LOTIS-2 follow-up analysis: updated results from a phase 2 study of loncastuximab tesirine (Lonca) in relapsed or refractory diffuse large B-cell lymphoma
Kahl, B. S. Hamadani, M. Caimi, P. F. Carlo-Stella, C. Ai, W. Y. Alderuccio, J. P. Ardeshna, K. M. Hess, B. Radford, John A Solh, M.
Kahl, B. S.
Hamadani, M.
Caimi, P. F.
Carlo-Stella, C.
Ai, W. Y.
Alderuccio, J. P.
Ardeshna, K. M.
Hess, B.
Radford, John A
Solh, M.
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Abstract
Context: Patients with relapsed/refractory diffuse large B-cell
lymphoma (R/R DLBCL) who are ineligible for, or relapse after,
salvage chemotherapy/stem cell transplant (SCT) have a poor
prognosis. Lonca comprises a humanized anti-CD19 antibody
conjugated to a potent pyrrolobenzodiazepine dimer toxin.
Objective:To assess updated effi cacy and safety fi ndings from a Phase
2 study evaluating Lonca in patients with R/R DLBCL (LOTIS-2;
NCT03589469). Design: Multicenter, open-label, single-arm Phase
2 study in adult patients (≥18 years) with pathologically defined R/R
DLBCL and ≥2 prior systemic treatments. Intervention: Lonca
(150 µg/kg every 3 weeks [Q3W] for 2 cycles; 75 µg/kg Q3W
thereafter). Main Outcomes Measures: Primary effi cacy endpoint:
Overall response rate (ORR), assessed by central review. Secondary
effi cacy endpoints: Duration of response (DoR), progression-free
survival (PFS), and overall survival (OS). Safety analyses: Treatment-emergent adverse events (TEAEs). Follow-up period: Q12W for
up to 3 years after end of treatment. Results: 145 patients with R/R
DLBCL received ≥1 Lonca dose. Median age was 66 years (range
23–94). Patients received a median of 3 prior therapies (range 2–7).
At data cut-off (October 26, 2020, 12 months since first dose), 2 patients continued treatment. Patients received a mean of 4.6 Lonca
cycles (std 4.1; range 1–22). ORR was 48.3% (complete response
[CR]: 24.8%; partial response [PR]: 23.4%). Median DoR was 12.6
months for patients with CR or PR (n=70); not reached for patients
with CR. Median PFS and OS were 4.9 and 9.5 months, respectively.
Post-Lonca treatment, 15 patients received CD19-directed chimeric
antigen receptor T-cell therapy with an investigator-assessed ORR
of 46.7%, and 11 patients proceeded to SCT as consolidation
after Lonca response. Most common (≥25.0%) all-grade TEAEs
were increased gamma-glutamyltransferase (41.4%), neutropenia
(40.0%), thrombocytopenia (33.1%), fatigue (27.6%), and anemia
(26.2%). Grade 3 TEAEs occurred in 107 (73.8%) patients.
Treatment-related TEAEs leading to treatment discontinuation
and dose delays occurred in 26 (17.9%) and 62 (42.8%) patients,
respectively. Conclusions: After longer follow-up of patients in
LOTIS-2, durable responses to Lonca continue to be observed
in heavily pre-treated patients with R/R DLBCL. No new safety
concerns occurred. Research funding: ADC Therapeutics SA.
Keywords: non-Hodgkin lymphoma, diffuse large B-cell lymphoma,
antibody-drug conjugate, loncastuximab tesirine, Phase 2
Description
Date
2021
Publisher
Collections
Keywords
Type
Other
Citation
Kahl BS, Hamadani M, Caimi PF, Carlo-Stella C, Ai WY, Alderuccio JP, et al. LOTIS-2 Follow-Up Analysis: Updated Results from a Phase 2 Study of Loncastuximab Tesirine (Lonca) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Clinical Lymphoma Myeloma & Leukemia. 2021;21:S377-S8.