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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.
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 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*
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. |
|
Characteristic |
As-treated population (N = 145) |
---|---|
Male/female sex, % |
59/41 |
Median age, years (IQR) |
66 (56–71) |
Histology, % |
|
DLBCL, NOS |
88 |
HGBCL |
8 |
PMBCL |
5 |
GCB or ABC DLBCL,† % |
|
GCB |
33 |
ABC |
16 |
Unknown |
51 |
Disease stage at enrolment, % |
|
I-II |
23 |
III-IV |
77 |
Previous systemic therapies,‡ % |
|
2 lines |
43 |
3 lines |
24 |
>3 lines |
32 |
Response to first-line systemic therapy, % |
|
Relapse |
68 |
Refractory |
20 |
Unknown/NE/missing |
12 |
Response to most recent line systemic therapy, % |
|
Relapse |
30 |
Refractory |
58 |
Unknown/NE/missing |
12 |
Refractory to all previous therapies, % |
|
Yes |
17 |
No |
79 |
Unknown/NE/missing |
3 |
Relapse within 3 months of first-line therapy, % |
24 |
Relapse within 6 months of first-line therapy, % |
39 |
Table 2. Response to loncastuximab tesirine in patients with R/R DLBCL assessed by central independent review*
Response, % |
As-treated population (N = 145) |
---|---|
CI, confidence interval. |
|
Overall response rate |
48.3 (95% CI, 39.9–56.7) |
Complete response rate |
24.1 (95% CI, 17.4–31.9) |
Complete response |
24 |
Partial response |
24 |
Stable disease |
15 |
Progressive disease |
21 |
Not evaluable† |
16 |
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.
References
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