Loncastuximab tesirine
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-LONCASTUXIMAB-TESIRINE |
|---|---|
| Type | Drug |
| Aliases | ADCT-402Zynlontaloncaloncastuximab tesirine-lpylЛонкастуксимаб тезирин |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | DIS-DLBCL-NOS |
| Sources | SRC-ESMO-DLBCL-2024 SRC-LOTIS-2-CAIMI-2021 SRC-NCCN-BCELL-2025 |
Drug Facts
| Class | Anti-CD19 antibody-drug conjugate (ADC) with pyrrolobenzodiazepine (PBD) dimer payload |
|---|---|
| Mechanism | Humanized IgG1κ monoclonal antibody targeting CD19, conjugated via a cathepsin-cleavable valine-alanine linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer warhead. Average drug-to-antibody ratio ~2.3. After binding surface CD19 on B-cell lymphoma cells, the ADC is internalized; cathepsin B cleavage in the lysosome releases the PBD payload, which alkylates and cross-links DNA in the minor groove without distorting the helix — these cross-links evade DNA repair and trigger apoptosis. PBD warheads retain activity in cells resistant to topoisomerase or microtubule-targeting payloads. FDA-approved April 2021 for relapsed/refractory diffuse large B-cell lymphoma (DLBCL NOS, DLBCL arising from low-grade lymphoma, high-grade B-cell lymphoma) after ≥2 prior systemic lines (LOTIS-2). EMA approval December 2022. |
| Typical dosing | 150 µg/kg IV every 3 weeks for cycles 1-2, then 75 µg/kg IV every 3 weeks from cycle 3 onward, until disease progression or unacceptable toxicity. Premedication with dexamethasone 4 mg PO BID × 3 days (starting day prior to infusion, day of, and day after) is mandatory to reduce edema, effusions, and infusion reactions. Dose adjustments: hold for ANC <1.0 × 10⁹/L, platelets <50 × 10⁹/L, GGT >2.5× ULN, or effusions / edema requiring intervention; reduce by 25-50% on resumption if recurrent. No dose adjustment for renal impairment (CrCl ≥30 mL/min) or mild hepatic impairment; not studied in severe hepatic impairment (avoid). Median 3-5 cycles in LOTIS-2. |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-04-27 |
Notes
Pivotal: LOTIS-2 (Caimi et al., Lancet Oncol 2021) — 145 R/R DLBCL patients with ≥2 prior lines (~99% prior R-CHOP, ~17% prior CAR-T), ORR 48%, CR 24%, median DoR 13.4 months in responders. Single-agent activity in heavily pretreated population including post-CAR-T failures. Position in DLBCL algorithm: 3L+ option after R-CHOP and CAR-T (or in CAR-T-ineligible patients), competing with polatuzumab vedotin + bendamustine + rituximab (Pola-BR) and bispecific antibodies (epcoritamab, glofitamab). Edema/effusion management is the principal toxicity issue: mandatory dexamethasone premedication, monitor weight + auscultation each cycle, drain effusions when symptomatic. Skin photosensitivity requires SPF50+ broad-spectrum sunscreen and protective clothing throughout treatment + 1 month after. Ukraine: NOT registered, NOT NSZU-reimbursed; access via self-pay (~USD 30-40K per 6-cycle course) or compassionate-use program through ADC Therapeutics / Sobi. LOTIS-5 (lonca + R-GemOx) ongoing for 2L use.
Used By
Regimens
REG-LONCASTUXIMAB-TESIRINE- Loncastuximab tesirine monotherapy (R/R DLBCL, 3L+; LOTIS-2)