- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
A Phase II Trial of the Combination of Obinutuzumab, Venetoclax, and Ibrutinib in Patients with Previously Untreated Follicular Lymphoma () - Nov 29, 2022 - Abstract #ASH2022ASH_7385;
The other 5 patients remain on treatment.Conclusion : Although the sample size and duration of follow-up were limited, the combination of obinutuzumab, venetoclax, and ibrutinib demonstrated remarkable efficacy and is a promising non-chemotherapeutic alternative for untreated FL. Non-hematologic toxicities were manageable, and no hematologic toxicity led to clinical complications.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Obinutuzumab Versus Rituximab Based First-Line Chemoimmunotherapy for Follicular Lymphoma - a Real-World Multicenter Retrospective Cohort Study () - Nov 29, 2022 - Abstract #ASH2022ASH_7382;
Overall, no statistically significant difference was evident in adverse events of grades 3 to 5 (hematological and non-hematological) between R and G-based treatments (76.9% vs. 82%, p=0.427) nor in complete remission rates at the end of induction therapy (79.5% vs. 84.6%, p=0.147).Baseline factors significantly associated with any infection in univariate analysis included female gender, chronic obstructive pulmonary disease, use of GCSF prophylaxis, elevated LDH, beta2 microglobulin and lower levels of hemoglobin before `treatment commencement. None of the parameters was found to be significantly associated with any infection in multivariable analysis, albeit gender and LDH values had a trend towards significance.Conclusion s - In this first and largest real-life study of first line treated patients with follicular lymphoma, we did not observe excess toxicity with G- compared to R- based therapy during the induction and 6 months post induction period.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Obinutuzumab Induced ITP:a Case Report () - Nov 29, 2022 - Abstract #ASH2022ASH_7371;
She was then treated with second-line therapy with Polatuzumab and Bendamustine along with rituximab for cycles after which the bendamustine was removed for the final 6 cycles to ensure she was a candidate for Car-T therapy...Treatment has been started for ITP and patient has been started on Prednisone 1mg/kg on daily basis and IVIG 1g/kg for doses...In such, we used IVIG and glucocorticoid therapy to halt platelet destruction and assist platelet count stabilization and recovery. This case highlights the benefit of ITP like therapies and thus raises the possibility that the acute thrombocytopenia within the first 24 hours after administration of obinatuzumab may be immune mediated.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Journal, Real-world evidence: Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario. (Pubmed Central) - Nov 27, 2022
Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Journal: Efficacy and Safety of Obinutuzumab-chemotherapy Combinations in Front-line Treatment of Follicular Non-Hodgkin Lymphoma During the COVID-19 Pandemic: A Study of KROHEM, the Croatian Cooperative Group for Hematologic Diseases. (Pubmed Central) - Nov 22, 2022
In multivariate analysis, G-B in comparison to G-CHOP was an independent prognostic factor (P = 0.044, hazard ratio = 9.81) after adjustment for age, sex and Follicular Lymphoma International Prognostic Index (FLIPI). Based on our experience G has excellent antilymphoma activity in patients receiving front-line treatment for FL in real-life setting, but during the COVID-19 pandemic, it should be preferentially combined with CHOP, at least in patients younger than 65.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Retrospective data, Journal: A Novel approach using O-CVP to treat paraneoplastic NMO spectrum disorder associated with follicular lymphoma. (Pubmed Central) - Nov 22, 2022
Following two cycles, there was almost complete radiological remission of the myelitis and the patient showed some improvement in her neurological function. This case illustrates the heterogeneous aetiology that LETM may have and that O-CVP may be used as therapeutic option in patients with NMOSD driven by follicular lymphoma.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Imbruvica (ibrutinib) / AbbVie, J&J
Trial primary completion date, Combination therapy: Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or Previously Untreated Chronic Lymphocytic Leukemia (clinicaltrials.gov) - Nov 17, 2022
P1/2, N=87, Active, not recruiting,
Further research is required to develop validated prognostic indices for HT risk and guide treatment decisions. Trial primary completion date: Aug 2022 --> Aug 2023
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Journal: Chicken-derived CD20 antibodies with potent B-cell depletion activity. (Pubmed Central) - Nov 15, 2022
The chicken-human chimaeric antibodies exhibit at least 10-fold enhanced antibody-dependent cellular cytotoxicity (ADCC) and 4-8-fold stronger complement-dependent cytotoxicity (CDC) relative to the clinically used mouse-human chimaeric anti-hCD20 antibody rituximab (RTX)...A humanized version of one antibody, hAC11-10, was created by complementarity-determining region (CDR) grafting into a human variable region framework and this molecule retained the ADCC, in vitro human whole-blood B-cell depletion, and in vivo lymphoma cell depletion activities of the parent. These mAbs represent promising monotherapy candidates for improving upon current less-than-ideal clinical outcomes in lymphoid malignancies and provide an arsenal of biologically relevant molecules for the development of next-generation CD20-mediated immunotherapies including bispecific T-cell engagers (BiTE), antibody-drug conjugates (ADC) and chimaeric antigen receptor-engineered T (CAR-T) cells.
- |||||||||| Journal, IO biomarker: Novel and emerging treatment strategies for lupus nephritis. (Pubmed Central) - Nov 15, 2022
Inhibition of B-cell activating factor by belimumab confers superior renal response when added to the standard of care (SOC) regimens, leading to its recent approval for LN...A newer generation calcineurin inhibitor, voclosporin, when combined with SOC, results in better renal responses in LN...While these novel agents improve the short-term renal responses without increased toxicities, long-term data on disease progression and safety remain to be established. Patient stratification by clinical phenotypes, biomarkers and molecular profiles helps enhance the efficacy and cost-effectiveness of novel therapies of LN.
- |||||||||| Journal, IO biomarker: Immunotherapy combinations for chronic lymphocytic leukemia: Advantages and disadvantages. (Pubmed Central) - Nov 15, 2022
Rituximab and obinutuzumab have been combined with chemotherapy, and more recently, with BTK inhibitors, PI3K inhibitors and venetoclax...Venetoclax is typically combined with anti-CD20 Mabs in CLL. Generally, the optimal sequencing of therapies remains to be established, and the selection of upfront therapy needs to be tailored to the individual patient.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
P1/2 data, Journal: A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL. (Pubmed Central) - Nov 15, 2022
P1/2
LO-CHOP demonstrates high efficacy and tolerability in newly diagnosed DLBCL, leading to a high rate of undetectable minimal residual disease by ctDNA by end of therapy. This trial is registered at www.clinicaltrials.gov as NCT02529852.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
Enrollment closed, Combination therapy, Minimal residual disease: A Study on Limiting Treatment Time With Acalabrutinib Combined With Obinutuzumab in People With CLL or SLL (clinicaltrials.gov) - Nov 14, 2022
P2, N=55, Active, not recruiting,
This trial is registered at www.clinicaltrials.gov as NCT02529852. Recruiting --> Active, not recruiting
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, litifilimab (BIIB059) / Biogen, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Review, CAR T-Cell Therapy: Year in review by Carol Langford at #ACR22: IVIg in #dermatomyositis, CAR T cells against CD19, litifilimab, obinutuzumab, iberomide in #SLE, tocilizumab in #PMR (Twitter) - Nov 12, 2022
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
Trial completion date, Trial primary completion date: CLL2-BAAG: Sequential Regimen of Bendamustin-Debulking Followed by Obinutuzumab, Acalabrutinib and Venetoclax in Patients With Relapsed/Refractory CLL (clinicaltrials.gov) - Nov 9, 2022
P2, N=46, Active, not recruiting,
Trial primary completion date: Nov 2022 --> Apr 2025 Trial completion date: Nov 2024 --> Aug 2023 | Trial primary completion date: May 2023 --> Dec 2022
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Brukinsa (zanubrutinib) / BeiGene, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Enrollment closed, Trial completion date, Trial primary completion date: CLL2-BZAG: Sequential Regimen of Bendamustine Followed by Obinutuzumab (GA101), Zanubrutinib (BGB-3111) and Venetoclax (ABT-199) in Patients With Relapsed/Refractory CLL (clinicaltrials.gov) - Nov 9, 2022
P2, N=42, Active, not recruiting,
Trial completion date: Nov 2024 --> Aug 2023 | Trial primary completion date: May 2023 --> Dec 2022 Recruiting --> Active, not recruiting | Trial completion date: Sep 2025 --> Mar 2027 | Trial primary completion date: Oct 2022 --> Apr 2025
- |||||||||| Clinical, Journal: B cell depletion and inhibition in systemic lupus erythematosus. (Pubmed Central) - Nov 8, 2022
However, after more than two decades of research and over 40 randomized clinical trials, only one such therapy, belimumab, has been approved for use in SLE...Despite a lack of supporting phase III evidence, rituximab is used off-label in SLE...Successful phase II trials have recently been reported for obinutuzumab and telitacicept with larger confirmatory trials currently underway. Refinements in pharmaceutical mechanisms of action, trial design, and patient selection have resulted in recent preliminary successes, offering renewed optimism for B-cell targeted therapeutics in SLE management.
- |||||||||| Enrollment open, Combination therapy: NP40126: A Study of Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Non-Hodgkin Lymphomas or With DLBCL (clinicaltrials.gov) - Nov 7, 2022
P1, N=172, Recruiting,
Trial completion date: Apr 2028 --> Nov 2027 Active, not recruiting --> Recruiting
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen
Enrollment closed, Trial primary completion date: OLYMP-1: Obinutuzumab in Marginal Zone Lymphoma (clinicaltrials.gov) - Nov 7, 2022
P2, N=56, Active, not recruiting,
Active, not recruiting --> Recruiting Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2022 --> Jun 2023
- |||||||||| Review, Journal: How Have Targeted Agents Changed the Treatment Landscape for Elderly Patients with CLL? (Pubmed Central) - Nov 6, 2022
Treatment of elderly patients with CLL should be made on a case-by-case basis based on a patient's fitness, comorbid medical conditions, and concomitant medications. The use of targeted agents has improved outcomes in this patient population, but further studies are needed to determine the best practice.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Longitudinal Profiling of the T Cell Compartment in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_6264;
In conclusion, ven treatment led to increased numbers of CD8+ effector subpopulations along with prominent clonal expansions and transcriptional rewiring that could conceivably contribute to clinical response. Downregulation of immune-related genes implicated in core regulatory/activation pathways supports immune recovery by ven, offering a rationale for future combination strategies aiming to increase the depth of clinical response.
- |||||||||| Arzerra (ofatumumab) / Novartis, Genmab
Early Treatment with Ofatumumab in Patients with High-Risk CLL (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_6259;
The PFS was similar to that of similarly designed trials with rituximab monotherapy and rituximab in combination with alemtuzumab, respectively. Further internal matched analysis is being conducted to compare time to second treatment.
- |||||||||| Calquence (acalabrutinib) / AstraZeneca
Changes in the T Helper Cell Compartment during Treatment with the BTK Inhibitor Acalabrutinib (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_6250;
P2
Collectively, the reduction in T cells and T helper cell subset numbers, along with changes in surface activation markers, and reduced cytokine and Ki-67 expression suggest that an activated pre-treatment T helper cell compartment normalizes during continuous acalabrutinib therapy. These findings are reminiscent of the T cell data from patients receiving ibrutinib therapy, suggesting that off-target effects of the BTK inhibitor may not dictate T helper cell changes, and these may rather be due to activation by the CLL clone, which diminishes as the underlying disease responds to treatment.
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