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Meet The ProfessorManagement of Chronic Lymphocytic LeukemiaWilliam G Wierda, MD, PhDDB Lane Cancer Research Distinguished ProfessorDepartment of LeukemiaDivision of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHouston, Texas
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Dr Love — DisclosuresDr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educationalgrants to develop CME activities from the following commercial interests: AbbVie Inc, Acerta Pharma — A memberof the AstraZeneca Group, Adaptive Biotechnologies Corporation, Agendia Inc, Agios Pharmaceuticals Inc, AmgenInc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCarePharmaceuticals, Biodesix Inc, bioTheranostics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc,Bristol-Myers Squibb Company, Celgene Corporation, Clovis Oncology, Daiichi Sankyo Inc, Dendreon PharmaceuticalsInc, Eisai Inc, EMD Serono Inc, Exelixis Inc, Foundation Medicine, Genentech, a member of the Roche Group,Genmab, Genomic Health Inc, Gilead Sciences Inc, GlaxoSmithKline, Grail Inc, Guardant Health, Halozyme Inc,Helsinn Healthcare SA, ImmunoGen Inc, Incyte Corporation, Infinity Pharmaceuticals Inc, Ipsen BiopharmaceuticalsInc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Kite, A GileadCompany, Lexicon Pharmaceuticals Inc, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company,Merck, Merrimack Pharmaceuticals Inc, Myriad Genetic Laboratories Inc, Natera Inc, Novartis, Oncopeptides, PfizerInc, Pharmacyclics LLC, an AbbVie Company, Prometheus Laboratories Inc, Puma Biotechnology Inc, RegeneronPharmaceuticals Inc, Sandoz Inc, a Novartis Division, Sanofi Genzyme, Seattle Genetics, Sirtex Medical Ltd, SpectrumPharmaceuticals Inc, Sumitomo Dainippon Pharma Oncology Inc, Taiho Oncology Inc, Takeda Oncology, Tesaro, AGSK Company, Teva Oncology, Tokai Pharmaceuticals Inc and Verastem Inc.
Research To Practice CME Planning Committee Members,Staff and ReviewersPlanners, scientific staff and independent reviewers for Research To Practicehave no relevant conflicts of interest to disclose.
Dr Wierda — DisclosuresNo financial interests or affiliations to disclose
We Encourage Clinicians in Practice to Submit QuestionsFeel free to submit questions now before the programbegins and throughout the program.
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Upcoming Live WebinarsMonday, October 5, 202012:00 PM – 1:00 PM ETWednesday, October 7, 202012:00 PM – 1:00 PM ETMeet The Professor:Management of Lung CancerMeet The Professor: Managementof Chronic LymphocyticLeukemiaFacultyProfessor Tony SK Mok, MDModeratorNeil Love, MDFacultyMitchell R Smith, MD, PhDModeratorNeil Love, MD
Upcoming Live WebinarsThursday, October 8, 202012:00 PM – 1:00 PM ETMeet The Professor:Immunotherapy and NovelAgents in Gynecologic CancersFacultyBrian M Slomovitz, MDModeratorNeil Love, MD
Thank you for joining us!CME and MOC credit information will be emailed toeach participant within 5 days.
Meet The ProfessorManagement of Chronic Lymphocytic LeukemiaWilliam G Wierda, MD, PhDDB Lane Cancer Research Distinguished ProfessorDepartment of LeukemiaDivision of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHouston, Texas
Meet The Professor Program Participating FacultyMatthew S Davids, MD, MMScAssociate Professor of MedicineHarvard Medical SchoolDirector of Clinical ResearchDivision of LymphomaDana-Farber Cancer InstituteBoston, MassachusettsBrian T Hill, MD, PhDDirector, Lymphoid Malignancy ProgramCleveland Clinic Taussig Cancer InstituteCleveland, OhioIan W Flinn, MD, PhDDirector of Lymphoma Research ProgramSarah Cannon Research InstituteTennessee OncologyNashville, TennesseeBrad S Kahl, MDProfessor of MedicineWashington University School of MedicineDirector, Lymphoma ProgramSiteman Cancer CenterSt Louis, Missouri
Meet The Professor Program Participating FacultyAnthony R Mato, MD, MSCEAssociate AttendingDirector, Chronic Lymphocytic LeukemiaProgramMemorial Sloan Kettering Cancer CenterNew York, New YorkKerry Rogers, MDAssistant Professor in the Division of HematologyThe Ohio State UniversityColumbus, OhioJohn M Pagel, MD, PhDChief of Hematologic MalignanciesCenter for Blood Disorders and StemCell TransplantationSwedish Cancer InstituteSeattle, WashingtonJeff Sharman, MDWillamette Valley Cancer Institute andResearch CenterMedical Director of Hematology ResearchUS OncologyEugene, Oregon
Meet The Professor Program Participating FacultyMitchell R Smith, MD, PhDProfessor of MedicineAssociate Center Director for ClinicalInvestigationsDirector, Division of Hematology and OncologyGW Cancer CenterWashington, DCWilliam G Wierda, MD, PhDDB Lane Cancer ResearchDistinguished ProfessorDepartment of LeukemiaDivision of Cancer MedicineThe University of TexasMD Anderson Cancer CenterHouston, TexasJennifer Woyach, MDProfessorDivision of HematologyDepartment of Internal MedicineThe Ohio State UniversityComprehensive Cancer CenterColumbus, OhioProject ChairNeil Love, MDResearch To PracticeMiami, Florida
We Encourage Clinicians in Practice to Submit QuestionsYou may submit questionsusing the Zoom Chatoption belowFeel free to submit questions now before theprogram begins and throughout the program.
Familiarizing Yourself with the Zoom InterfaceHow to answer poll questionsWhen a poll question pops up, click your answer choice from the availableoptions. Results will be shown after everyone has answered.
Meet The ProfessorManagement of Lung CancerMonday, October 5, 202012:00 PM – 1:00 PM ETFacultyProfessor Tony SK Mok, MDModeratorNeil Love, MD
Meet The ProfessorManagement of Chronic Lymphocytic LeukemiaWednesday, October 7, 202012:00 PM – 1:00 PM ETFacultyMitchell R Smith, MD, PhDModeratorNeil Love, MD
Meet The ProfessorImmunotherapy and Novel Agentsin Gynecologic CancersThursday, October 8, 202012:00 PM – 1:00 PM ETFacultyBrian M Slomovitz, MDModeratorNeil Love, MD
Meet The ProfessorManagement of Chronic Lymphocytic LeukemiaWilliam G Wierda, MD, PhDDB Lane Cancer Research Distinguished ProfessorDepartment of LeukemiaDivision of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHouston, Texas
Zanetta S Lamar, MDFlorida Cancer Specialists and Research InstituteNaples, FloridaNeil Morganstein, MDHematology OncologyAtlantic Health SystemSummit, New JerseyErik J Rupard, MDChief, Section of Hematology-OncologyMcGlinn Cancer InstituteReading Hospital and Medical CenterWest Reading, Pennsylvania
Blood 2020;135(17):1421-27
Selecting First-Line CLL TreatmentSelecting Treatment forRelapsed/Refractory CLLWierda Blood 2020
Lancet Haematol 2020;7(2):e168-76
Meet The Professor with Dr WierdaMODULE 1: Cases from the Community (Drs Lamar, Morganstein and Rupard) Dr Lamar: An asymptomatic 81-year-old man with newly diagnosed CLLQuestions and Comments: First-line treatment of CLLQuestions and Comments: Relevance of TP53 mutation testing in CLL prognosticationQuestions and Comments: First-line therapy for older patients with comorbiditiesQuestions and Comments: Current role of up-front chemotherapyDr Rupard: A 94-year-old man with CLL and Merkel cell carcinomaMODULE 2: CLL Journal Club with Dr WierdaMODULE 3: Beyond the Guidelines – Clinical Investigator Approaches to Common Clinical ScenariosMODULE 4: Key Recent Data Sets
Case Presentation – Dr Lamar: An asymptomatic81-year-old man with newly diagnosed CLL December 2019: Presents with elevated white blood cell countfound on routine blood workDr Zanetta Lamar Flow cytometry: CD5 , CD23 , CD38-, ZAP70-, IGHV mutated FISH: del17p negative CT scan shows splenomegaly, 17 cm Observation recommended; atient obtained second opinion at academic center thatrecommended treatment with obinutuzumab/venetoclaxQuestions Do you routinely use asymptomatic splenomegaly or nodal enlargement alone astreatment indications? If so, do you have any data? Could you expound on why this waschanged in the most recent guidelines update? Do you incorporate MRD testing in your management of patients with CLL?
Blood 2019;131(25):2745-60
Questions and Comments: First-line treatment of CLLDr Zanetta Lamar
Questions and Comments: Relevance of TP53 mutation testing inCLL prognosticationDr Neil Morganstein
Questions and Comments: First-line therapy for older patientswith comorbiditiesDr Neil Morganstein
Questions and Comments: Current role of up-front chemotherapyDr Neil Morganstein
Case Presentation – Dr Rupard: A 94-year-old manwith CLL and Merkel cell carcinoma Active farmer presents in emergency department with a “scalp lesion” White blood cell count: 84,000- 90% lymphocytes- No anemia or thrombocytopenia Lymph node positive Biopsy of scalp lesion: Merkel cell carcinoma Did not require treatment for CLLQuestions How often do you see Merkel cell carcinoma in patients with CLL? How often do yousee other skin tumors in patients with CLL?Dr Eric Rupard
Meet The Professor with Dr WierdaMODULE 1: Cases from the Community (Drs Lamar, Morganstein and Rupard)MODULE 2: CLL Journal Club with Dr Wierda Management of leukemia in the era of COVID-19Adverse events associated with novel therapies for hematologic cancersMature results from a Phase II study of acalabrutinib for treatment-naïve CLLFungal infections in patients with CLL receiving ibrutinibRichter’s transformation in patients with CLL during interruption of ibrutinib treatmentClinical significance and predictive factors associated with achieving complete remission with ibrutinibMechanistic model of minimal residual disease (MRD) kinetics with venetoclaxCAPTIVATE trial: Ibrutinib with venetoclax as first-line therapy for CLL in MRD cohortIbrutinib with venetoclax in high-risk CLLCAR T-cell therapy for CD19-positive lymphoid tumorsMODULE 3: Beyond the Guidelines – Clinical Investigator Approaches to Common Clinical ScenariosMODULE 4: Key Recent Data Sets
Acta Haematol 2020;11:1-13
Ann Emerg Med 2020;75(2):264-86
Shah Ann Emerg Med 2020
Acalabrutinib in Treatment-Naïve ChronicLymphocytic Leukemia: Mature Results fromPhase II Study Demonstrating DurableRemissions and Long-Term TolerabilityByrd JC et al.ASCO 2020;Abstract 8024.
Leuk Lymphoma 2020;61(10):2488-91
Blood Adv 2020;4(18):4508-11
Blood 2020;135(7):510-13
Response Rate Over Time with IbrutinibStrati Blood 2020
Clin Pharmacol Ther 2020;[Online ahead of print]
Integrated Mechanistic MRD ModelGopalakrishnan Clin Pharmacol Ther 2020
Gopalakrishnan Clin Pharmacol Ther 2020
Ibrutinib (Ibr) plus Venetoclax (Ven) for First-LineTreatment of Chronic Lymphocytic Leukemia(CLL)/Small Lymphocytic Lymphoma (SLL): Resultsfrom the MRD Cohort of the Phase 2 CAPTIVATE StudyTam CS et al.ASH 2019;Abstract 35.
Venetoclax Added to Ibrutinib in High-Risk CLLAchieves a High Rate of Undetectable MinimalResidual DiseaseThompson PA et al.ASH 2019;Abstract 358.
N Engl J Med 2020;382(6):545-53
Meet The Professor with Dr WierdaMODULE 1: Cases from the Community (Drs Lamar, Morganstein and Rupard)MODULE 2: CLL Journal Club with Dr WierdaMODULE 3: Beyond the Guidelines – Clinical Investigator Approaches to Common Clinical ScenariosMODULE 4: Key Recent Data Sets PFS and rate and duration of MRD negativity with venetoclax/obinutuzumab (CLL14 trial)Acalabrutinib for previously untreated CLL (ELEVATE-TN trial)Extended follow-up results with ibrutinib/rituximab in younger patients (ECOG-E1912 trial)CAPTIVATE MRD cohort: Efficacy and safety results with ibrutinib lead-in and ibrutinib/venetoclaxcombination
What is your usual preferred initial regimen for a 60-year-oldpatient with CLL with IGHV mutation but no del(17p) or TP53mutation who requires treatment?1. FCR2. Ibrutinib3. Ibrutinib rituximab4. Ibrutinib obinutuzumab5. Acalabrutinib6. Acalabrutinib obinutuzumab7. Venetoclax obinutuzumab8. Other
What is your usual preferred initial regimen for a 60-year-oldpatient with CLL with IGHV mutation but no del(17p) or TP53mutation who requires treatment?Venetoclax obinutuzumabIbrutinib or FCRVenetoclax obinutuzumabFCRVenetoclax obinutuzumabor BRFCRVenetoclax obinutuzumabFCRFCRVenetoclax obinutuzumabAcalabrutinibBR bendamustine/rituximab; FCR fludarabine/cyclosphosphamide/rituximab (FCR)
What is your usual preferred initial regimen for a 75-year-oldpatient with CLL with IGHV mutation but no del(17p) or TP53mutation who requires treatment?Venetoclax obinutuzumabAcalabrutinib or venetoclax obinutuzumabAcalabrutinibVenetoclax obinutuzumabObinutuzumabIbrutinibVenetoclax obinutuzumabVenetoclax obinutuzumabAcalabrutinibIbrutinibAcalabrutinib
What is your usual preferred initial regimen for a 60-year-oldpatient with CLL with unmutated IGHV and no del(17p) or TP53mutation who requires treatment?1. FCR2. Ibrutinib3. Ibrutinib rituximab4. Ibrutinib obinutuzumab5. Acalabrutinib6. Acalabrutinib obinutuzumab7. Venetoclax obinutuzumab8. Other
What is your usual preferred initial regimen for a 60-year-oldpatient with CLL with unmutated IGHV and no del(17p) or TP53mutation who requires treatment?Venetoclax obinutuzumabAcalabrutinib or venetoclax obinutuzumabVenetoclax obinutuzumabAcalabrutinibVenetoclax obinutuzumabVenetoclax obinutuzumabVenetoclax obinutuzumabVenetoclax obinutuzumabVenetoclax obinutuzumabIbrutinibAcalabrutinib
What is your usual preferred initial regimen for a 75-year-oldpatient with CLL with unmutated IGHV and no del(17p) or TP53mutation who requires treatment?Venetoclax obinutuzumabAcalabrutinib or venetoclax obinutuzumabAcalabrutinibAcalabrutinibVenetoclax obinutuzumabIbrutinibVenetoclax labrutinib
What is your usual preferred initial regimen for a 75-year-oldpatient with CLL with unmutated IGHV and no del(17p) or TP53mutation who requires treatment and has bulky disease?Venetoclax bVenetoclax obinutuzumabVenetoclax obinutuzumabVenetoclax obinutuzumabAcalabrutinibAcalabrutinib obinutuzumabIbrutinibAcalabrutinib
What is your usual preferred initial regimen for a 60-year-oldpatient with del(17p) CLL who requires nibAcalabrutinibVenetoclax obinutuzumabAcalabrutinib labrutinib
What would be your most likely approach for a patient withnewly diagnosed CLL to whom you administer up-frontvenetoclax/obinutuzumab who has detectable MRD after 1 yearof treatment?1. Continue treatment2. Discontinue treatment
What would be your most likely approach for a patient withnewly diagnosed CLL to whom you administer up-frontvenetoclax/obinutuzumab who has detectable minimal residualdisease (MRD) after 1 year of treatment?Discontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentContinue treatmentContinue treatmentDiscontinue treatmentContinue treatment
What would be your most likely approach for a patient withnewly diagnosed CLL to whom you administer up-frontvenetoclax/obinutuzumab who has achieved undetectable MRDstatus after 1 year of treatment?Discontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatmentDiscontinue treatment
Which second-line systemic therapy would you recommend for a60-year-old patient with CLL with no IGHV mutation and nodel(17p) or TP53 mutation who responds to ibrutinib and thenexperiences disease progression 3 years later?1. Acalabrutinib2. Acalabrutinib obinutuzumab3. Venetoclax4. Venetoclax rituximab5. Venetoclax obinutuzumab6. Idelalisib7. Duvelisib8. Other
Which second-line systemic therapy would you recommend fora 60-year-old patient with CLL with unmutated IGHV and nodel(17p) or TP53 mutation who responds to ibrutinib and thenexperiences disease progression 3 years later?Venetoclax rituximabVenetoclax rituximabVenetoclax obinutuzumabVenetoclax rituximabVenetoclax rituximabVenetoclax obinutuzumabVenetoclax rituximabVenetoclax rituximabVenetoclax rituximabVenetoclax rituximabVenetoclax
Which second-line systemic therapy would you recommend for a 60-yearold patient with CLL with no IGHV mutation and no del(17p) or TP53mutation who responds to venetoclax/obinutuzumab and then experiencesdisease progression 3 years later?1. Ibrutinib2. Ibrutinib rituximab3. Ibrutinib obinutuzumab4. Acalabrutinib5. Acalabrutinib obinutuzumab6. Idelalisib7. Duvelisib8. Other
Which second-line systemic therapy would you recommend for a60-year-old patient with CLL with unmutated IGHV and no del(17p)or TP53 mutation who responds to venetoclax/obinutuzumab andthen experiences disease progression 3 years later?Venetoclax labrutinibIbrutinibAcalabrutinibVenetoclax rituximabVenetoclax rituximabIbrutinibAcalabrutinib
A 60-year-old patient with CLL, an absolute lymphocyte count of 20,000and several involved lymph nodes that are smaller than 2 centimeters isabout to receive venetoclax. What preemptive measures, if any, would youtake to address tumor lysis syndrome prior to the initiation of therapy?Encourage oral hydrationand allopurinolEncourage oral hydrationand allopurinolIV hydration and allopurinolGive the obinutuzumab first to debulk,then after 1 month can start as outpatientwith hydration and allopurinolEncourage oral hydrationand allopurinolEncourage oral hydrationand allopurinolEncourage oral hydrationand allopurinolEncourage oral hydrationand allopurinolIV hydration and allopurinolEncourage oral hydrationand allopurinolEncourage oral hydrationand allopurinol
A 60-year-old patient with CLL, an absolute lymphocyte count of 80,000and several involved lymph nodes that are larger than 5 centimeters isabout to receive venetoclax. What preemptive measures, if any, would youtake to address tumor lysis syndrome prior to the initiation of therapy?Admit to hospitalAdmit to hospitalDebulk with obinutuzumabObinutuzumab for 1 month tolower patient risk, then outpatienthydration and allopurinolAdmit to hospitalAdmit to hospitalAdmit to hospitalAdmit to hospitalAdmit to hospitalIV hydration and allopurinolAdmit to hospital
For your patients with CLL whom you admit to the hospital toreceive venetoclax, for how long do you typically admit them?8 days2 nights for each doseescalation2 days2 days2 days ( 48 hours)1- 2 days2 days2 days2-3 days2 days or rapid escalationto full dose over 5 days1 day
Meet The Professor with Dr WierdaMODULE 1: Cases from the Community (Drs Lamar, Morganstein, and Rupard)MODULE 2: CLL Journal Club with Dr WierdaMODULE 3: Beyond the Guidelines – Clinical Investigator Approaches to Common Clinical ScenariosMODULE 4: Key Recent Data Sets CAPTIVATE MRD cohort: Efficacy and safety results with ibrutinib lead-in and ibrutinib/venetoclaxcombination PFS and rate and duration of MRD negativity with venetoclax/obinutuzumab (CLL14 trial) Acalabrutinib for previously untreated CLL (ELEVATE-TN trial) Extended follow-up results with ibrutinib/rituximab in younger patients (ECOG-E1912 trial)
CAPTIVATE MRD Cohort: Study DesignMRD-guided randomizationConfirmed uMRDRandomize 1:1 (double-blind)Patients (N 164) Previously untreatedCLL/SLL Active diseaserequiring treatmentper iwCLL criteria Age 70 years ECOG PS 0-1IbrutinibIbrutinib lead-inIbrutinib 420 mgonce daily(3 cycles)Ibrutinib venetoclaxIbrutinib 420 mg once daily venetoclax ramp-up to 400 mgonce daily(12 cycles)PlacebouMRD not confirmedRandomize 1:1 (open-label)IbrutinibIbrutinib venetoclaxuMRD undetectable minimal residual diseaseResults presented for prerandomization phase of the MRD cohort (n 164) with 12 cycles ofibrutinib venetoclax prior to MRD-guided randomizationSiddiqi S et al. EHA 2020;Abstract S158.
CAPTIVATE MRD Cohort: 3 Cycles of Ibrutinib Lead-InALC by timepointReductions in lymph node burden after lead-in% Change in SPD from baseline 25 x 109/L 25 x 109/LPatients (%)Missing65763524BaselineAfter ibrutiniblead-inThree cycles of ibrutinib lead-in reduces TLS risk and indication for hospitalizationSiddiqi S et al. EHA 2020;Abstract S158.1
CAPTIVATE MRD Cohort: Undetectable MRD RateBest response of undetectable MRD in evaluable patients(95% CI)Peripheralbloodn 163Bone marrown 15575%(68-82)72%(64-79) Rates of undetectable MRD in peripheral blood and bone marrow were highlyconcordant at Cycle 16 (91%) In the all-treated population (N 164), undetectable MRD was achieved in 75%of patients in peripheral blood and in 68% of patients in bone marrow with upto 12 cycles of combination ibrutinib/venetoclaxSiddiqi S et al. EHA 2020;Abstract S158.
CAPTIVATE MRD Cohort: Undetectable MRD in Patients with CR/PRBest overall response (N 164)Patients, %ORR 97%Best overall response(up to Cycle 16)CRn 84PRn 75ORR (CR PR)n 159Undetectable MRD in PB, n (%)71 (85)52 (69)123 (77)Undetectable MRD in BM, n (%)67 (80)44 (59)111 (70)At 15 months, 98% of patients were progression free with no deathsSiddiqi S et al. EHA 2020;Abstract S158.
CAPTIVATE MRD Cohort: Summary of Grade 3 and 4 AEs of InterestIbrutinib lead-in(3 cycles)N 164AEs, n (%)Ibrutinib venetoclax combination(12 cycles)N 159Overall(15 cycles)N 164Grade 3Grade 4Grade 3Grade 4Grade 3-42 (1)01 (1)03 (2)001 (1)01 (1)Infections4 (2)010 (6)014 (9)Neutropenia4 (2)7 (4)27 (17)26 (16)58 (35)Febrile neutropenia1 (1)02 (1)03 (2)002 (1)02 (1)Atrial fibrillationMajor hemorrhageLaboratory TLS Low rates of Grade 3 atrial fibrillation, major hemorrhage, infections, febrile neutropenia and laboratory TLS(no Grade 4 event) No patients developed clinical TLS– Laboratory TLS reported as AE in 3 patients (only 1 met Howard criteria) No fatal AEsSiddiqi S et al. EHA 2020;Abstract S158.
Ongoing Phase III EA9161 Trial SchemaStratificationsAge: 65 yr vs 65 yr and 70 yrPS: 0, 1, vs 2Stage: 0, 1, or 2 vs 3, 4Del11q22.3 vs othersRandomizeArm AIbrutinib: Cycles 1-19:d1-28 420mg PO dailyObinutuzumab: C1 : D1:100 mg IV, D2:900 mg IV,D8: 1000 mg IV, D15: 1000 mg IV; C2-6: D1 1000 mg IVVenetoclax: C3 D1-7 20mg PO daily D8-14 50mg POdaily D15-21 100mg PO daily; D22-28 200 mg PO daily;C4-14: D1-28 400mg PO dailyArm BIbrutinib: Cycles 1-19 :d1-28 420mg PO dailyObinutuzumab: C1 : D1:100 mg IV, D2:900 mg IV,D8: 1000 mg IV, D15: 1000mg IV; C2-6: D1 1000 mg IVCourtesy of Brad Kahl, MD
CLL14 Phase III Study SchemaEligibility (n 432)Chlorambucil obinutuzumab(1:1) Previously untreated CLLrequiring treatment Total CIRS score 6RVenetoclax obinutuzumabPrimary endpoint: Progression-free survival Treatment duration in both groups: 12 cycles, 28 days eachNo crossover was allowedDaily oral venetoclax regimen: Initiated on day 22 of cycle 1, starting with a 5-week dose ramp-up (1 week each of 20,50, 100 and 200 mg, then 400 mg daily for 1 week) Thereafter continuing at 400 mg daily until completion of cycle 12www.clinicaltrials.gov (NCT02242942). Accessed August 2020.Fischer K et al. N Engl J Med 2019;380(23):2225-36.
CLL14: Investigator-Assessed Progression-Free SurvivalPercentage of uzumabEndpointVen-obin(n 216)Chlor-obin(n 216)HRp-valuePFS events30770.35 0.00124-mo PFS88.2%64.1%——Months to eventFischer K et al. N Engl J Med 2019;380(23):2225-36.
CLL14: PFS by IGHV Mutation StatusPercentage of patientsMedian PFSVen-Obi & IGHVmut: not reachedVen-Obi & IGHVunmut: not reachedClb-Obi & IGHVmut: 42.9 monthsClb-Obi & IGHVunmut: 26.3 monthsVEN-OBI & IGHV mutatedVEN-OBI & IGHV unmutatedCLB-OBI & IGHV mutatedCLB-OBI & IGHV unmutatedHR 1.96, p 0.08HR 2.98, p 0.001Months to eventAl-Sawaf O et al. EHA 2020;Abstract S155.
CLL14: Minimal Residual Disease 3 MonthsAfter TreatmentMRD-negativeMRD respondersMRD 3 months aftertreatmentVeneto/obin(N 216)Chloram/obin(N 216)Veneto/obin(N 216)Chloram/obin(N 216)MRD in bone marrow56.9%17.1%33.8%10.6%Odds ratio, p-valueMRD in peripheral bloodOdds ratio, p-valueFischer K et al. N Engl J Med 2019;380(23):2225-36.OR 6.4, p 0.000175.7%35.2%OR 5.7, p 0.0001OR 4.3, p 0.000142.1%14.4%OR 4.3, p 0.0001
Landmark progression-free survivalCLL14: Landmark Analysis from End ofTherapy PFS by MRD GroupClbG MRD(-) (N 76)ClbG MRD( ) (N 106)ClbG MRD Unknown (N 34)VenG MRD(-) (N 163)VenG MRD( ) (N 24)VenG MRD Unknown (N 29)CensoredTime since end of treatment (months)Further landmark analysis of PFS by MRD status showed that undetectable MRDtranslated into improved PFS regardless of the clinical response status at end oftherapy.Fischer K et al. ASH 2019;Abstract 36.
ELEVATE-TN Phase III Trial SchemaObinutuzumab chlorambucilAccrual: 535EligibilityPreviously untreated CLLRAcalabrutinibObinutuzumab acalabrutinibPrimary endpoint: Progression-free survivalwww.clinicaltrials.gov (NCT02475681). Accessed August 2020.
ELEVATE-TN: PFS (IRC)Progression-free survival (%)10080604020Acala obinAcalaClb obinMedian (95% CI)NR (NE–NE)NR (34.2–NE)22.6 (20.2–27.6)Hazard ratio p-value0.10 0.00010.20 0.0001.006Sharman JP et al. Lancet 2020;395:1278-91.121824Months303642
Phase III ECOG-ACRIN E1912 Study DesignIbrutinib rituximab (IR)à ibrutinib until PDEligibility Previously untreated CLLrequiring treatment Ability to tolerate FCRbased therapyR(2:1; N 529) Age 70 yearsFCRPrimary endpoint: PFSSecondary endpoints: OS, ORR, Toxicity and TolerabilityECOG-ACRIN E1912 Physician Fact Sheet, version 01/15/16;www.clinicaltrials.gov (NCT02048813); Shanafelt TD et al. ASH 2018;Abstract LBA-4.
ECOG-ACRIN E1912 Extended Follow-Up: Up-FrontIR Compared to FCR for Younger Patients with CLLProbabilityPFSHR 0.39p 0.00013-year rates: 89%, 71%FCR (52 events/175 cases)IR (58 events/354 cases)Number at riskYears Grade 3 treatment-related AEs were reported in 70% of patients receiving IR and80% of patients receiving FCR (odds ratio 0.56; p 0.013). Among the 95 patients who discontinued ibrutinib, the most common cause wasAE or complication.Shanafelt TD et al. ASH 2019;Abstract 33.
ECOG-ACRIN E1912 Extended Follow-Up:PFS by IGHV Mutation StatusHR 0.42p 0.0863-year rates: 88%, 82%No IGHV mutationProbabilityProbabilityIGHV mutationHR 0.28p 0.00013-year rates: 89%, 65%FCR (29 events/71 cases)IR (36 events/210 cases)FCR (8 events/44 cases)IR (10 events/70 cases)Number at riskYearsNumber at riskYears On subgroup analysis by IGHV mutation status, IR was superior to FCR for CLL withno IGHV mutation (HR 0.28; p 0.0001). With current follow-up the difference between IR and FCR is not significant for CLLwith IGHV mutation (HR 0.42; p 0.086).Shanafelt TD et al. ASH 2019;Abstract 33.
Meet The ProfessorManagement of Lung CancerMonday, October 5, 202012:00 PM – 1:00 PM ETFacultyProfessor Tony SK Mok, MDModeratorNeil Love, MD
Thank you for joining us!CME and MOC credit information will be emailedto each participant within 5 days.
GW Cancer Center Washington, DC Project Chair Neil Love, MD Research To Practice Miami, Florida. We Encourage Clinicians in Practice to Submit Questions . McGlinn Cancer Institute Reading Hospital and Medical Center West Reading, Pennsylvania. Blood 2020;135(17):1421-27 . Wierda Blood 2020
