Polivy (polatuzumab vedotin-piiq) / Roche, Pfizer - LARVOL DELTA

Therapy Sequencing in Relapsed/Refractory MCL (ICML 2025) - P1, P1/2, P2, P3 | "Although a direct comparison between them has only been performed for ibrutinib and temsirolimus [23], covalent BTK inhibitor (cBTKi) single agent therapy has been consolidated as the standard of care after first-line CIT. Moreover, to address cBTKi failure, two anti-CD19 CAR-T cell therapy products, brexucabtagene autoleucel [20, 21] and lisocabtagene maraleucel [22], and the first noncovalent BTKi, pirtobrutinib [19], have recently been approved...Liso-cel only FDA approved; CIT, chemoimmunotherapy options include BR, R-BAC, R-CHOP, R-DHAP or R-DHAOx, R-GEMOx, paliative options (avoid bendamustine pre-CART apheresis); pirtobrutinib, available after cBTKi failure in second-line (EMA) but third-line (FDA); RM, rituximab maintenance...Orelabrutinib [18] is licensed only in China...Of note, both acalabrutinib and zanubrutinib induce lower rates of atrial fibrillation, hypertension, and bleeding compared to ibrutinib in randomized studies..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • PLCG2 • TP53

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

The Efficacy of Polatuzumab Vedotin Targeting CD79B in the Treatment of Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis. (PubMed, Int J Mol Sci) - "Further research is needed on long-term survival outcomes and optimal patient selection. PoV appears to be a promising targeted therapy option for NHL, which warrants further investigation."

Journal • Retrospective data • Review • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD79B

Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma. (PubMed, Blood) - P1, P3 | "Combining glofitamab with R-CHP-Pola chemotherapy or polatuzumab vedotin demonstrated strong synergistic anti-tumor efficacy with rapid tumor regression and reduced tumor cell proliferation. Glofitamab combination with gemcitabine/oxaliplatin (GemOx) also showed strong efficacy, enhancing intra-tumor T cell number, activation and reduced exhaustion...The preclinical investigations provide a strong foundation for ongoing and future clinical trials, emphasizing the need to tailor TCE-based combination therapies to maximize efficacy while minimizing toxicity in lymphoma treatment. NCT04408638 and NCT03467373."

IO biomarker • Journal • Preclinical • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • LAG3

DYNAMIC CHANGES OF ABSOLUTE CD4 COUNT IN PERIPHERAL BLOOD AS A PREDICTOR OF EFFICACY IN REFRACTORY/RELAPSED DLBCL HARBORING TP53 GENE MUTATIONSTREATED WITH GLOFITAMAB (ICML 2025) - "Despite these treatments (R-CHOP or Pola-R-CHP), relapse or refractory disease remains common...Given the nature of R/R DLBCL, chemo-free regimens included acalabrutinib (100 mg twice daily), zanubrutinib (160 mg twice daily), obutinib (150 mg once daily), sintilimab (200 mg per cycle), and glofitamab in combination with either polatuzumab vedotin (1.8 mg/kg) or lenalidomide (20 mg/day, days 1–14)... Chemo-free regimens incorporating glofitamab demonstrated high efficacy and good tolerability in R/R DLBCL patients with TP53 mutations. Additionally, dynamic changes in absolute CD4 count may serve as a preliminary predictor of glofitamab efficacy."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology • CD4 • TP53

A Case of Cold Agglutinin Disease With Transformation to High-Grade Lymphoma During Sutimlimab Treatment. (PubMed, Cureus) - "Subsequent chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone resulted in further improvement in anemia. This case highlights the importance of reassessing underlying conditions through BMB in cases where sutimlimab treatment is ineffective."

Journal • Autoimmune Hemolytic Anemia • B Cell Lymphoma • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • C1S

Pola-R-CHP performed well in first-line Polarix trial-ineligible and IPI 0-1 DLBCL patients : Article type: research. (PubMed, Ann Hematol) - "Polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) improved progression-free survival (PFS) of diffuse large B-cell lymphoma (DLBCL) in Polarix study...Polatuzumab vedotin was administered 1.8 mg/KG, rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 or epirubicin 70 mg/m2, all intravenously on Day 1...Dose modification of polatuzumab vedotin occurred in 4 patients in Polarix-ineligible group, and 1 in Polarix-eligible group. Pola-R-CHP performed well in first-line Polarix trial-ineligible and IPI 0-1 DLBCL patients with manageable safety."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases

"The Canada’s Drug Agency (CDA-AMC) pan-Canadian Oncology Drug Review Expert Review Committee (pERC) recommends that polatuzumab vedotin be reimbursed in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adult patients with previously untreated large B-cell lymphoma (LBCL)…" (Ottawa (ON): Canadian Agency for Drugs and Technologies in Health)

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

Polivy move closer to reimbursement (Korea Biomedical Review) - "On Wednesday, the Health Insurance Review and Assessment Service (HIRA) held a CDRC meeting and approved reimbursement criteria...Roche Korea also applied for reimbursement for Polivy’s two therapies (Pola-R-CHP and Pola-BR) indicated for treating diffuse large B-cell lymphoma (DLBCL). However, the CDRC approved reimbursement criteria only for the combination therapy of rituximab, cyclophosphamide, doxorubicin, and prednisone/prednisolone (Pola-R-CHP) for adult patients with DLBCL who have not previously received treatment."

Reimbursement • Diffuse Large B Cell Lymphoma

Lunsumio + Polivy: Regulatory approval in Japan for 2L+ DLBCL in 2025 (Roche) - H1 2025 Results

Japan approval • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

ADVANCES IN DLBCL MANAGEMENT: HIGHLIGHTS FROM CHINA (ICML 2025) - "The DEB study is the first phase III trial to show that combining tucidinostat with R-CHOP regimen is a feasible and efficacious novel approach in previously untreated DLBCL patients with DE...Another study also shows promising prospects: polatuzumab vedotin, zanubrutinib, rituximab, and lenalidomide (Pola-ZR2) regimen in unfit or frail patients with DLBCL, the CR rate was 77% (17/22), and ORR was 86% (19/22). The Pola-ZR2 regimen demonstrates promising efficacy in unfit or frail patients with DLBCL. More clinical research results will be presented at this meeting."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology • BCL2 • MYC

Roche Canada announces Polivy (polatuzumab vedotin for injection) for the First-Line Treatment of Adults With Large B-Cell Lymphoma is now Publicly Reimbursed in Québec (Canada Newswire) - "Hoffmann-La Roche Limited (Roche Canada) is pleased to announce today that Polivy (polatuzumab vedotin for injection) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adult patients with previously untreated large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high grade B-cell lymphoma, Epstein-Barr virus-positive (EBV+) DLBCL NOS, and T-cell/histiocyte rich LBCL, is now publicly funded in Québec. Roche Canada is fully committed to continuing to work with the other provincial and territorial jurisdictions to make Polivy available to patients as soon as possible through all public drug plans....on July 2, 2025, Québec approved it for public reimbursement for first-line treatment of DLBCL."

Reimbursement • Diffuse Large B Cell Lymphoma • High-grade B-cell lymphoma • Large B Cell Lymphoma

Case Report: Primary cardiac diffuse large B-cell lymphoma with sick sinus syndrome and literature review on disease management and therapeutic strategies. (PubMed, Front Oncol) - "Initial treatment with R-miniCHOP chemotherapy yielded a partial response...Prompt diagnosis and effective management are crucial in treating primary cardiac DLBCL. While the emergence of new drugs has improved the prognosis by offering higher efficacy and fewer side effects, clinicians should be vigilant about potential cardiotoxicities."

Journal • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Pneumonia • Respiratory Diseases

POLATUZUMAB VEDOTIN WITH BTK INHIBITORS AND CHEMOTHERAPY SHOWS RAPID, DEEP RESPONSES IN NON-GCB DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - "Treatment-naïve patients received Pola-BTKi-RCHP: polatuzumab vedotin (1.8 mg/kg, Day 1), a BTK inhibitor (zanubrutinib 160 mg twice daily, acalabrutinib 100 mg twice daily, or orelabrutinib 150 mg once daily, Days 1–21), rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2) on Day 1, and prednisone (100 mg daily, Days 1–5). Relapsed patients received Pola-BTKi-GemOx: polatuzumab vedotin (1.8 mg/kg, Day 1), a BTK inhibitor (same dosing), rituximab (375 mg/m2), gemcitabine (1000 mg/m2), and oxaliplatin (100 mg/m2) on Day 1... The Pola-BTKi-chemo regimen showed rapid efficacy and manageable safety in non-GCB DLBCL. Further studies on POLA and BTK inhibitor combinations are ongoing."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2 • MYC

Pomalidomide, Rituximab and Orelabrutinib Combined With Polatuzumab Vedotin in the Treatment of Newly Diagnosed Elderly Patients With DLBCL (clinicaltrials.gov) - P=N/A | N=43 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University

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

Mosunetuzumab and Polatuzumab Vedotin With Split-Dose CHP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: Medical College of Wisconsin | Initiation date: Jun 2025 ➔ Oct 2025

Trial initiation date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

EPCORE NHL-5: A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=565 | Recruiting | Sponsor: Genmab | Phase classification: P1/2 ➔ P2

Adverse events • Phase classification • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CCND1 • CD20

Marginal Zone Lymphoma: Treatment Update With a Focus on Systemic Approaches (ICML 2025) - P2, P3 | "Amongst 454 enrolled patients and with a median follow up time of over 7 years, the combination of rituximab plus chlorambucil had superior EFS (5-year EFS 68% vs. 50%) but no difference in overall survival which was excellent at 90% [17]. Other approaches added bendamustine to rituximab...Initial trials with the first-in-class covalent BTKi inhibitor, ibrutinib, were promising...The second generation covalent BTKi zanubrutinib and acalabrutinib have also been evaluated in RR MZL, with zanubrutinib receiving regulatory approval in the United States and the European Union...Unfortunately, the first-in-class PI3Kδ inhibitor, idelalisib, was associated with significant toxicities, including infection and immune-mediated complications...In MZL, there is a recent publication of parsaclisib with intriguing findings [29]...ZUMA-5 is a multicenter Phase 2 trial of axicabtegene ciloleucel (axi-cel) conducted in patients with both FL and MZL [30]...Several CD20xCD3 BsAbs,..."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hairy Cell Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Splenic Marginal Zone Lymphoma • CD5 • CRBN • MME • MYD88 • PIK3CD

GUIDANCE 05: A PROSPECTIVE RANDOMIZED STUDY ON GENOTYPE-GUIDED TARGETED AGENTS WITH POLA-RCHP(POLA-RCHP-X) VERSUS POLA-RCHP IN UNTREATED DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - P2 | "The Phase III POLARIX study demonstrated that Polatuzumab (Pola)-R-CHP extends progression-free survival (PFS) compared to R-CHOP, with a similar safety profile, suggesting broader patient benefit...Arm A: MCD-like, BN2-like, N1-like receive zanubrutinib + Pola-RCHP; TP53 mutations receive decitabine + Pola-RCHP; EZB-like MYC+/-, ST2-like, NOS receive lenalidomide + Pola-RCHP...Exploratory endpoints include PFS, EFS, CR rate, ORR, and OS within each genetic subtyping group. The study, set to commence in March 2025, will involve approximately 20 sites worldwide."

Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TP53

EFFICACY AND SAFETY OF POLATUZUMAB VEDOTIN, ZANUBRUTINIB AND RITUXIMAB IN UNTREATED ELDERLY AND FRAIL DLBCL PATIENTS: A PROSPECTIVE PHASE 2 CLINICAL TRIAL (ICML 2025) - P2 | "Pola-ZR showed preliminary efficacy in untreated elderly and frail DLBCL patients in this prospective clinical trial. Lung infection was marginally reduced under mandatory prophylaxis for PJP. Safety profiles were manageable."

Clinical • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology

T-Cell Redirecting Strategies in Large B-Cell Lymphoma and Follicular Lymphoma (ICML 2025) - "The randomized STARGLO trial compared the combination of glofitamab with gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx, meeting its primary endpoint of OS in favor of the experimental arm (HR 0.62 [95% CI 0.43–0.88])...Other treatment options to consider in this R/R patient population are tafasitamab/lenalidomide [107], loncastuximab tesirine [108] and rituximab-bendamustine-polatuzumab [109], amongst others...Three CAR-T constructs are available based on Phase 2, single-arm trials, namely ZUMA-5 (axi-cel), ELARA (tisa-cel), and TRANSCEND-FL (liso-cel)...Mosunetuzumab, epcoritamab and odronextamab received regulatory approval (U.S...She started treatment with a bispecific antibody, aiming to carry out her first imaging assessment after three cycles. Permission to Reproduce Material From Other Sources The author has nothing to report."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD19

Incidence of Clinically Significant Neutropenia and Complications Related to Antibody-Drug Conjugates: A Real-Word Study at University of California (MASCC-ISOO 2025) - "Methods A multi-center retrospective study utilized UC Health Data Warehouse records of patients receiving at least one dose of the ten most-used ADCs between January 2012 and August 2024: fam-trastuzumab deruxtecan, ado-trastuzumab emtansine, brentuximab vedotin, sacituzumab govitecan, enfortumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, polatuzumab vedotin, belantamab mafodotin, and tisotumab vedotin. Patient distribution and primary outcomes Table 3. Secondary outcomes Conclusions The most commonly used ADCs in contemporary practice, such as fam-trastuzumab deruxtecan, and ado-trastuzumab emtansine, were associated with reasonably low rates of febrile neutropenia and related events."

Clinical • Anemia • Febrile Neutropenia • Neutropenia • Oncology

PREDICTORS FOR ANTIBODY-DRUG CONJUGATES (ADCS) ASSOCIATED CLINICALLY SIGNIFICANT NEUTROPENIA AT UNIVERSITY OF CALIFORNIA HOSPITALS (MASCC-ISOO 2025) - "The study focused on the ten most commonly used ADCs: fam-trastuzumab deruxtecan, ado-trastuzumab emtansine, brentuximab vedotin, sacituzumab govitecan, enfortumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, polatuzumab vedotin, belantamab mafodotin, and tisotumab vedotin. Conclusions Selected ADCs are associated with significant risks of severe neutropenia. These findings highlight the importance of identifying patients who are predisposed to these adverse effects and implementing tailored management strategies."

Clinical • Anemia • Breast Cancer • Hepatology • Liver Failure • Neutropenia • Oncology

CC-220-DLBCL-001: Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma (clinicaltrials.gov) - P1 | N=174 | Recruiting | Sponsor: Celgene | Trial completion date: Jun 2027 ➔ Dec 2028 | Trial primary completion date: Jun 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

POLATUZUMAB-CONTAINING REGIMENS AS BRIDGE TO CAR-T: INSIGHTS FROM THE ITALIAN CAR T-SIE STUDY (ICML 2025) - "Polatuzumab vedotin (PV) combined with rituximab (R) ± bendamustine (BR) is effective in LBCL relapsed/refractory to at least a previous line of therapy, being promising for candidates for CART... This multicenter, observational, retrospective study was conducted on the Italian CART-SIE study, including patients diagnosed with refractory or relapsed LBCL and treated with commercial anti-CD19 CART (axi-cel, tisa-cel, liso-cel)... In this multicenter, retrospective study PV-R and PV-BR were efficacious in controlling the tumor prior to CART, with similar responses and immune cell-associated toxicities after infusion. The higher incidence of hematological toxicities in the PV-BR group, combined with the resulting potential delay in CART infusion highlights the PV-R regimen as the treatment of choice, paving the way for a chemo-sparing regimen as a bridge to CART."

B Cell Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma