Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study

Abstract

Background: Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL.

Methods: This phase 2 study with Simon's two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification).

Results: In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5-43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29-339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43-106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94-438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab.

Conclusions: In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.

Keywords: CD38; Daratumumab; NK/T-cell lymphoma.

Conflict of interest statement

TMK reports consulting for AstraZeneca, Novartis, Takeda, Sanofi, and Bayer, and research funding from AstraZeneca; DHY reports research funding from Janssen; HK, TZ, GG, and ZD are employees of Janssen; MQing and MQi are employees of Janssen and own equity in Janssen; WSK reports research funding from Roche, Kyowa Kirin, Novartis, Janssen, Mundipharma, Celltrion, and Donga; HH, JZ, MY, S-GC, HSE, STL, S-PY, YSong, YLK, JSK, JJ, and YShi have no conflicts to disclose.

Figures

Fig. 1

Swim lane plot for duration of response based on central review in daratumumab-treated responders. Responses are shown (PR). Five patients had progressive disease (PD) and 2 patients discontinued treatment based on investigator’s assessment of PD (*) and no further assessment of response occurred due to withdrawal from study. The arrow indicates ongoing treatment at clinical cutoff date (1 patient). PD, progressive disease; PR, partial response

Fig. 2

Summary of plasma EBV-DNA levels over time. Median plasma EBV-DNA loads (kIU/L) over time are shown for responders and nonresponders in the pharmacodynamic analysis population. Responses were based on central review. Nonevaluable patients were considered nonresponders. C, Cycle; D, Day; EBV, Epstein–Barr virus; EOT, end of treatment

Fig. 3

a Progression-free survival and b overall survival in patients with relapsed or refractory natural killer/T-cell lymphoma treated with daratumumab. Kaplan–Meier curves are shown for the overall population (all-treated patients; n = 32) and for responders (n = 8) and nonresponders (n = 24). Responses were based on central review. Nonevaluable patients were considered nonresponders