Zynlonta (loncastuximab tesirine-lpyl) / Overland ADCT BioPharma, Tanabe Pharma, SOBI - LARVOL DELTA

Sequencing CD19-targeted therapies in patients with relapsed/refractory large B-cell lymphoma: A narrative review. (PubMed, Blood Rev) - "This review highlights recent trial and real-world data focusing on the efficacy and safety of the CD19-targeted agents tafasitamab-lenalidomide and loncastuximab tesirine before and after CAR-T therapy in patients with R/R B-cell lymphoma and addresses the importance of assessing pretreatment target antigen levels as well as identifying common molecular mechanisms of treatment failure. Additionally, this analysis discusses the unmet needs in patients with high-risk disease and the challenges of sequencing these therapeutic strategies, while providing expert clinical practice recommendations to optimize patient outcomes."

Journal • Review • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

A Study of JNJ-95566692 in Participants With Non-Hodgkin Lymphoid Malignancies (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=130 ➔ 340 | Trial completion date: Aug 2028 ➔ Oct 2029

Enrollment change • First-in-human • Trial completion date • B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • BCL2 • IRF4

Loncastuximab Tesirine in Combination with Venetoclax Is Safe and Shows Efficacy in Patients with Relapsed/Refractory Non Hodgkin Lymphoma (ASH 2024) - "Enrollment continues in a dose expansion cohort that also includes patients with r/r mantle cell lymphoma. Updated analyses with longer follow-up and expanded enrollment will be presented."

Clinical • Combination therapy • Acute Kidney Injury • Anemia • Atrial Fibrillation • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Leukopenia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • Thrombocytopenia • Waldenstrom Macroglobulinemia

Comparative Real-World Outcomes of Chimeric Antigen Receptor T-Cell Therapy vs Standard Systemic Therapy in Diffuse Large B-Cell Lymphoma (SOHO 2026) - "Patients: Adults (≥18 years) with DLBCL receiving CAR-T therapy were compared with those receiving non–CAR-T systemic therapies, including polatuzumab vedotin, tafasitamab, lenalidomide, bendamustine, platinum- or gemcitabine-based regimens, selinexor, or loncastuximab tesirine. In this large real-world propensity-matched cohort, CAR-T therapy was associated with higher long-term mortality and increased healthcare utilization compared with standard therapy. These findings likely reflect differences in patient selection, disease burden, and treatment-related toxicity. Increased ICU utilization and infections highlight the need for improved risk stratification and optimized supportive care in patients undergoing CAR-T therapy."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Comparative Efficacy and Safety of Approved Therapies in ≥3L Relapsed/Refractory Large B-Cell Lymphoma: A Bayesian Network Meta-Analysis (SOHO 2026) - "Background: Multiple novel agents are approved for ≥3L relapsed/refractory large B-cell lymphoma, including chimeric antigen receptor T-cell (CAR-T) products (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisacel]), bispecific antibodies (epcoritamab, glofitamab, mosunetuzumab), antibody-drug conjugates (polatuzumab vedotin + bendamustine, rituximab [pola-BR], loncastuximab tesirine), and others (tafasitamab + lenalidomide, selinexor). CAR-T therapies ranked highest for CR rate but with greater toxicity and selection bias. Among bispecific antibodies, epcoritamab ranked among the most favorable for combined efficacy and safety (SUCRA, 58.3% vs 56.1% for glofitamab and 47.8% for mosunetuzumab). Given the near-disconnected, star-topology network and predominantly single-arm data, results carry very low certainty per CINeMA and should be interpreted cautiously."

Retrospective data • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

THE PHS W-INDEX: A NOVEL PROGNOSTIC FRAMEWORK INTEGRATING NUTRITIONAL AND HEMATOLOGICAL MARKERS TO PREDICT OUTCOMES IN DLBCL PATIENTS TREATED WITH GLOFITAMAB (EHA 2026) - P=N/A | "89 (88.1%) had monotherapy, 12 (11.9%) systemic combinations, mostly R-GemOx (n=7), then Loncastuximab (n=2), Pola-BR, R-ICE, and Gemcitabine (all n=1). By integrating host fitness (nutrition, anemia, lymphopenia) with tumor burden, it enables improved risk stratification and early identification of high-risk patients for tailored management. Acknowledgement: Supported by the Ministry of Health of the Czech Republic (NU21-03-00411) DRO (FNOL, 00098892)."

Biomarker • Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Loncastuximab Tesirine with Rituximab Induces Robust and Durable Complete Metabolic Responses in High-Risk Relapsed/Refractory Follicular Lymphoma (ASH 2024) - P2 | "R-CHOP was the most common first-line therapy (56.5%), followed by bendamustine with rituximab (25.6%), single-agent rituximab (15.3%), and fludarabine, mitoxantrone and dexamethasone (2.6%). Conclusion : Loncastuximab with rituximab demonstrates dramatic activity with robust CMR and 12-month PFS of 94.2% in high-risk r/r FL. Our study supports this combination as a new treatment option in FL, and a multicenter expansion cohort is ongoing."

Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Fatigue • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mood Disorders • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Limited Duration Loncastuximab Tesirine with Rituximab Induces High Complete Metabolic Response Rate in High-Risk Relapsed/Refractory Follicular Lymphoma – a Phase 2 Study (ASH 2023) - P2 | "Premedication with dexamethasone 4 mg twice daily for 3 days was required with loncastuximab...R-CHOP was most common first-line therapy (n=14; 54%) followed by bendamustine with rituximab and single-agent rituximab (n=6; 23%; each)... A limited duration program combining loncastuximab with rituximab in patients with rel/ref FL is well tolerated and highly effective with a metabolic CR rate of 86% including high-risk patients with POD24 and/or high disease burden."

P2 data • B Cell Lymphoma • Biliary Cancer • Cholangiocarcinoma • Dermatology • Diffuse Large B Cell Lymphoma • Fatigue • Follicular Lymphoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Solid Tumor • Thrombocytopenia

Loncastuximab tesirine in heavily pretreated patients with large B-cell lymphoma: a German Lymphoma Alliance analysis. (PubMed, Blood Adv) - "Lonca demonstrated a favorable safety profile with moderate efficacy in heavily pretreated patients. While enabling timely access to subsequent therapy, efficacy in earlier lines with combination partners may further increase response rates and durability of response."

Journal • B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

A Phase 2, Open-Label Study of Loncastuximab Tesirine in Combination With Rituximab (Lonca-R) in Previously Untreated Unfi t/Frail Patients With Diffuse Large B-Cell Lymphoma (LOTIS-9) (SOHO 2022) - P2 | "Background: Rituximab in combination with chemotherapy (R [rituximab]-CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) is standard fi rst-line therapy for patients with diffuse large B-cell lymphoma (DLBCL). The study opened for recruitment in April 2022. This abstract was accepted for publication only at the 2022 EHA Congress. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group."

Clinical • Combination therapy • P2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab tesirine in relapsed/refractory high-grade B-cell lymphoma: a subgroup analysis from the LOTIS-2 study. (PubMed, Blood Adv) - No abstract available

Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Metabolic Tumor Volume Predicts Outcomes in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated with Loncastuximab Tesirine in the Lotis-2 Trial (ASH 2022) - P2 | "In the present analysis we demonstrated the predictive impact of PET/CT data in rel/ref DLBCL retaining its risk-stratification power as continuous and categorical variables. MTV is an imaging biomarker extracted from routine PET/CT scans and enables individualized treatment selection identifying those patients that will benefit the most from loncastuximab tesirine."

Biomarker • Clinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase II Trial of Loncastuximab Tesirine in Patients with Previously Treated Waldenström Macroglobulinemia (ASH 2024) - "This prospective phase II clinical trial was designed to evaluate the use of loncastuximab tesirine, a CD19 antibody drug conjugate, in patients with WM previously treated with at least two lines of therapy, including rituximab and a BTK inhibitor. This treatment has a manageable side effect profile with skin toxicity, asymptomatic GGT elevation, and transient cytopenias that have not led to treatment discontinuation. Accrual will continue to enroll 36 total patients."

Clinical • IO biomarker • P2 data • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CXCR4 • MYD88 • TP53

Limited Duration Loncastuximab Tesirine Induces a High Rate of Complete Responses in Patients with Relapsed/Refractory Marginal Zone Lymphoma - Report of First Planned Interim Futility Analysis of a Multicenter Phase II Study (ASH 2024) - P2 | "Premedication with dexamethasone 4 mg twice daily for 3 days and prophylaxis with spironolactone 100 mg (to prevent fluid overload) was required...At the time of study design, the best reported CR rate in r/r MZL was 16% achieved with umbralisib, that we used as P0 assumption under the null hypothesis...Across all lines of treatment, the most common treatments were R-chemotherapy (n=18), targeted/immuno-modulatory agents (n=7) and single-agent rituximab (n=7); 1 patient had CAR-T...The patient clinically fully recovered with normalization in LFTs abnormalities. Conclusion : Lonca is demonstrating clinically meaningful activity with robust CR rate in r/r MZL patients in our ongoing phase 2 study."

Clinical • IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: a single-centre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "Loncastuximab tesirine with rituximab showed clinically meaningful activity in relapsed or refractory follicular lymphoma, and had a manageable safety profile."

Journal • P2 data • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology

Deep Learning-Based Body Composition Analysis for Outcome Prediction in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Insights From the LOTIS-2 Trial. (PubMed, JCO Clin Cancer Inform) - P2 | "The pretreatment SM*/VF* body composition index shows promise as a biomarker for patients with rel/ref DLBCL undergoing treatment with loncastuximab tesirine. The proposed deep learning-based approach for body composition analysis demonstrated comparable performance to the manual process, presenting a more cost-effective alternative to conventional methods."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Initial Results From LOTIS-7: A Phase 1b Study of Loncastuximab Tesirine Plus Glofitamab in Patients With Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) (SOHO 2025) - P1 | "Lonca-Glofit in R/R B-NHL showed a manageable/consistent safety profile and encouraging efficacy in heavily pretreated aggressive lymphoma patients. Results suggest Lonca complements Glofit's mechanism and provides additive efficacy. Funding: ADC Therapeutics SA and Sobi; medical writing: Citrus Health Group."

Clinical • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4 • CD8 • IL6

Deep responses following treatment with loncastuximab tesirine (WM-NET1 trial) in patients with Relapsed/Refractory including those withhigh-risk, TP53-altered Waldenström macroglobulinemia. (ASH 2025) - P2 | "Our findings from this ongoing, prospective trial demonstrate a high VGPR/CR rate of 71% inheavily pre-treated WM. Notable, is the VGPR/CR rate of 89% in high-risk patients with TP53ALT WM. Nounexpected toxicities have been seen in this trial."

Clinical • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CA6 • CXCR4 • MYD88 • TP53

PRAC adopted an updated RMP (version 3.1) for Zynlonta, removing the Category 3 study ADCT-402-107 (LOTIS-10) as an additional pharmacovigilance activity. (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 8 – 11 Jun 2026: The RMP was considered acceptable, with risk management maintained through routine pharmacovigilance and PSUR monitoring. The variation will be further considered by CHMP for adoption of an opinion. [AI generated summary]

PRAC • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

Phase Ib Open‑Label Study of Loncastuximab Tesirine in Combination With Other Anticancer Agents in Patients With Relapsed or Refractory B‑Cell Non‑Hodgkin Lymphoma (LOTIS‑7) (SOHO 2023) - P1b | "Design: Planned arms include Lonca + polatuzumab vedotin (Pola; arm C), glofitamab (arm E), or mosunetuzumab (arm F). Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting."

Clinical • Combination therapy • P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

FIL_COLUMN: Consolidation With Loncastuximab Tesirine After a Short Course of Immunochemotherapy in BTKi-treated (or Intolerant) Relapsed/Refractory Mantle Cell Lymphoma Patients. (clinicaltrials.gov) - P2 | N=49 | Active, not recruiting | Sponsor: Fondazione Italiana Linfomi - ETS | Trial primary completion date: Mar 2026 ➔ Mar 2027 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CD19

The LOTIS-7 Phase 1b trial evaluating ZYNLONTA in combination with the bispecific antibody glofitamab (COLUMVI) in patients with r/r DLBCL completed enrollment of 100 patients at the selected 150 µg/kg starting dose of ZYNLONTA. (PRNewswire) - "The Company submitted LOTIS-7 data to ASH, which continues to demonstrate potential best-in-class bispecific combination data with a safety profile generally consistent with prior LOTIS-7 disclosures. The Company is preparing to submit the complete trial results for publication, which will then be submitted to compendia. The Company is also evaluating a regulatory pathway for this combination and plans to submit for Breakthrough Therapy designation (BTD) this year."

Breakthrough therapy • Enrollment closed • P1 data • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma

Investigator-Initiated trials (IITs) evaluating ZYNLONTA in additional B-cell malignancies continue to advance. (PRNewswire) - "Updated MZL data were submitted to ASH and the Company anticipates presentation of this data before the end of the year, with publication and compendia submission to follow. The Company also anticipates presentation of updated FL data in Q2 2027. The Company intends to assess potential regulatory pathways and plans to submit for BTD for MZL."

Breakthrough therapy • P2 data • Follicular Lymphoma • Marginal Zone Lymphoma

LOTIS-5 pre-sBLA meeting held; Company evaluating regulatory path forward. (PRNewswire) - "During this meeting, the FDA noted substantial concerns regarding the benefit-risk or verification of clinical benefit observed in this trial based on the imbalance in Grade 5 events, when assessed in the context of a marginal treatment benefit. Following this meeting, the Company is assessing the best regulatory path forward and plans to provide an update on regulatory strategy and timing in the near future. ZYNLONTA remains available under accelerated approval as a monotherapy in 3L+ DLBCL and the Company plans to continue to commercialize in this setting."

FDA event • Diffuse Large B Cell Lymphoma

A real-world pharmacovigilance analysis of cardiac adverse events associated with newer antibody-drug conjugates for hematological malignancies in adults: A disproportionality analysis from FDA adverse event reporting system database. (PubMed, J Oncol Pharm Pract) - "We conducted a pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) to identify CAEs associated with ADCs for hematologic malignancies and assess high-risk subpopulations.MethodsWe analyzed five ADCs: gemtuzumab ozogamicin, inotuzumab ozogamicin, polatuzumab vedotin, loncastuximab tesirine, and belantamab mafodotin...Disproportionality analysis used four metrics: reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and Empirical Bayes Geometric Mean (EBGM), with signals defined as significant across all.ResultsCAEs represented 3.2% of adverse events (AEs) for gemtuzumab, 2.0% for polatuzumab, 0.96% for inotuzumab, and 1.3% for belantamab...These results support the need for drug labeling and cardiac monitoring in high-risk groups. Prospective studies should inform evidence-based recommendations regarding ADC administration and cardiotoxicity risk."

Adverse events • Journal • Real-world evidence • Cardiovascular • Heart Failure • Hematological Disorders • Hematological Malignancies • Myocardial Ischemia • Oncology