Recently, ADCs have expanded the DLBCL therapeutic landscape, with the approvals of CD79b-targeted polatuzumab vedotin and CD19-directed loncastuximab tesirine for R/R and even frontline disease. However, the clinical application of ADCs is accompanied by challenges, including the management of characteristic toxicities, understanding and overcoming mechanisms of resistance. This review systematically synthesizes the mechanisms of action, updated clinical evidence, toxicity profiles, and resistance mechanisms of ADCs in DLBCL, while also discusses management strategies and provides perspectives on future directions.

2 months ago

Review • Journal

TNFRSF8 (TNF Receptor Superfamily Member 8) • CD79B (CD79b Molecule) • CD22 (CD22 Molecule)

Rituxan (rituximab) • Zynlonta (loncastuximab tesirine-lpyl) • Polivy (polatuzumab vedotin-piiq)

3ms

A Phase II Study of Loncastuximab Tesirine as Consolidation Strategy in Patients With LBCL in PR After CAR T-cell Therapy (clinicaltrials.gov)

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2030 | Trial primary completion date: Jan 2026 --> Jan 2030

3 months ago

Trial completion date • Trial primary completion date

Zynlonta (loncastuximab tesirine-lpyl)

4ms

EPCOR+LONCA: Epcoritamab in Combination With Loncastuximab Tesirine in Relapsed/Refractory Large B-cell Lymphoma (clinicaltrials.gov)

P2, N=26, Recruiting, University of Miami | Not yet recruiting --> Recruiting

4 months ago

Enrollment open

Epkinly (epcoritamab-bysp) • Zynlonta (loncastuximab tesirine-lpyl)

5ms

LOTIS 5: Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov)

P3, N=440, Active, not recruiting, ADC Therapeutics S.A. | Trial primary completion date: Jun 2025 --> Jan 2026

5 months ago

Trial primary completion date

BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)

gemcitabine • Rituxan (rituximab) • oxaliplatin • Zynlonta (loncastuximab tesirine-lpyl)

6ms

Loncastuximab Tesirine in Combination With DA-EPOCH-R in Patients With Previously Untreated Aggressive B-cell Lymphoid Malignancies (clinicaltrials.gov)

P1, N=11, Active, not recruiting, Medical College of Wisconsin | N=33 --> 11 | Trial completion date: May 2026 --> Oct 2027 | Trial primary completion date: May 2026 --> May 2025 | Recruiting --> Active, not recruiting

6 months ago

Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date

BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)

Rituxan (rituximab) • cyclophosphamide • etoposide IV • pegylated liposomal doxorubicin • vincristine • prednisone • Zynlonta (loncastuximab tesirine-lpyl) • Marqibo (vincristine liposomal)

6ms

Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov)

P2, N=36, Recruiting, City of Hope Medical Center | Trial completion date: Aug 2025 --> Apr 2026 | Trial primary completion date: Aug 2025 --> Apr 2026

6 months ago

Trial completion date • Trial primary completion date

CD20 (Membrane Spanning 4-Domains A1)

CD20 positive

Zynlonta (loncastuximab tesirine-lpyl) • Lunsumio (mosunetuzumab-axgb)