- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca, Imbruvica (ibrutinib) / AbbVie, J&J
Clinical, Retrospective data, Review, Journal: Molecular-Biology-Driven Frontline Treatment for Chronic Lymphocytic Leukemia: A Network Meta-Analysis of Randomized Clinical Trials. (Pubmed Central) - Jul 2, 2023
Finally, considering that NMA and SUCRA work for single endpoints only, we performed a principal component analysis to recapitulate in a cartesian plane the SUCRA profiles of each schedule according to the results obtained in each sub-analysis, confirming again the superiority of aCD20/BTKi or BCL2i combinations in a first-line setting. Overall, here we demonstrated that: (1) a chemotherapy-free regimen, such as the combination of aCD20 with a BTKi or BCL2i, should be the preferred treatment choice despite biological/molecular characteristics (preferred regimen O-acala); (2) there is less and less room for chemotherapy in the first line treatment of CLL.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Biomarker, Journal: Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy. (Pubmed Central) - Jul 2, 2023
To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment...Results suggest that the efficacy of anti-CD20 mAb therapy may be influenced by B cell developmental status as well as polymorphism in the MKL1 gene. A clinical benefit may be achieved by pretreatment with corticosteroids such as prednisolone followed by mAb therapy.
- |||||||||| Review, Journal: Waldenstr (Pubmed Central) - Jun 28, 2023
Many of the abovementioned drugs do not have official registration for WM and can be administrated with the consent of the health care provider only. Thus, this work brings evidence of their efficacy.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Trial primary completion date: Obinutuzumab, Venetoclax, and Lenalidomide in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - Jun 27, 2023
P1, N=22, Active, not recruiting,
Thus, this work brings evidence of their efficacy. Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Journal, HEOR: Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit CLL patients. (Pubmed Central) - Jun 26, 2023
These improvements were comparable for patients receiving venetoclax consolidation and patients in whom treatment could mostly be discontinued (93% based on negative MRD in MRD-guided arm). Collectively, front-line fixed-duration Ven-O improves overall PROs in older, unfit CLL patients with and without geriatric impairments.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Imbruvica (ibrutinib) / AbbVie, J&J
Journal: Final analysis of the CLL2-GIVe trial (obinutuzumab, ibrutinib, and venetoclax) in untreated CLL with del(17p)/TP53mut. (Pubmed Central) - Jun 26, 2023
P2
In conclusion, the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with high-risk CLL with a manageable safety profile. Clinical Trial registry: CLL2-GIVe (NCT02758665).
- |||||||||| Review, Journal: Lupus Nephritis: New and Emerging Biologic and Targeted Therapies. (Pubmed Central) - Jun 26, 2023
In this context, we discuss (1) drugs with the potential to achieve these treatment goals by modulating SLE activity as the driving force for LN (e.g., belimumab, obinutuzumab, anifrolumab, and others); (2) drugs with SLE-non specific renoprotective effects by targeting non-immune mechanisms of LN progression (dapagliflozin, empagliflozin); and (3) drugs with dual immunosuppressive and antiproteinuric effects (voclosporin). Increasing the number of possible drug options will help to improve the management of LN in terms of efficacy and safety, and enable a more personalized treatment approach.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
Trial completion date, Trial primary completion date: Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) - Jun 22, 2023
P2, N=168, Recruiting,
Increasing the number of possible drug options will help to improve the management of LN in terms of efficacy and safety, and enable a more personalized treatment approach. Trial completion date: Jul 2023 --> Jul 2026 | Trial primary completion date: Jul 2023 --> Jul 2026
- |||||||||| CAR T-Cell Therapy and Bispecific Antibodies in Mantle Cell Lymphoma (LEVEL 3, GENERAL ASSEMBLY) - Jun 21, 2023 - Abstract #SOHO2023SOHO_225;
Trial completion date: Apr 2024 --> Apr 2029 Specifically, we have noted improved outcomes with use of covalent BTKi in this space with durability noted especially in those who have obtained a complete remission (CR).2
- |||||||||| Novel Combinations in Indolent Lymphoma (LEVEL 3, GENERAL ASSEMBLY) - Jun 21, 2023 - Abstract #SOHO2023SOHO_202;
Finally, due to the role played by epigenetic changes in the pathophysiology of iNHL, the combination of tazemetostat, an EZH2 inhibitor approved for the treatment of relapsed FL, has also been investigated...Beyond the novel combinations outlined in this abstract, multiple trials are currently investigating agents with alternative mechanism of actions, including anti-CD19 monoclonal antibodies, anti-CD79b antibody-drug conjugates and novel immunomodulatory agents S111 and allogeneic cellular therapies. The therapeutic landscape of iNHL is soon to significantly change.
- |||||||||| How We Developed a Curative Therapy for CLL and Stopped Using It (Level 3, Hall B3) - Jun 21, 2023 - Abstract #SOHO2023SOHO_172;
Recent radical changes in the therapeutic landscape for CLL have led to current global treatment guidelines recommending the use of various highly effective targeted agents as frontline therapy,1,2 displacing previous chemoimmunotherapy (CIT) regimens such as fludarabine/ cyclophosphamide/rituximab (FCR)...In the late 1980's, three functionally similar agents related to purine nucleoside analogues entered clinical development; deoxycoformycin (DCF), 2-chlorodeoxy-adenosine (cladribine; 2-CdA) and 2-F-ara-adenosinemonophosphate (fludarabine; F). The first major report of F in relapsed/refractory CLL by Keating was truly remarkable in describing a 13% CR rate (overall response rate 57%).3 Cheson summarized this period as a "therapeutic beauty contest" among the three agents, that F ultimately emerged from victorious and became the foundational agent for subsequent combination development.4 As a single agent in frontline CLL, F improved PFS compared to chlorambucil (20 vs 14 months) and attained a CR rate of 20%.5 Elegant work in Plunkett's lab at MD Anderson established the synergy between F and DNA-damaging agents such as cyclophosphamide via inhibition of DNA repair,6 and at least 3 frontline trials have shown the superiority of the FC combination over single agent F, with CR rates as high as 39%, but modest overall survival impact.7 The new century brought the first therapeutic monoclonal antibody in cancer (rituximab; antiCD20) to be bravely applied in CLL by Byrd and O'Brien showing modest single agent activity, developing a safe infusion schedule to mitigate reactions, and establishing a dose response curve above the standard 375 mg/m2 lymphoma dose.8 Further laboratory studies showed bi-directional synergistic cytotoxicity with FC and R, both directly and through reduction in levels of surface complement defense proteins by F, and reduction in anti-apoptotic BCL2 protein levels by R.9 The resultant FCR regimen was pioneered at MD Anderson10 and subsequently shown in randomized trials in both frontline and relapse settings to deliver improved overall survival compared to FC and attain CR rates of up to 72% and the unprecedented attainment of uMRD (<10
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
Debate: Stop vs Continue VenG: MRD+ at 1 Year of VenG: Stop Therapy (Level 3, Hall B3) - Jun 21, 2023 - Abstract #SOHO2023SOHO_170;
The first major report of F in relapsed/refractory CLL by Keating was truly remarkable in describing a 13% CR rate (overall response rate 57%).3 Cheson summarized this period as a "therapeutic beauty contest" among the three agents, that F ultimately emerged from victorious and became the foundational agent for subsequent combination development.4 As a single agent in frontline CLL, F improved PFS compared to chlorambucil (20 vs 14 months) and attained a CR rate of 20%.5 Elegant work in Plunkett's lab at MD Anderson established the synergy between F and DNA-damaging agents such as cyclophosphamide via inhibition of DNA repair,6 and at least 3 frontline trials have shown the superiority of the FC combination over single agent F, with CR rates as high as 39%, but modest overall survival impact.7 The new century brought the first therapeutic monoclonal antibody in cancer (rituximab; antiCD20) to be bravely applied in CLL by Byrd and O'Brien showing modest single agent activity, developing a safe infusion schedule to mitigate reactions, and establishing a dose response curve above the standard 375 mg/m2 lymphoma dose.8 Further laboratory studies showed bi-directional synergistic cytotoxicity with FC and R, both directly and through reduction in levels of surface complement defense proteins by F, and reduction in anti-apoptotic BCL2 protein levels by R.9 The resultant FCR regimen was pioneered at MD Anderson10 and subsequently shown in randomized trials in both frontline and relapse settings to deliver improved overall survival compared to FC and attain CR rates of up to 72% and the unprecedented attainment of uMRD (<10 Results The majority of patients who undergo treatment with venetoclax plus the CD20 antibody obinutuzumab (VenG), as established in the randomized CLL14 and CLL13 studies, achieve uMRD <10
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, magrolimab (GS-4721) / Ono Pharma
Trial completion date, Trial primary completion date: Venetoclax With Obinutuzumab and Magrolimab (VENOM) in Relapsed and Refractory Indolent B-cell Malignancies (clinicaltrials.gov) - Jun 18, 2023
P1, N=76, Recruiting,
Trial primary completion date: Dec 2025 --> Aug 2026 Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2025
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Dreyling is still using Rituximab instead of Obinutuzumab??? Kinda shows he's living in the past. Show me where P53 mutated, 17p-, high Ki-67 are doing well on chemo. btw, as for your "vote", please add the number of votes cast so we know that the sample size is relevant. (Twitter) - Jun 16, 2023
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen
Enrollment closed, Trial completion date, Trial primary completion date: Obinutuzumab in Primary FSGS (clinicaltrials.gov) - Jun 15, 2023
P2, N=20, Active, not recruiting,
N=200 --> 300 Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2023 --> Jun 2025
- |||||||||| Journal: First line therapy of CLL. (Pubmed Central) - Jun 13, 2023
When treatment is indicated, several therapeutic options exist today and need to be selected. A combination of the BCL2 inhibitor venetoclax with obinutuzumab, monotherapy with inhibitors of Bruton tyrosine kinase (BTK) such as ibrutinib, acalabrutinib or zanubrutinib, while chemoimmunotherapy (CIT) is disappearing as a therapeutic option.
- |||||||||| Review, Journal: An update on the biologics for the treatment of antiphospholipid syndrome. (Pubmed Central) - Jun 9, 2023
This review focuses on the recent advancements in the pathogenesis of APS and explores the potential of targeted treatments, including eculizumab, rituximab, belimumab, daratumumab, obinutuzumab, and anti-TNF-? antibodies, for APS management.
- |||||||||| ST-067 / Simcha Therap, Keytruda (pembrolizumab) / Merck (MSD), Gazyva (obinutuzumab) / Roche, Biogen
Enrollment change, Combination therapy, Monotherapy, Metastases: KEYNOTE-E64: Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067 (clinicaltrials.gov) - Jun 5, 2023
P1a, N=316, Recruiting,
Even for patients not achieving uMRD (<10), PFS rates remained high with ibrutinib + venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time. N=198 --> 316
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Journal: Noncovalent antibody catenation on a target surface greatly increases the antigen-binding avidity. (Pubmed Central) - Jun 3, 2023
Compared with the mother antibody, Obinutuzumab(Y101L) which targets CD20, the same antibody with fused catenators exhibited significantly enhanced binding to SU-DHL5 cells. Together, the homodimerization-induced antibody catenation would be a new powerful approach to improve antibody applications, including the detection of scarce biomarkers and targeted anticancer therapies.
- |||||||||| MODULE 3: Chronic Lymphocytic Leukemia (CLL) (Hilton Chicago; Grand Ballroom (Level 2)) - May 26, 2023 - Abstract #ASCO2023ASCO_7062;
This activity is supported by educational grants from AbbVie Inc, Genentech, a member of the Roche Group, Genmab US Inc, Karyopharm Therapeutics, Lilly, Regeneron Pharmaceuticals Inc, Sanofi, and Seagen Inc. Clinical, biological and practical factors in the selection of first-line treatment for CLL requiring active therapyLong-term findings from Phase III studies assessing ibrutinib-, acalabrutinib- and zanubrutinib-based therapy for treatment-na
- |||||||||| MODULE 2: Non-Hodgkin and Hodgkin Lymphoma (Hilton Chicago; Grand Ballroom (Level 2)) - May 26, 2023 - Abstract #ASCO2023ASCO_7061;
This activity is supported by educational grants from AbbVie Inc, Genentech, a member of the Roche Group, Genmab US Inc, Karyopharm Therapeutics, Lilly, Regeneron Pharmaceuticals Inc, Sanofi, and Seagen Inc. Key findings from the Phase III POLARIX study comparing polatuzumab vedotin in combination with R-CHP to R-CHOP for untreated diffuse large B-cell lymphoma (DLBCL); recent FDA approval of this regimen and incorporation into clinical practiceAvailable data with and ongoing and planned evaluation of other novel agents for DLBCL in the first-line settingFactors in the selection and sequencing of available treatments for R/R DLBCLPublished research findings with polatuzumab vedotin and bendamustine/rituximab for R/R DLBCLKey clinical trial data with tafasitamab/lenalidomide and loncastuximab tesirine for R/R DLBCLMajor efficacy and safety data with selinexor for patients with R/R DLBCLAvailable results from Phase III studies evaluating CAR T-cell therapy as second-line treatment for DLBCL; FDA approval of axicabtagene ciloleucel and lisocabtagene maraleucel in this settingAvailable data with and ongoing and planned evaluation of novel bispecific antibodies (eg, epcoritamab, glofitamab, mosunetuzumab, odronextamab) targeting CD20 and CD3 in DLBCLIntegration of obinutuzumab into current treatment for follicular lymphoma (FL); final analysis of the Phase III GALLIUM studyLong-term clinical trial findings with lenalidomide/rituximab for treatment-na
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Brukinsa (zanubrutinib) / BeiGene, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Enrollment change: Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) (clinicaltrials.gov) - May 24, 2023
P2, N=230, Recruiting,
Key findings from the Phase III POLARIX study comparing polatuzumab vedotin in combination with R-CHP to R-CHOP for untreated diffuse large B-cell lymphoma (DLBCL); recent FDA approval of this regimen and incorporation into clinical practiceAvailable data with and ongoing and planned evaluation of other novel agents for DLBCL in the first-line settingFactors in the selection and sequencing of available treatments for R/R DLBCLPublished research findings with polatuzumab vedotin and bendamustine/rituximab for R/R DLBCLKey clinical trial data with tafasitamab/lenalidomide and loncastuximab tesirine for R/R DLBCLMajor efficacy and safety data with selinexor for patients with R/R DLBCLAvailable results from Phase III studies evaluating CAR T-cell therapy as second-line treatment for DLBCL; FDA approval of axicabtagene ciloleucel and lisocabtagene maraleucel in this settingAvailable data with and ongoing and planned evaluation of novel bispecific antibodies (eg, epcoritamab, glofitamab, mosunetuzumab, odronextamab) targeting CD20 and CD3 in DLBCLIntegration of obinutuzumab into current treatment for follicular lymphoma (FL); final analysis of the Phase III GALLIUM studyLong-term clinical trial findings with lenalidomide/rituximab for treatment-na N=127 --> 230
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Brukinsa (zanubrutinib) / BeiGene, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Enrollment open, Minimal residual disease: Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab (clinicaltrials.gov) - May 24, 2023
P2, N=50, Recruiting,
N=127 --> 230 Not yet recruiting --> Recruiting
- |||||||||| Trial completion date, Trial primary completion date, FDG PET, Metastases: Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer (clinicaltrials.gov) - May 23, 2023
P1, N=39, Suspended,
Overall, patients with treatment-naive CLL treated with A or A?+?O experienced significant gains in Q-TWiST compared with C?+?O. Trial completion date: May 2023 --> May 2026 | Trial primary completion date: Apr 2023 --> Apr 2025
- |||||||||| CLL Targets Beyond BTKi and Bcl2i (HALL A) - May 20, 2023 - Abstract #ICLLM2023ICLLM_55;
Meanwhile, we have shown that luxeptinib, a dual SYK/BTK kinase inhibitor, has activity in BTK inhibitor-resistant lymphoid models in vitro.5 Luxeptinib is now being investigated in lcinical trials in hematologic malignancies...The early results of MS-553, a selective PKC-? inhibitor, indicates that this agent is tolerable and effective both as single agent and in combination with venetoclax.8 Proteolysis-targeting chimeras (PROTACs) are a new class of small molecules with two covalently-linked ligands recruiting target protein and E3 ubiquitin ligase together to trigger and enable proteasomal degradation of the target protein.9
- |||||||||| Columvi (glofitamab-gxbm) / Roche, Rituxan (rituximab) / Roche
Trial completion date, Trial primary completion date, Combination therapy: GO43693: A Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Participants With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell Lymphoma (clinicaltrials.gov) - May 19, 2023
P1, N=40, Recruiting,
inhibitor, indicates that this agent is tolerable and effective both as single agent and in combination with venetoclax.8 Proteolysis-targeting chimeras (PROTACs) are a new class of small molecules with two covalently-linked ligands recruiting target protein and E3 ubiquitin ligase together to trigger and enable proteasomal degradation of the target protein.9 Trial completion date: Oct 2024 --> Jun 2024 | Trial primary completion date: Jul 2023 --> Jun 2024
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Rituxan (rituximab) / Roche
Enrollment open: CRISTALLO: A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/ Bendamustine And Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL (17P) or TP53 Mutation (clinicaltrials.gov) - May 17, 2023
P3, N=165, Recruiting,
Trial completion date: Oct 2024 --> Jun 2024 | Trial primary completion date: Jul 2023 --> Jun 2024 Active, not recruiting --> Recruiting
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Columvi (glofitamab-gxbm) / Roche, Gazyva (obinutuzumab) / Roche, Biogen
New P1/2 trial: NCI-2023-03181: Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma (clinicaltrials.gov) - May 16, 2023
P1/2, N=50, Not yet recruiting,
- |||||||||| Journal, HEOR, IO biomarker, Cost-effectiveness, Cost effectiveness: Cost-effectiveness of targeted treatment vs chemoimmunotherapy in treatment-na (Pubmed Central) - May 15, 2023
Trial completion date: Nov 2029 --> Apr 2029 | Trial primary completion date: Nov 2029 --> Apr 2029 Several targeted treatments, such as venetoclax + obinutuzumab (VenO) and ibrutinib, have emerged to treat treatment-na
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
Journal: First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. (Pubmed Central) - May 14, 2023
P3
Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA-CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.).
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