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DRUG:

Arzerra (ofatumumab)

i
Other names: HuMax-CD20, GSK1841157, OMB157, GSK-1841157, OMB-157, HuMax CD20, GSK 1841157, HuMaxCD20, OMB 157
Company:
GSK, Genmab, Novartis
Drug class:
CD20 inhibitor
Related drugs:
14d
Sequential Efgartigimod and Ofatumumab Therapy for Generalized Myasthenia Gravis (ChiCTR2400084937)
P2, N=30, Completed, Peking University People's Hospital; Peking University People's Hospital | Not yet recruiting --> Completed
Trial completion
|
Arzerra (ofatumumab)
27d
Ofatumumab for Minimal Residual Disease (MRD) and Maintenance Therapy (clinicaltrials.gov)
P2, N=4, Terminated, M.D. Anderson Cancer Center | N=44 --> 4 | Trial completion date: Jul 2025 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Oct 2024; Slow Accrual
Enrollment change • Trial completion date • Trial termination • Trial primary completion date
|
CD20 (Membrane Spanning 4-Domains A1)
|
Arzerra (ofatumumab)
1m
A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL (clinicaltrials.gov)
P2, N=27, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | N=50 --> 27
Trial completion • Enrollment change
|
CD19 (CD19 Molecule) • CCND1 (Cyclin D1) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
Chr t(11;14) • CCND1 overexpression
|
Zydelig (idelalisib) • Arzerra (ofatumumab)
2ms
Ofatumumab, High Dose Methylprednisolone, Ofatumumab and Lenalidomide Consolidative Therapy for Untreated CLL/SLL (clinicaltrials.gov)
P2, N=45, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Sep 2024 --> Mar 2025
Trial completion date
|
CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule)
|
lenalidomide • Arzerra (ofatumumab)
2ms
Ofatumumab for the treatment of optic neuritis associated with neuromyelitis optica spectrum disorder (ChiCTR2400086835)
P4, N=10, Recruiting, Chinese PLA General Hospital & Chinese PLA Medical School; Chinese PLA General Hospital & Chinese PLA Medical School
New P4 trial
|
Arzerra (ofatumumab)
4ms
Ofatumumab for Minimal Residual Disease (MRD) and Maintenance Therapy (clinicaltrials.gov)
P2, N=44, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025
Trial completion date • Trial primary completion date • Minimal residual disease
|
CD20 (Membrane Spanning 4-Domains A1)
|
Arzerra (ofatumumab)
5ms
Local radiotherapy and measurable residual disease-driven immunotherapy in patients with early-stage follicular lymphoma (FIL MIRO): final results of a prospective, multicentre, phase 2 trial. (PubMed, Lancet Haematol)
Local radiotherapy is frequently not associated with the eradication of follicular lymphoma. An MRD-driven, anti-CD20 monoclonal antibody consolidation enables molecular remission to be reached in almost all patients and is associated with a reduced incidence of relapse over time. A clinical advantage of an MRD-driven consolidation is therefore suggested.
P2 data • Journal
|
BCL2 (B-cell CLL/lymphoma 2)
|
Arzerra (ofatumumab)
6ms
Enrollment open
|
Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • Besponsa (inotuzumab ozogamicin) • vincristine • Arzerra (ofatumumab) • Truxima (rituximab-abbs) • mercaptopurine • Starasid (cytarabine ocfosfate)
7ms
Enrollment closed
|
Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • Besponsa (inotuzumab ozogamicin) • vincristine • Arzerra (ofatumumab) • Truxima (rituximab-abbs) • mercaptopurine • Starasid (cytarabine ocfosfate)
8ms
Trial completion date
|
BCL2 (B-cell CLL/lymphoma 2) • CD4 (CD4 Molecule)
|
bortezomib • bendamustine • Arzerra (ofatumumab) • Belrapzo (bendamustine RTD)
8ms
Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia (clinicaltrials.gov)
P2, N=53, Active, not recruiting, Northwestern University | Trial completion date: May 2023 --> May 2027
Trial completion date
|
CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule) • CD52 (CD52 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
CD19 expression
|
Campath (alemtuzumab) • Arzerra (ofatumumab)
8ms
Long-term follow up of the combination of ofatumumab, high-dose methylprednisolone, and lenalidomide for untreated chronic lymphocytic leukemia with biomarker analysis. (PubMed, Clin Lymphoma Myeloma Leuk)
The combination of ofatumumab, HDMP, and lenalidomide was effective and relatively well tolerated in treatment-naive CLL/SLL. Its role in the frontline setting remains unclear given the current available and effective treatment options.
Journal
|
IGH (Immunoglobulin Heavy Locus)
|
Chr del(11q)
|
lenalidomide • Arzerra (ofatumumab)
10ms
The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma. (PubMed, Cancers (Basel))
Our data show that S1P signaling can modulate macrophage recruitment and tumor cell killing by anti-CD20 monoclonal antibodies in DLBCL. The administration of S1PR1 inhibitors could enhance the phagocytosis of tumor cells and improve outcomes for patients.
Journal • Tumor cell
|
S1PR1 (Sphingosine-1-Phosphate Receptor 1)
|
Rituxan (rituximab) • Arzerra (ofatumumab)
10ms
Trial completion
|
CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • IGH (Immunoglobulin Heavy Locus) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
Chr t(11;14) • CD20 expression
|
cytarabine • doxorubicin hydrochloride • cyclophosphamide • vincristine • Arzerra (ofatumumab) • Starasid (cytarabine ocfosfate) • dexamethasone injection • methotrexate IV
11ms
Maintenance therapy for chronic lymphocytic leukaemia. (PubMed, Cochrane Database Syst Rev)
There is currently moderate- to very low-certainty evidence available regarding the benefits and harms of maintenance therapy in people with CLL. Anti-CD20 mAbs maintenance improved PFS, but also increased grade 3/4 AEs and all AEs. IMiD maintenance had a large effect on PFS, but also increased grade 3/4 AEs. However, none of the above-mentioned maintenance interventions show differences in OS between the maintenance and control groups. The effects of alemtuzumab maintenance are uncertain, coupled with a warning for drug-related infectious toxicity. We found no studies evaluating other novel maintenance interventions, such as B-cell receptor inhibitors, B-cell leukaemia-2/lymphoma-2 inhibitors, or obinutuzumab.
Review • Journal
|
BCL2 (B-cell CLL/lymphoma 2)
|
Rituxan (rituximab) • lenalidomide • Gazyva (obinutuzumab) • Campath (alemtuzumab) • Arzerra (ofatumumab)
12ms
Ofatumumab-based Induction Chemoimmunotherapy in Previously Untreated Patients With CLL/SLL (clinicaltrials.gov)
P2, N=32, Completed, National Heart, Lung, and Blood Institute (NHLBI) | Active, not recruiting --> Completed
Trial completion
|
CD5 (CD5 Molecule)
|
cyclophosphamide • Arzerra (ofatumumab) • fludarabine IV
1year
Deep Immune Profiling Identifies Novel T-Cell Subpopulations That Influence Specific Clinical Outcomes in Chronic Lymphocytic Leukaemia (CLL) (ASH 2023)
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 • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • ICOS (Inducible T Cell Costimulator) • CD27 (CD27 Molecule)
|
Zydelig (idelalisib) • bendamustine • Arzerra (ofatumumab) • Leukeran (chlorambucil)
1year
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 • P2 data • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2)
|
BCL2 rearrangement
|
Arzerra (ofatumumab)
1year
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
|
TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • CD20 (Membrane Spanning 4-Domains A1) • KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2) • NUP214 (Nucleoporin 214)
|
TP53 mutation • KMT2A rearrangement • MLL rearrangement • TP53 expression • CRLF2 overexpression • NUP214-ABL1 fusion • ABL1 fusion
|
Rituxan (rituximab) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Arzerra (ofatumumab) • methotrexate IV
1year
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)
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.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IGH (Immunoglobulin Heavy Locus) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CD44 (CD44 Molecule) • BCL2L11 (BCL2 Like 11) • CXCL12 (C-X-C Motif Chemokine Ligand 12) • PLCG2 (Phospholipase C Gamma 2) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • CCL19 (C-C Motif Chemokine Ligand 19) • CCR7 (Chemokine (C-C motif) receptor 7) • CD200 (CD200 Molecule) • CCL2 (Chemokine (C-C motif) ligand 2) • BTLA (B And T Lymphocyte Associated) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • NFKBIE (NFKB Inhibitor Epsilon) • TMBIM6 (Transmembrane BAX inhibitor motif-containing protein 6)
|
ATM mutation • IGH mutation • CD8 expression • PLCG2 mutation • CD44 expression • CXCR4 expression
|
Imbruvica (ibrutinib) • Arzerra (ofatumumab)
1year
High Dimensional Detection of Non-Malignant B-Cells and Its Clinical Implications in Patients with Chronic Lymphocytic Leukaemia (CLL) Undergoing Frontline Therapy (ASH 2023)
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
|
CD20 (Membrane Spanning 4-Domains A1) • CD79B (CD79b Molecule) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • CD5 (CD5 Molecule) • CD27 (CD27 Molecule) • SPN (Sialophorin) • CD81 (CD81 Molecule)
|
Zydelig (idelalisib) • bendamustine • Arzerra (ofatumumab) • Leukeran (chlorambucil)
1year
Immunomodulatory Effects of Chemo-Immunotherapy ± Idelalisib in Chronic Lymphocytic Leukaemia (CLL) (ASH 2023)
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.
PD(L)-1 Biomarker • IO biomarker • Immunomodulating
|
PD-1 (Programmed cell death 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
|
PD-1 expression
|
Zydelig (idelalisib) • bendamustine • Arzerra (ofatumumab) • Leukeran (chlorambucil)
1year
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.
Preclinical • Minimal residual disease
|
CD38 (CD38 Molecule)
|
Arzerra (ofatumumab)
1year
Tumor Lysis Syndrome with CD20 Monoclonal Antibodies for Chronic Lymphocytic Leukemia: Signals from the FDA Adverse Event Reporting System. (PubMed, Clin Drug Investig)
This pharmacovigilance study on the FDA Adverse Event Reporting System detected a plausible association between CD20 monoclonal antibodies (but not CD52) and tumor lysis syndrome by assessing the adapted Bradford Hill criteria. Urgent clarification of drug- and patient-related risk factors is needed through large comparative population-based studies.
Journal • Adverse events
|
Rituxan (rituximab) • Gazyva (obinutuzumab) • Campath (alemtuzumab) • Arzerra (ofatumumab)
1year
A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL (clinicaltrials.gov)
P2, N=50, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Aug 2023 --> Jan 2024
Trial primary completion date
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CD19 (CD19 Molecule) • CCND1 (Cyclin D1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
Chr t(11;14) • CCND1 overexpression
|
Zydelig (idelalisib) • Arzerra (ofatumumab)
1year
NCI-2014-01707: Dose Adjusted EPOCH Regimen in Combination With Ofatumumab or Rituximab in Treating Patients With Newly Diagnosed or Relapsed or Refractory Burkitt Lymphoma or Relapsed or Refractory Acute Lymphoblastic Leukemia (clinicaltrials.gov)
P2, N=6, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | N=40 --> 6 | Trial completion date: Jun 2023 --> Feb 2023 | Trial primary completion date: Jun 2023 --> Feb 2023
Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
BCL2 (B-cell CLL/lymphoma 2)
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine • Arzerra (ofatumumab)
1year
Ofatumumab, High Dose Methylprednisolone, Ofatumumab and Lenalidomide Consolidative Therapy for Untreated CLL/SLL (clinicaltrials.gov)
P2, N=45, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Aug 2023 --> Aug 2024
Trial completion date • Combination therapy
|
CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule)
|
lenalidomide • Arzerra (ofatumumab)
1year
Ofatumumab for Minimal Residual Disease (MRD) and Maintenance Therapy (clinicaltrials.gov)
P2, N=44, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024
Trial completion date • Trial primary completion date • Minimal residual disease
|
CD20 (Membrane Spanning 4-Domains A1)
|
Arzerra (ofatumumab)
over1year
Monoclonal antibodies binding to different epitopes of CD20 differentially sensitize DLBCL to different classes of chemotherapy. (PubMed, Front Oncol)
We then discovered that R and ofatumumab differentially synergize with the cytotoxic and cytostatic capabilities of CHOP in separate distinct subsets of B-cell lymphoma cell lines, thereby expanding favorable immunochemotherapy interactions across a greater range of cell lines beyond those induced by R-CHOP. This finding may have immediate clinical significance because both immunochemotherapy combinations are already FDA-approved with no difference in toxicity across phase I, II, and III clinical trials. Therefore, this finding could inform a new precision medicine strategy to provide additional therapeutic benefit to patients with B-cell lymphoma using immunochemotherapy combinations that already meet the clinical standard of care.
Journal
|
CD20 (Membrane Spanning 4-Domains A1)
|
Rituxan (rituximab) • Arzerra (ofatumumab)
over1year
Anti-CD19 CAR T-cell therapy for patients with Richter syndrome: A LYSA Study from the DESCAR-T Registry (IWCLL 2023)
Indeed, chemoimmunotherapy regimens used in de novo DLBCL failed to induce a significant complete remission rate (CRR) (R-CHOP, 7%; ofatumumab-CHOP, 27%) [1,2]...Nine (60%) patients received chemo- immunotherapy, 9 (60%) had been exposed to ibrutinib including 4 (26.7%) to both ibrutinib and venetoclax (data collection ongoing for one patient)...Following CAR T-cell infusion with axi-cel (7 patients) or tisa-cel (8 patients), 8 (53.3%) patients were alive, 7 (46.6%) patients died (3 from acute toxicity with two CRS and one neurotoxicity, and 4 from disease progression)...Tocilizumab was administered to 13 (87%) patients... CD19-directed CAR T-cell therapy showed high response rates and an encouraging survival in our series of heavily pretreated RS patients. Frequency of CAR T-cell- specific adverse events was in the range of what is observed in de novo DLBCL while severity appeared higher [3,4].
Clinical • CAR T-Cell Therapy • IO biomarker
|
TP53 (Tumor protein P53) • IGH (Immunoglobulin Heavy Locus)
|
TP53 mutation • Chr del(11q)
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Rituxan (rituximab) • Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T) • Arzerra (ofatumumab) • Actemra IV (tocilizumab)
over1year
Autoimmune cytopenias in patients with chronic lymphocytic leukemia treated with targeted drugs: pooled analysis of clinical trials from the German CLL Study Group (GCLLSG) (IWCLL 2023)
With a median observation time of 38.6 months (range 1.1–76.3) a total of 981 patients treated first-line (85.4%) or relapsed/refractory (14.6%) with at least one dose of venetoclax plus CD20 antibody (n = 520), venetoclax plus BTKi (n = 297), BTKi (n = 128), or idelalisib (n = 36) were included. All patients received therapy with anti-CD20 antibody obinutuzumab (n = 685), rituximab (n = 231), or ofatumumab (n = 65)... Autoimmune cytopenias may occur with an incidence of 9% in patients with CLL treated with targeted drugs. When comparing different treatment modalities, venetoclax plus BTKi had the highest AIC incidence. Adverse risk factors for AIC were venetoclax-based treatment, advanced Binet stage, female sex and TP53 disruptions.
Retrospective data • IO biomarker
|
TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • B2M (Beta-2-microglobulin)
|
NOTCH1 mutation
|
Venclexta (venetoclax) • Rituxan (rituximab) • Gazyva (obinutuzumab) • Zydelig (idelalisib) • Arzerra (ofatumumab)
over1year
Evaluation of Candidate Theranostics for Th/Zr Paired Radioimmunotherapy of Lymphoma. (PubMed, J Nucl Med)
Using the CD20-targeting antibody ofatumumab, we evaluated chelation of Th for α-particle-emitting and radiotheranostic applications... Commercially available and novel chelators for Th showed a range of performances. The L804 chelator can be used with potent radiotheranostic capabilities for Zr/Th quantitative imaging and α-particle therapy.
Journal
|
CD20 expression
|
Arzerra (ofatumumab)
over1year
Complement system in Anti-CD20 mAb therapy for cancer: A mini-review. (PubMed, Int J Immunopathol Pharmacol)
Therapy with anti-CD20 monoclonal antibodies (mAbs), for example, rituximab and ofatumumab, is a well-established treatment for lymphoid malignancies, and CDC is one of the main mechanisms underlying their anti-cancer activity. Previous studies have reported that a gain-of-function in a certain complement component can boost the cytolytic activity of anti-CD20 mAbs. Through reviewing the literature on complement system control and anti-CD20 mAbs, this article aims to provide a thorough understanding of the potential of targeting complement components in lymphoma therapy.
Review • Journal
|
Rituxan (rituximab) • Arzerra (ofatumumab)
over1year
Ofatumumab regimens in chronic lymphocytic leukemia: a meta-analysis. (PubMed, Ann Hematol)
Also, ofatumumab had no statistically significant improvement in the OS of patients with CLL. Thus, ofatumumab-based therapies for CLL patients could be improved by other combinational-based regimens.
Retrospective data • Review • Journal
|
Arzerra (ofatumumab)
over1year
GENETIC MARKERS AND OUTCOME OF CLL PATIENTS IN COMBINED TIME-LIMITED TREATMENT WITH ANTI-CD20 ANTIBODY + IBRUTINIB, IDELALISIB OR VENETOCLAX IN THE GCLLSG CLL2-BAG, -BCG, -BIG AND -BIO PHASE-II TRIALS (EHA 2023)
Four phase-2 trials of the German CLL Study Group evaluated time-limited combination regimens in treatment-naïve or relapsed/refractory CLL: BAG (venetoclax-obinutuzumab), BCG (idelalisib- obinutuzumab), BIG (ibrutinib-obinutuzumab) and BIO (ibrutinib-ofatumumab), with or without initial debulking with bendamustine. Genetic risk factors such as the IGHV mutation status remain significant prognostic factors for PFS in the context of time-limited treatment with targeted drugs. Acquisition of high-risk markers was rare and resistance mutations were only acquired in 2 of 44 cases. Chronic lymphocytic leukemia, ibrutinib, Prognostic factor, Venetoclax
Clinical • P2 data • IO biomarker
|
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • SF3B1 (Splicing Factor 3b Subunit 1) • IGH (Immunoglobulin Heavy Locus) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • BIRC3 (Baculoviral IAP repeat containing 3) • POT1 (Protection of telomeres 1) • NFKBIE (NFKB Inhibitor Epsilon)
|
TP53 mutation • Chr del(17p) • Chr del(11q) • SF3B1 mutation • IGH mutation • BCL2 mutation
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Zydelig (idelalisib) • bendamustine • Arzerra (ofatumumab)
over1year
IBRUTINIB FOR TREATMENT OF RELAPSED-REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA: A MATCHING-ADJUSTED INDIRECT COMPARISON OF 3 RANDOMIZED PHASE 3 TRIALS (EHA 2023)
Within R/R CLL, single-agent ibrutinib was evaluated in 3 randomized phase 3 trials: RESONATE (vs ofatumumab), ALPINE (vs zanubrutinib), and ELEVATE-RR (vs acalabrutinib in patients with del(11q) or del(17p) mutations). In phase 3 randomized trials in R/R CLL, continuous ibrutinib treatment was associated with robust PFS and ORR benefits. Ibrutinib outcomes were consistent between RESONATE and ELEVATE-RR; however, significant differences in the performance of ibrutinib within ALPINE were identified. Indirect comparisons have limitations,since each trial, protocol, and patient profile are unique; however, these results highlight the need for further research on which elements of protocol design, center selection, or treatment delivery may lead to a significant impact on the performance of a given BTKi in clinical trials.
Clinical • P3 data
|
Chr del(11q) • Chr del(17p) + Chr del(11q)
|
Imbruvica (ibrutinib) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • Arzerra (ofatumumab)
over1year
SAFETY AND TREATMENT ADHERENCE WITH ACALABRUTINIB IN VERY OLD (≥80Y) AND/OR FRAIL PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) - INTERIM SAFETY ANALYSIS OF THE ONGOING PHASE-II CLL-FRAIL TRIAL (EHA 2023)
In the previously treated cohort, prior lines of treatment included chemoimmunotherapy in 73% and ibrutinib + obinutuzumab + venetoclax, bendamustine + ibrutinib + ofatumumab and obinutuzumab + venetoclax in 9% of patients each. The first interim analysis of this international phase II study evaluating treatment with acalabrutinib in very old and/or frail patients with CLL did not show unexpected safety signals in comparison to prior published data. Comorbidities, Chronic lymphocytic leukemia, Clinical trial, Elderly
Clinical • P2 data • IO biomarker • Adherence
|
IGH (Immunoglobulin Heavy Locus)
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Calquence (acalabrutinib) • bendamustine • Arzerra (ofatumumab)
over1year
HYPER-CVAD WITH BLINATUMOMAB AND INOTUZUMAB OZOGAMICIN FOR PATIENTS WITH NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-NEGATIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE II STUDY (EHA 2023)
Pts received hyper-CVAD alternating with high-dose methotrexate and cytarabine 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)...In pts with newly diagnosed Ph-negative B-cell ALL receiving hyper-CVAD with sequential blinatumomab, the addition of INO is safe and may improve survival. Acute lymphoblastic leukemia, Clinical trial, Phase II
Clinical • P2 data
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ABL1 (ABL proto-oncogene 1) • CD20 (Membrane Spanning 4-Domains A1) • KMT2A (Lysine Methyltransferase 2A) • NUP214 (Nucleoporin 214)
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KMT2A rearrangement • MLL rearrangement • NUP214-ABL1 fusion • ABL1 fusion
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Rituxan (rituximab) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Arzerra (ofatumumab) • methotrexate IV
over1year
Ofatumumab for Minimal Residual Disease (MRD) and Maintenance Therapy (clinicaltrials.gov)
P2, N=42, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Jul 2023 | Trial primary completion date: Dec 2022 --> Jul 2023
Trial completion date • Trial primary completion date • Minimal residual disease
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CD20 (Membrane Spanning 4-Domains A1)
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Arzerra (ofatumumab)
over1year
Trial completion date • Combination therapy
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CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • IGH (Immunoglobulin Heavy Locus) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
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Chr t(11;14) • CD20 expression
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cytarabine • doxorubicin hydrochloride • cyclophosphamide • vincristine • Arzerra (ofatumumab) • Starasid (cytarabine ocfosfate) • dexamethasone injection • methotrexate IV
over1year
Ofatumumab for High-Risk Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov)
P2, N=45, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial primary completion date: Mar 2022 --> Mar 2023
Trial completion • Trial primary completion date
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IGH (Immunoglobulin Heavy Locus) • CD38 (CD38 Molecule)
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CD38 positive
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Arzerra (ofatumumab)