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Loncastuximab tesirine in relapsed or refractory DLBCL: Results from a phase II trial

Jun 17, 2021

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The CD19-targeted antibody–drug conjugate, loncastuximab tesirine, was recently added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for the treatment of B-cell lymphomas. The approval of loncastuximab tesirine by the U.S. Food and Drug Administration (FDA) was based on the results of the phase II LOTIS-2 trial (NCT03589469), as previously reported on the Lymphoma Hub. The drug can be used as a treatment option for patients with diffuse large B-cell lymphoma (DLBCL) who have relapsed following ≥2 lines of systemic therapy.

The phase II LOTIS-2 trial results have now been published in The Lancet Oncology by Caimi et al,1 and the Lymphoma Hub is pleased to provide a summary of the study.

Study design

A single-arm, multicenter trial in patients aged ≥18 years with relapsed/refractory (R/R) DLBCL who received ≥2 prior lines of systemic therapy and had an Eastern Cooperative Oncology Group (ECOG) performance status 0–2. Loncastuximab tesirine was given to eligible patients (N = 145) intravenously on Day 1 of each 21-day cycle (150 µg/kg for two cycles, followed by 75 µg/kg per cycle for up to 1 year).

  • The primary endpoint was overall response rate (ORR), defined according to 2014 Lugano classification as the proportion of patients with best overall response (complete response [CR] or partial response [PR]).
  • Secondary endpoints included duration of response, CR rate, relapse-free, progression-free, and overall survival, and the frequency and severity of adverse events (AEs). 


The primary analyses of anti-tumor activity and safety were based on all patients who received at least one dose of loncastuximab tesirine (as-treated population, N = 145). Of these, 137 (94%) discontinued treatment during follow-up, the most common reason for this being disease progression, which occurred in more than half of the patients (59%). The baseline characteristics are presented in Table 1.

Table 1. Baseline characteristics*


As-treated population (N = 145)

Male/female sex, %


Median age, years (IQR)

66 (56–71)

Histology, %














Disease stage at enrolment, %





Previous systemic therapies, %

2 lines


3 lines


>3 lines


Response to first-line systemic therapy, %







Response to most recent line systemic therapy, %







Refractory to all previous therapies, %







Relapse within 3 months of first-line therapy, %


Relapse within 6 months of first-line therapy, %


ABC, activated B-cell; DLBCL, diffuse large B-cell lymphoma; GCB, germinal center B-cell; HGBCL, high-grade B-cell lymphoma; HSCT, hematopoietic stem cell transplant; IQR, interquartile range; NE, not evaluable; PMBCL, primary mediastinal B-cell lymphoma.
*Data from Caimi et al.1
Investigator reported without independent testing.
Previous HSCT is included; for patients who received an autologous transplant, the mobilization regimen was considered a line of therapy if it was chemotherapy-based and distinct from the other previous lines of treatment.

Response and survival outcomes

  • ORR was 48% (95% CI, 39.9–56.7), and patients achieving a CR and PR were equivalent (Table 2).
  • The median time to first response (CR or PR) was 41 days (IQR, 38–44) and the median duration of response was 10.3 months (95% CI, 6.9–not estimable); 13.4 months for patients with CR and 5.7 months for patients with PR.
  • Of the responders, 64% maintained responses for ≥9 months.
  • Median progression-free, overall, and relapse-free survival were 4.9 months (95% CI, 2.9–8.3), 9.9 months (95% CI, 6.7–11.5), and 13.4 months (95% CI, 10.3–not estimable), respectively.
  • Sixty-eight of 145 patients received subsequent therapy; 15 received CD19-directed chimeric antigen receptor (CAR) T-cell therapy. The ORR and CR rates to CAR T-cell therapy for these 15 patients were 47% and 40%, respectively.
  • The median duration of treatment was 45 days (IQR, 22–113). The median average weight-adjusted dose per cycle was 113.5 µg/kg, and there was a median of 3 treatment cycles (IQR, 2–5).

Table 2. Response to loncastuximab tesirine in patients with R/R DLBCL assessed by central independent review*

Response, %

As-treated population (N = 145)

Overall response rate

48.3 (95% CI, 39.9–56.7)

Complete response rate

24.1 (95% CI, 17.4–31.9)

Complete response


Partial response


Stable disease


Progressive disease


Not evaluable


CI, confidence interval.
*Data from Caimi et al.1
Patients without PET-CT scan or whose scan was determined to be not evaluable by the independent reviewer.

Adverse events

  • Almost all patients (99%) reported at least one treatment-emergent AE (TEAE), the most common being neutropenia (26%), thrombocytopenia (18%), and increased gamma-glutamyl transferase (17%).
  • At least one serious TEAE was reported in 39% of patients, with 15% considered to be related to loncastuximab tesirine. The most common of these were febrile neutropenia (4%), pleural effusion (1%), non-cardiac chest pain (1%), and pericardial effusion (1%).
  • TEAEs related to pyrrolobenzodiazepine payload included edema or effusion (31%), skin or nail AEs (43%), and liver enzyme abnormalities (51%) and were mostly mild to moderate in severity and reversible.
  • Dose modification or treatment discontinuation due to TEAEs was required in 62% of patients. Dose delays were the most common modifications, seen in more than half of patients (51%).
  • More than half of patients died (53%); most deaths (78%) were due to disease progression. Fatal TEAEs were seen in only 6% of patients and these were not considered to be related to loncastuximab tesirine.


The study shows that loncastuximab tesirine produces durable responses in heavily pretreated patients with R/R DLBCL, including patients who had maintained CD19 expression after prior CD19-directed CAR T-cell therapy. Response to subsequent consolidation with HSCT or CAR T-cell therapy in some patients who had received loncastuximab tesirine highlights the potential for loncastuximab tesirine as a bridge to other therapies. A study evaluating loncastuximab tesirine plus ibrutinib (NCT03684694) is currently underway and has shown promising initial results.

  1. Caimi PF, Ai W, Alderuccio JB, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22:790-800. DOI: 1016/S1470-2045(21)00139-X

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