Arzerra (ofatumumab) / Novartis, Genmab - LARVOL DELTA

Lattice light-sheet microscopy reveals patient specific responses to CD20-directed antibodies in B cell malignancies (ASH 2025) - "Introduction CD20-targeting monoclonal antibodies (mAbs) are in clinical use and standard of care in the treatment ofhematological malignancies and autoimmune diseases, including rituximab (RTX), obinutuzumab (OBZ)or ofatumumab (OFA)...In a third patient, who was in first relapse10 years after RTX-bendamustine therapy, the highest binding was observed for 2H7 whereas OBZ againshowed the lowest activity...LLS microscopy holds significant potential to support personalization ofimmunotherapies in hematologic malignancies by identifying the most effective mAb for each individualpatient. When integrated with genetic and molecular profiling, LLS microscopy will further contribute to abroader understanding of underlying mechanisms of organism-treatment interactions."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Immunology

Transformed Waldenström macroglobulinemia is associated with poor outcomes and chemorefractory disease (ASH 2025) - "Therapy prior to HT included rituximab (R) (n=4), Ofatumumab (Ofa) alone (n=1), R/Ofa-Benda based (n=12), BTKi (n=10), proteasome inhibitor-based (n=7), FCR (n=2), R-CHOP (n=1), R-Cytoxan(n=1), idealisib (n=1), and venetoclax (n=1)...Treatment for tWMincluded R-CHOP/Pola-R-CHP (70%), dose intense therapies [R-EPOCH, R-CODOX, HyperCVAD, RICE](17%), and 14% received other regimens [R-MPV, R-Cytoxan, R-CEPP]... Our single-center experience recapitulates the poor OS of tWM patients and reinforces theneed for further advances for this vulnerable population. The median time to relapse was less than 12months, suggestive of chemorefractory disease. The presence of CNS involvement significantlyinfluenced PFS."

IO biomarker • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • ARID1A • CD79B • CDKN2A • CXCR4 • MYD88 • TP53

The addition of inotuzumab ozogamicin to frontline hyper-CVAD and sequential blinatumomab leads to durable survival outcomes in adults with newly diagnosed B-cell acute lymphoblastic leukemia: Four-year follow-up of a phase 2 study (ASH 2025) - "Pts received Hyper-CVAD alternating with high-dosemethotrexate (MTX) and cytarabine (Ara-C) for up to 4 cycles, followed by 4 cycles of blina...Ofatumumab 2000 mg or rituximab 375 mg/m2 wasadministered in pts with CD20>1%...Pts received 12 ITchemotherapies and ursodiol.ResultsAs of July 2025, 75 pts were treated (38 without InO [cohort 1] and 37 with InO [cohort 2])...With death as a competing risk, the 4-year cumulative incidenceof relapse (CIR) rate was 18% for cohort 1 and 8% for cohort 2 (p = 0.177) and 4-year cumulativeincidence of death without relapse rate was 2% and 0% (p = 0.083), respectively.MVA for OS and EFS demonstrates that the administration of InO was the only favorable predictive factorfor OS (no InO HR 12.5; p=0.02) and borderline for EFS (no InO HR 3.15; p=0.06).There were no episodes of veno-occlusive disease.ConclusionFor pts with ND Ph-negative B-ALL, the addition of InO to Hyper-CVAD plus blina leads to promisingsurvival outcomes with the..."

Clinical • P2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hepatology • Leukemia • CD20 • CD22 • CRLF2 • KMT2A

Hyper-CVAD versus hyper-CVAD plus blinatumomab for adult patients with newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia: A propensity score analysis (ASH 2025) - P2 | "We,therefore, conducted a propensity matched analysis comparing the outcomes of pts with ND Ph-negative(-) B-ALL who received HCVAD vs. HCVAD and sequential blina.MethodsPts with ND Ph- B-ALL 18-60 years who received HCVAD with/without an anti-CD20 antibody(rituximab/ofatumumab) (NCT01363128) or HCVAD and sequential blina with/without inotuzumab(NCT02877303) were included...The duration of maintenance was reducedfrom 30 cycles of POMP (6-mercaptopurine, vincristine, methotrexate, prednisone) to 12 cycles with 1course of blina every third course for a total of 3 courses of blina...For matched Ph-like, the 3- and 5-year EFS rates were 63% and 50% vs. 83% and83% for HCVAD vs. HCVAD/blina, respectively (p=0.271), with 3- and 5-year OS rates of 63% vs. 100%respectively (p=0.099).MVA identified age (EFS HR 1.02 p=0.003 OS HR 1.024 p=0.013), smoking (EFS HR 1.8 p=0.003 OS HR 1.8p=0.01), BMI (EFS HR 1.06 p<0.001 OS HR 1.04 p=0.017), ECOG (EFS HR 2.1 p=0.01), KMT2Ar (EFS..."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • KMT2A

Relative Efficacy of Systemic Treatments for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: A Network Meta-Analysis According to 17p Deletion/TP53 Mutations (ASH 2024) - "Ibrutinib was used as reference treatment.Results : Twelve trials involving 4,437 patients and 13 treatment options were included in the meta-analysis : three Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two BTK inhibitors combined with other treatments (ibrutinib plus rituximab plus bendamustine [RB] and ibrutinib plus rituximab), two phosphoinositide 3-kinase (PI3K) inhibitors (idelalisib and duvelisib), three PI3K inhibitors combined with other treatments (idelalisib plus ofatumumab, idelalisib plus RB, idelalisib plus rituximab), three anti-CD20-based treatment (RB, ofatumumab, and rituximab), and one BCL-2 inhibitor (venetoclax plus rituximab). In the 17p deletion/TP53 mutation subgroup, zanubrutinib demonstrated the most favorable efficacy (HR 0.52, 95% CI 0.31-0.88 versus ibrutinib) with the highest SUCRA value (97%). For patients without these mutations, venetoclax plus rituximab was the most effective (HR 0.49, 95% CI..."

IO biomarker • Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

Monoclonal Antibodies as a Breakthrough in Personalised Leukaemia Therapy: What Pharmacists and Doctors Should Know. (PubMed, Pharmacy (Basel)) - "The drugs considered include blinatumomab, inotuzumab ozogamicin, gemtuzumab ozogamicin, rituximab, ofatumumab, obinutuzumab, and alemtuzumab. The review offers a comprehensive resource to equip pharmacists and other clinicians to optimise mAb therapy and promote the safe use of these novel therapies."

Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Updated Results from a Phase II Study Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-Cell Acute Lymphoblastic Leukemia (ASH 2024) - "Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C (dose reduced to 500 mg/m2 of MTX and 1 g/m2 of Ara-C) and to 2 cycles of blinatumomab consolidation (4 total cycles with INO)...Conclusion In pts with newly diagnosed Ph-negative B-ALL, the addition of INO to the hyper-CVAD + blinatumomab appears to improve OS. To confirm these findings, this study now randomizes pts to hyper-CVAD + blinatumomab ± INO."

Clinical • P2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Hematological Malignancies • Hepatology • Leukemia • Oncology • CD20 • KMT2A • TP53

Updated Results from a Phase II Study of Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "Pts received hyper-CVAD alternating with high-dose methotrexate (MTX) and cytarabine (Ara-C) for up to 4 cycles, followed by 4 cycles of blinatumomab at standard doses. Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...One pt discontinued blinatumomab due to a related adverse event (grade 2 encephalopathy and dysphasia). No pts discontinued INO due to toxicity, and no cases of veno-occlusive disease have been observed."

Clinical • P2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Central Nervous System Leukemia • CNS Disorders • Hematological Malignancies • Hepatology • Leukemia • Oncology • ABL1 • CD20 • CRLF2 • KMT2A • NUP214 • TP53

Obinutuzumab in kidney transplantation: Past, present, and future. (PubMed, World J Transplant) - "Although frequently used to achieve B-cell depletion, the administration of the type 1 anti-CD20 monoclonal antibodies (mAb) rituximab (RTX) or ofatumumab (OFA) has failed to demonstrate a significant survival benefit. In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome, OBI has shown encouraging results, representing a potential evolution of the treatment of post-transplant relapsing PRD. The present review summarizes the current knowledge on OBI use in KT setting."

Journal • Review • Antibody-mediated Rejection • Glomerulonephritis • Immunology • Nephrology • Renal Disease • Transplantation

Computational design of CAR-scFv linker variants for enhanced CD20 binding against B-cell malignancies. (PubMed, Comput Biol Med) - "To address this, we employed a molecular modeling strategy using Ofatumumab, a fully human monoclonal antibody, as the framework for engineering CAR-scFvs, focusing on their binding mode, stability, and affinity towards membrane-bound CD20...Notably, binding energy calculations indicated higher binding affinity of scFv-Whitlow (-37.12 kcal/mol) for CD20 compared to scFv-G4S3 (-27.97 kcal/mol), highlighting its superior interaction dynamics. These findings position scFv-Whitlow as a promising candidate for anti-CD20 CAR-T cell therapy and provide valuable insights for the rational design of next-generation CAR constructs targeting CD20."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • CD20

Drug-induced headache reports: a comprehensive disproportionality and time-to-onset pharmacovigilance study using the FAERS database (2018-2024). (PubMed, Front Pain Res (Lausanne)) - "The drugs with the highest headache risk based on ROR included glecaprevir/pibrentasvir (ROR = 10.445), sofosbuvir/velpatasvir (ROR = 9.729), and eptinezumab-jjmr (ROR = 6.775). Top frequently reported drugs were apremilast, treprostinil, and adalimumab...Early-onset headaches (≤7days) were particularly associated with ofatumumab and fingolimod. Late-onset headaches (>90days) were linked to treprostinil and infliximab-dyyb. This large-scale pharmacovigilance study identifies multiple drugs and therapeutic classes with significant associations to headache as an ADR. These findings highlight the need for proactive headache monitoring, particularly during early treatment phases, and warrant further prospective investigations to understand mechanisms and preventive strategies."

Adverse events • Journal • Pain

Multi-Omics Exploration of Adaptive Mechanism to BTK Inhibition By Ibrutinib in CLL Identified TMBIM6/BI-1 As a Poor Prognosis Variable and Potential Therapeutic Target (ASH 2023) - P2 | " Blood samples from 28 patients from GELLC7 trial (NCT03280160, ibrutinib followed by ofatumumab consolidation) were collected before treatment (BT), and 1, 3, 6 and 12 months on treatment (at least two timepoints). Ibrutinib in T cells reduced the expression of exhaustion markers, Tregs and Tfh cells. In CLL cells, we observed a downregulation of markers related to adhesion, immunosuppression and migration, but an overexpression of TMBIM6 in CLL cells that retained migrative capacity towards CXCL12 under ibrutinib. Finally, we identified TMBIM6 expression as an independent poor prognostic factor and a potential novel target for CLL."

IO biomarker • Chronic Lymphocytic Leukemia • Oncology • Solid Tumor • BCL2L11 • BTLA • CCL19 • CCL2 • CCR7 • CD200 • CD44 • CD8 • CXCL10 • CXCL12 • CXCL13 • CXCR4 • CXCR5 • IGH • NFKBIE • PD-1 • PLCG2 • TMBIM6

Combination therapy of ofatumumab and daratumumab in patients with severe anti-NMDA receptor encephalitis. (PubMed, Front Immunol) - "We describe two adolescent female patients with severe neuropsychiatric manifestations unresponsive to standard first-line therapies, including intravenous methylprednisolone (IVMP) and intravenous immunoglobulins (IVIG). This case report demonstrates that combined treatment of ofatumumab and daratumumab therapy is well-tolerated and may represent a novel therapeutic strategy for severe NMDARE. The observed rapid serological and clinical responses highlight its potential efficacy, warranting further investigation in large cohorts."

Journal • CNS Disorders • Immunology • Psychiatry

Changes in Treatment Patterns over Time Among Real-World Patients with Follicular Lymphoma at Predominantly Community Facilities in the US (ASH 2024) - "For 2015–2018 vs 2019–2023, >80% of treatments were either R + chemo (consisting of R + bendamustine, R-CHOP, R-EPOCH, R-ICE, and similar therapies) (61% vs 58%) or R monotherapy (mono) (28% vs 25%). Chemo (mono or combination treatment with platinum-based therapies, cytarabine, vincristine, and similar), the third largest category, was unchanged (5% vs 5%). Small increases were seen in ofatumumab (OF) or obinutuzumab (OB) + bendamustine (2% vs 5%) and R + lenalidomide (R2) (1% vs 2%)...Increases were seen in R2 (2% vs 6%), OF and OB mono or with bendamustine (3% vs 7%), and lenalidomide or venetoclax mono (2% vs 5%)...Increases were seen in OF and OB monotherapy (1% vs 4%), R2 (5% vs 7%), lenalidomide or venetoclax mono (3% vs 9%), CAR-T (0% vs 2%), and tazemetostat (taz)-containing (0% vs 2%)...While mosunetuzumab, a bispecific monoclonal antibody (bsAb), was approved in late 2022, there were not sufficient pts to assess utilization...Utilization of newer therapies..."

Clinical • Real-world • Real-world evidence • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Deep Immune Profiling Identifies Novel T-Cell Subpopulations That Influence Specific Clinical Outcomes in Chronic Lymphocytic Leukaemia (CLL) (ASH 2023) - P3 | " The discovery cohort comprised pre-treatment samples from 79 CLL patients enrolled in the NCRI RIAltO trial (NCT01678430) who underwent factorial randomisation to ofatumumab and either bendamustine or chlorambucil, with or without idelalisib. The present study has identified three previously undescribed T-cell subpopulations that appear to influence the risk of infection, SPM, and death in patients with CLL receiving frontline chemo-immunotherapy. Further studies are warranted to validate these findings in the setting of targeted agents and in patients receiving CIT for other haematological malignancies."

Clinical • Clinical data • IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • CD27 • CD4 • CD8 • ICOS • PD-1 • TIGIT

Early-Stage Follicular Lymphoma: Learnings from the Final Analysis of the Multicenter Phase II FIL (Fondazione Italiana Linfomi) "Miro" Trial, Combining Local Radiotherapy and MRD-Driven Immunotherapy (ASH 2023) - "Pts who were MRD+ by both NEST and RQ in the BM a/o PB after IFRT or who became MRD+ during the follow-up were treated with 8 weekly doses of the anti-CD20 monoclonal antibody ofatumumab (OFA)...A consolidation strategy with more effective agent should be advisable. With these limits, a clinical advantage of the MRD-driven treatment strategy is suggested, although not largely applicable."

Clinical • IO biomarker • P2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • BCL2

High Dimensional Detection of Non-Malignant B-Cells and Its Clinical Implications in Patients with Chronic Lymphocytic Leukaemia (CLL) Undergoing Frontline Therapy (ASH 2023) - P3 | "Patients were randomly assigned to receive bendamustine or chlorambucil plus ofatumumab, with or without idelalisib. To our knowledge, this is the first study to identify correlations between the re-emergence of non-malignant B-cells following anti-CLL therapy and specific clinical endpoints such as haematopoietic recovery, serum Ig levels, TTP and OS. Although further validation is required in the context of targeted agents, our findings suggest that therapy-induced re-emergence of non-malignancy B-cells may have important biological and clinical implications in CLL."

Clinical • IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD20 • CD27 • CD5 • CD79B • CD81 • ROR1 • SPN

Immunomodulatory Effects of Chemo-Immunotherapy ± Idelalisib in Chronic Lymphocytic Leukaemia (CLL) (ASH 2023) - P3 | "Patients were randomly assigned to receive ofatumumab plus either bendamustine or chlorambucil, with or without idelalisib. CIT results in profound immune changes that persists up to 18.5 [16.1 – 22.6] months following treatment. Furthermore, the overall effect of these changes further differentiates the CLL-associated immune profile from that of HC, deepening the existing T-cell dysfunction irrespective of chemotherapy choice, or the addition of idelalisib. Our study has important potential implications for patients receiving CIT in a range of clinical settings and supports the move towards more targeted agents that are less likely to cause indiscriminate immune perturbation."

Immunomodulating • IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PD-1 • PIK3CD • TIGIT

BCMA-Directed Low Dose Alpha-Emitter Therapy Eliminates Minimal Residual Disease in a Multiple Myeloma Mouse Xenograft Model (ASH 2023) - " We conjugated a human IgG1 anti-BCMA mAb and an isotype matched nonbinding control mAb (ofatumumab), with the amine-reactive labeling agent B10-NCS to enable 211At radiolabeling... Tumor responses are encouraging with 100% of mice cured of MM after receiving low doses of BCMA targeted 211At. While we have previously demonstrated that 211At-CD38 could eliminate MM in a similar model system, in that setting fewer than 50% of mice bearing the same NCI-H929Luc tumors, and treated with 8 μCi of 211At, survived to day 150 [O'Steen S. Blood, 2019]. In contrast, here we show that 100% of mice are cured after receiving 6 μCi of 211At-BCMA-B10."

Minimal residual disease • Preclinical • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • CD38

PC-002 (Sepantronium Bromide) Enhances the Antitumor Efficacy of Anti-CD20 Antibody By CD20 Upregulation (ASH 2024) - "P493 tet-off cells were treated with tetracycline to suppress the expression of c-Myc (Myc-off)...Furthermore, mouse xenografts (RAMOS, SU-DHL-4, SU-DHL-10 and OCI-LY7) were established to evaluate the efficacy of YM155 (2 mg/kg, 168-hour-infusion) in combination with anti-CD20 antibody, including Rituximab, Ripertamab and Ofatumumab in vivo...Moreover, the up-regulation of CD20 after PC-002 treatment in RFP/Luc cells was confirmed by whole transcriptome analysis. These results indicate that PC-002 enhances the efficacy of anti-CD20 antibody by downregulating c-Myc, and support the planned clinical investigation of the combination of PC002 with an anti-CD20 antibody such as rituximab in patients with relapsed/refractory c-Myc driven Burkitt lymphoma or diffuse large B-cell lymphoma.Conclusion : In conclusion, our preclinical data highlight the potent anti-tumor effects of PC-002 in combination with anti-CD20 antibody in patients with DLBCL and BL, and warrant the planned..."

Clinical • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Orthopedics • Solid Tumor • Targeted Protein Degradation • MYC • USP7

Clinical Characteristics and Outcomes of Patients with MYD88 Positive Waldenström Macroglobulinemia: A Single Center Retrospective Analysis (ASH 2024) - "Among 240 MYD88+ pts, the most common first-line regimen was CIT (Bendamustine/Rituximab, Cyclophosphamide/Rituximab/Prednisone, Fludarabine/Rituximab) in 45.7% pts. Other first line regimens included Immunotherapy (Rituximab, ofatumumab) in 28.3 %, proteasome inhibitors-based regimen in 7.61%, BTK inhibitors in 16.3 %, and others (clinical trials, chemotherapy alone) in 2.17% pts...OS for MYD88+ pts who received first line BTKi was also lower compared to those who received CIT. *ST and DK are co-first authors"

IO biomarker • Retrospective data • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Oncology • Solid Tumor • Waldenstrom Macroglobulinemia • CXCR4 • MYD88

CALGB-50904: Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=135 | Completed | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Sep 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CD4

A Randomized, Double-Blind, Placebo-Controlled Study/ Ofatumumab Add-On Therapy in Patients with Treatment-Resistant Depression（OFA-TRD Trial） (ChiCTR) - P4 | N=60 | Not yet recruiting | Sponsor: Beijing An Ding Hospital, Capital Medical University; Beijing An Ding Hospital, Capital Medical University

New P4 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

Adherence to HBV Screening and Reactivation Prevention Protocols in Patients Receiving Anti-CD20 Treatment (ACG 2025) - "Use of prophylaxis in individuals with +sAg or -sAg/+cAb with tenofovir or entecavir was also assessed. A total of 803 patients received anti-CD20 infusions (rituximab=531, ocrelizumab=223, obituzumab=49, ofatumumab=2), 24% (n=189) of whom did not undergo appropriate sAg and cAb testing before initiation (Figure). The majority of those missing testing (88%; n=166) lacked cAb tests. Patients prescribed ocrelizumab were most likely to have incomplete HBV testing (Figure)."

Adherence • Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Failure • Rheumatology

Impact and risk factors of anti-rituximab antibodies in small-vessel vasculitis: a multicenter retrospective study (ACR Convergence 2025) - "After ARA detection, 27 patients (75%) required a change in therapy, with obinutuzumab being the most common alternative (50%), while others received cyclophosphamide, belimumab or ofatumumab. In conclusion, ARA detection is associated with younger age, Sjogren's syndrome and infusion-related reactions in cryolgobulinemia vasculitis, and with microscopic polyangiitis, renal involvement, and mononeuritis multiplex in AAV, with the RTX regimen of 1 gram on days 1 and 15 being associated with ARA detection in both vasculitis. Monitoring and switching to obinutuzumab may improve outcomes."

Retrospective data • ANCA Vasculitis • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus Nephritis • Nephrology • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Vasculitis