts without available tumor samples for biomarker determination were not eligible. DARA 16 mg/kg was administered by IV infusion once weekly for 8 weeks, every other week for 16 weeks, and every 4 weeks thereafter until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) based on blinded independent central review (BICR) per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification). Additional endpoints included progression-free survival (PFS) and duration of response based on BICR, overall survival (OS), and safety. Protocol-specified futility criterion for ORR (defined as at most 1 of 15 pts with complete response [CR]/partial response [PR]) was not met at interim analysis of 16 pts; stage 2 enrolled an additional 16 pts. Results: A total of 32 pts were treated with DARA monotherapy. Median age was 56 years, 91% had an ECOG score of 0 or 1, median time from initial NKTCL diagnosis was 24.0 months, median (range) plasma EBV-DNA at baseline was 900 (0-94,800) kIU/L, and 50% of pts had CD38 expr