Podcasts about idelalisib

In this episode, Julie M. Vose, MD, MBA;  Brad S. Kahl, MD; and  John P. Leonard, MD, discuss treatment approaches for patients with B-cell lymphomas, including information on: Follicular lymphomaMarginal zone lymphomaMantle cell lymphomaDiffuse large B-cell lymphomaPosttransplant lymphoproliferative disorderPresenters:Julie M. Vose, MD, MBAChief, Division of Oncology and HematologyNeumann M. and Mildred E. Harris ProfessorDepartment of Internal MedicineUniversity of Nebraska Medical CenterOmaha, NebraskaBrad S. Kahl, MDProfessor of MedicineDepartment of Medical OncologyWashington University School of MedicineSt Louis, MissouriJohn P. Leonard, MDRichard T. Silver Distinguished Professor of Hematology and Medical OncologyProfessor of MedicineWeill Cornell MedicineNew York Presbyterian HospitalNew York, New YorkLink to the complete program, including downloadable slidesets, expert commentaries, an on-demand webcast, and treatment resource guides:https://bit.ly/3tb47wU

In this episode, Jennifer R. Brown, MD, PhD, and John Allan, MD, discuss recent key clinical trial results in CLL presented at the 2020 annual meetings of the American Society of Clinical Oncology (ASCO) and the European Hematology Association (EHA). Studies and topics include:ASCEND: acalabrutinib vs idelalisib plus rituximab or BRACE-CL-001: acalabrutinib long-term efficacyCLL14: Venetoclax plus obinutuzumabCLARITY: Ibrutinib plus venetoclaxMeasurable residual disease (MRD)Complex karyotypesZanubrutinib plus obinutuzumab and venetoclaxPresenters:Jennifer R. Brown, MD, PhDAssociate Professor of MedicineDepartment of Hematologic MalignanciesDana-Farber Cancer InstituteHarvard Medical SchoolDirector, CLL CenterDepartment of Medical OncologyDana-Farber Cancer InstituteBoston, MassachusettsJohn Allan, MDAssistant Professor of MedicineDivision of Hematology and Medical OncologyWeill Cornell MedicineNew York, New YorkContent based on an online CME program supported by an educational grant from AstraZeneca.Link to full program: https://bit.ly/3aSfekM

Dr. Ian Flinn, Medical Oncologist specializing in hematologic malignancies at Tennessee Oncology, discusses the recent FDA approval of duvelisib for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT (Intro Music Playing) As a background to today's discussion, the PI3K are a family of lipid kinases that sit at the crossroads of numerous signaling events that drive many malignancies, including certain lymphomas, and chronic lymphocytic leukemia. There are four isoforms of the PI3K-- alpha, beta, delta, and gamma. Isoform specific inhibitors are attractive because they may lead to efficacy without the toxicity of pan inhibitors. Idelalisib, which is a delta isoform inhibitor, was the first PI3K inhibitor be approved for lymphoma in CLL. The delta isoform is a particular interest in B cell malignancies because its expression is normally restricted to cells of a hematopoietic origin. In data from gene knockout models, show that it has a key role in B cell signaling, development, and survival. Selective targeting of the delta isoform should not alter insulin signaling, which is mediated by the ubiquitously expressed alpha isoform. However, narrow targeting could lead to mechanisms of resistance to upregulation of other isoforms. This has been demonstrated in mantle cell lymphoma where the alpha isoform is expressed in relapse patients. Duvelisib is a dual inhibitor of both the delta and gamma isoforms of the PI3K. Inhibiting the gamma isoform may be important because of its inhibitory effect, not only in the malignant cell, but also in the micro-environment, which provides important survival signals to malignant cells. Both idelalisib and copanlisib, an inhibitor of the delta and alpha isoforms, are currently FDA approved for third line follicular cell lymphoma. And idelalisib is approved in combination with rituximab in relapse CLL. On September 24, 2018, the Food and Drug Administration granted approval for duvelisib for patients with relapsed refractory chronic lyphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma after at least two prior therapies. The approval of duvelisib in CLL was based on the DUO trial, a large international randomized phase III trial comparing duvelisib, at 25 milligrams orally, twice daily, to ofatumumab, given according to the package label. The results of the duo trial have been published in Blood. In a subset analysis of 196 patients receiving at least two prior therapies, the median progression pre-survival was 16.4 months in the duvelisib arm, and 9.1 months in the ofatumumab arm, with a hazard ratio of 0.40. The overall response rate of 78% with duvelisib was twice the 39% seen with ofatumumab. The follicular lymphoma indication is based on the Dynamo trial, a single arm multi-center trial of duvelisib, which enrolled 83 patients with follicular lymphoma who are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The overall response rate, determined by an independent response committee, was 42%. Of the 35 responding patients, 15, or 43%, maintained responses for at least six months. And 6, or 17%, maintained responses for at least 12 months. The most common adverse reactions with an instance of greater than or equal to 20% were diarrhea, or colitis, neutropenium, rash, fatigue, pyrexia, cough, nausea, upper respiratory tract infection, pneumonia, muscle skeletal pain, and anemia. Over the last decade, we've seen substantial advances in the treatment of low grade lymphoma and CLL, especially in the front-line setting. Unfortunately for patients with relapse and refractory disease, new agents are needed. The approval of duvelisib is an important addition to our armamentarium for these patients. And we'll have an immediate impact. However, to have its greatest effect, strategies will need to be devised to move this drug earlier in the natural history of these diseases. Such approaches might include alternative dosing and scheduling, as well as combination regiments. Duvelisib is a novel PI3K inhibitor and is differentiated from other PI3K inhibitors, because it targets both the delta and gamma isoforms. Consequently, it is being studied in a broader array of diseases, including T cell malignancies, where promising activity has been seen. (Outro Music Playing) Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on drug approvals visit the comprehensive e-learning center at university.asco.org.

Dr Zelenetz talks to ecancertv at ASH 2015 about results of a phase III randomised, double-blind, placebo-controlled study that investigated whether adding idelalisib to standard treatment for relapsed or refractory chronic lymphocytic leukaemia (CLL) would be better than the standard treatment alone. Idelalisib is a first-in-class oral inhibitor or PI3k delta that is approved for use in combination with rituximab for the treatment of patients with relapsed CLL. It is also approved as first-line treatment for CLL patients with the 17p deletion or TP53 mutation who are not suitable for chemo-immunotherapy. The phase III trial included 416 patients who were randomized to receive the standard regimen of bendamustine plus rituximab with or without idelalisib. Results showed a significantly longer progression-free survival with the addition of idelalisib (23 vs 11 months).

Dr Zelenetz presents, at a press conference at ASH 2015, results of a phase III randomised double-blind placebo-controlled study. Idelalisib plus bendamustine and rituximab is superior to rituximab alone in patients with relapsed/refractory chronic lymphocytic leukaemia.

Dr George Follows (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK) talks with Dr Andrew Zelenetz (Memorial Sloan Kettering Cancer Centre, New York, USA) at the BSH 2016 conference in Glasgow. Dr Zelenetz was presenting in Glasgow with a late breaking poster detailing the outcomes of a trial to treat relapsed chronic lymphocytic leukaemia with a combination of idelalisib, bendamustine and rituximab The results of the trial report overwhelming efficacy of the combination compared to placebo or bendamustine with rituximab. Dr Follows and Dr Zelenetz discuss the impact of these results, considering risks such as infection, and the value of the combined IBR arm of the trial against BR alone, or the as-yet-unreported IR arm.

Prof Stilgenbauer (University of Ulm, Ulm, Germany) chairs an expert discussion for ecancertv on the latest data presented at ASH 2016 helping to shape the rapidly evolving CLL landscape. He is joined by Dr Jones (Ohio State University, Columbus, USA), Prof Wendtner (Klinikum Schwabing, Munich, Germany) and Prof Coutre (Stanford University School of Medicine, Stanford, USA). The panel first looked at presentations focused on Lenalidomide (LEN) in the maintenance setting, with results of the M1 trial of the German CLL study group showing LEN substantially prolonged PFS in high risk CLL patients as a maintenance option after chemoimmunotherapy. Although positive results were seen, it was suggested that question marks remain over the clinical utility of this treatment option. At ‘the forefront of chemo free treatments’ is ibrutinib, with follow-up data discussed from the Phase III RESONATE-2 trial, which led to the approval of ibrutinib as a first-line treatment for patients with CLL earlier in the year. Following this, the panel discussed efficacy and safety results from the longest follow-up to date for ibrutinib treated CLL/SLL patients, showing durable responses through five years of treatment. There were also positive results seen with Idelalisib in combination with Bendamustine and Rituximab in patients with Relapsed/Refractory CLL. Following previous reports of improved PFS, data presented at this year’s ASH also showed OS improvement across risk categories. Discussion then moved on to data looking at novel agents and combinations including venetoclax (VEN) monotherapy and in combination with obinutuzmab and ibrutinib. The panel also touched on results from the Phase II CLL2-BIG trial of Bendamustine followed by GA101 and Ibrutinib followed by Ibrutinib and GA101 maintenance in CLL patients. With the recent paradigm shifts in how CLL is treated, the introduction of novel agents and combinations seek to further ‘expand the CLL toolbox’. With the immunotherapy ‘hype not over’ and the role of CAR T-cell therapies being further explored, advances in CLL are set to remain the pacemaker in haematology.

Dr Furman talks to ecancertv at ASH 2013 about his study: "A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib and Rituximab for Previously Treated Patients with Chronic Lymphocytic Leukemia (CLL)" Idelalisib (IDELA) is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues. This Phase 3 study evaluated the efficacy and safety of Idelalisib plus rituximab vs placebo plus retuximab in patients with previously treated CLL. Idelalisib plus rituximab demonstrated statistically significant improvement with acceptable safety over placebo plus rituximab in PFS, ORR, LNR and OS in heavily pretreated patients with relapsed CLL, including those with adverse genetic features.