Acute Leukemia. Julie Stakiw Saskatchewan Cancer Agency

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2 Acute Leukemia Julie Stakiw Saskatchewan Cancer Agency

3 Back in my day ACUTE LEUKEMIA

4 What s New in 2017

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6 Targeted Therapy Improves Survival N Engl J Med 2017; 377: August 3, 2017DOI: /NEJMoa

7 2017 FDA Approvals The U.S. Food and Drug Administration today approved Mylotarg (gemtuzumab ozogamicin) for the treatment of adults with newly diagnosed acute myeloid leukemia whose tumors express the CD33 antigen (CD33-positive AML). On April 28, the Food and Drug Administration (FDA) approved the addition of the targeted therapy midostaurin (Rydapt ) for adults receiving chemotherapy for newly diagnosed acute myeloid leukemia (AML) with certain mutations in the FLT3 gene.

8 Vyxeos (daunorubicin and cytarabine) ; Jazz Pharma; For the treatment of newlydiagnosed therapy-related AML or AML with myelodysplasia-related changes, Approved August 2017 IDHIFA (enasidenib); Celgene; For the treatment of relapsed or refractory acute myeloid leukemia with IDH2 mutation, Approved August 2017

9 CAR-T

10 On August 30, 2017, the Food and Drug Administration (FDA) approved a type of immunotherapy called CAR T-cell therapy for certain children and young adults with a form of acute lymphoblastic leukemia (ALL). The treatment, tisagenlecleucel (Kymriah ), is the first CAR T-cell therapy to receive FDA approval. ASH 2017 Special Session on CAR-T: Dec. 9, 4-5:30pm

11 NOC and PCODR CADTH pan-canadian Oncology Drug Review Blinotumomab: Date of Decision: April 18, 2016 Midostaurin (Rydapt):Date of decision: June 20, 2017

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13 ASH 2017 Abstracts 1533 acute leukemia abstracts (oral and poster sessions) 382 oral sessions Themes Precision/Personalized Therapy Mutational analysis MRD Maintenance Therapy New Drugs CAR-T (Phase I, Phase I/II)

14 LBA-5 Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML Program: General Sessions Session: Late-Breaking Abstracts Session Tuesday, December 12, 2017, 7:30 AM-9:00 AM Bldg C, Lvl 1, Hall C2-C3 (Georgia World Congress Center) Mojca Jongen-Lavrencic, MD, PhD 1, Tim Grob, MD 1*, Francois G. Kavelaars 1*, Adil S.A. Al Hinai 1*, Annelieke Zeilemaker 1*, Claudia A.J. Erpelinck-Verschueren 1*, Yvette Norden 2*, Rosa Meijer, PhD 2*, Bart J. Biemond, MD, PhD 3*, Carlos Graux 4*, Marinus van Marwijk Kooij, MD, PhD 5*, Markus G. Manz, MD 6, Thomas Pabst, MD, PhD 7, Violaine Havelange, MD, PhD 8*, Jakob R. Passweg, MD, PhD 9*, Gert J. Ossenkoppele, MD, PhD 10, Gerrit Jan Schuurhuis, PhD 10*, Mathijs A. Sanders, PhD 1*, Bob Löwenberg, MD, PhD 1 and Peter J.M. Valk, PhD 1

15 Abstract Information MRD detection in AML by PCR is restricted to specific genetically-defined subsets of AML only NGS allow for the assessment of a broader range of disease-related gene mutations in a single assay It s unknown which pre-existing somatic mutations after induction therapy contribute to AML relapse NGS performed to look at 54 genes frequently mutated in myeloid malignancies at diagnosis and morphological CR Primary Endpoint: Relapse (Cumulative Incidence of Relapse (CIR) Secondary Endpoint: Overall Survival

16 Results 89.2% AML patients had somatic mutations at diagnosis 54% at CR DTA mutations (DNMT3A, TET2, ASXL1) alone not associated with increased relapse DTA mutations with any other persisting mutation corresponded to increased relapse 5 year CIR 39.4% vs 76.4% Multivariable Analysis of 430 AML patients, NGS MRD was independently prognostic for relapse and survival

17 463 Randomized Maintenance Therapy with Azacitidine (Vidaza) in Older Patients ( 60 years of age) with Acute Myeloid Leukemia (AML) and Refractory Anemia with Excess of Blasts (RAEB, RAEB-t). Results of the HOVON97 Phase III Randomized Multicentre Study (EudraCT ) Program: Oral and Poster Abstracts Type: Oral Session: 613. Acute Myeloid Leukemia: Clinical Studies: Advances in Frontline Therapy: Induction, Consolidation, and Maintenance Sunday, December 10, 2017: 4:30 PM Bldg B, Lvl 5, Murphy BR 1-2 (Georgia World Congress Center) Geert Huls, MD, PhD 1, Dana Chitu 2*, Violaine Havelange, MD, PhD 3*, Mojca Jongen-Lavrencic, MD, PhD 4, Arjen van de Loosdrecht 5*, Bart J. Biemond, MD, PhD 6, Harm Sinnege, MD PhD 7*, Beata Hodossy 8*, Carlos Graux 9*, Marinus van Marwijk Kooij, MD, PhD 10*, Okke de Weerdt, MD 11, Dimitri A. Breems, MD, PhD 12*, Saskia Klein, MD 13*, Jurgen Kuball, MD 14, Gert J. Ossenkoppele, MD, PhD 15, Bob Löwenberg, MD, PhD 16 and Edo Vellenga, MD 17

18 Abstract Information Randomized Phase III study in patients > 60 years old AML or MDS-RAEB in CR after at least 2 cycles of intensive chemo Aza vs observation Primary Endpoint: DFS (1 year increase from 40-60% Secondary Endpoint: OS

19 Results 31 patients received Aza off protocol After relapse 9 went on to Allo After censoring out the Allo patients there was an OS of 83 vs 64% Both DFS and OS improved with maintenance Azacitidine

20 886 Role of Remission Status and Prior Transplant in Optimizing Survival Outcomes Following Allogeneic Hematopoietic Stem Transplantation (HSCT) in Patients Who Received Inotuzumab Ozogamicin (INO) for Relapsed / Refractory (R/R) Acute Lymphoblastic Leukemia (ALL) Program: Oral and Poster Abstracts Type: Oral Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Immune-based therapies and rare subgroups Monday, December 11, 2017: 7:00 PM Bldg C, Lvl 3, Georgia BR 1-3 (Georgia World Congress Center) Partow Kebriaei, MD 1, Matthias Stelljes, MD 2, Daniel J. DeAngelo, MD, PhD 3, Nicola Goekbuget, MD 4, Hagop M. Kantarjian, MD 5, Anjali S. Advani, MD 6, Akil Merchant, MD 7, Wendy Stock, MD 8, Tao Wang, PhD 9*, Hui Zhang 10*, Fausto Loberiza 11*, Erik Vandendries, MD, PhD 12* and David Marks 13

21 Abstract Information Inotuzumab Ozogamicin (INO) is an anti CD22 antibody conjugated to calicheamicin 2016, Kantarjian, NEJM When should INO be used in R/R ALL Patients with respect to transplant? Analysis population consisted of R/R ALL patients enrolled and treated with INO and proceeded to Allo-SCT as part of 2 trials

22 Results Conclusion: Administration of INO in R/R ALL patients followed by Allo-sct provided Best long term survival benefit among Those who went directly to HSCT after attaining remission and had no prior HSCT

23 888 Phase 1 Results of ZUMA-3: KTE-C19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL) Program: Oral and Poster Abstracts Type: Oral Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Immune-based therapies and rare subgroups Monday, December 11, 2017: 7:30 PM Bldg C, Lvl 3, Georgia BR 1-3 (Georgia World Congress Center) Bijal D. Shah, MD 1, Wendy Stock, MD 2, William G Wierda, MD, PhD 3, Olalekan Oluwole, MBBS, MPH 4*, Houston Holmes, MD, FACP 5, Gary J. Schiller, MD, FACP 6, Max S. Topp, MD 7, Marie José Kersten, MD, PhD 8, Roch Houot, MD, PhD 9*, Nicolas Boissel, MD, PhD 10, Michelle Mojadidi, MSc 11*, Allen Xue, PhD 11*, Armen Mardiros, PhD 11, Yizhou Jiang, PhD 11*, Tong Shen, PhD 11*, Jeff S. Aycock 11*, Shanna Stout 11*, Jeffrey S. Wiezorek, MD, MS 11* and Rajul Jain, MD 11

24 Abstract Information Primary Endpoint: DLT s Secondary Endpoints: AE s, MRD, DOR, RFS, OS 16 patients 50% > previous lines of therapy 31% primary refractory disease

25 Results No DLT s 1 grade 5 CRS, Tocilimumab given to 94% 11 patients available for efficacy analysis 73% CR, all remissions were MRD- Median Follow-up 6.8mo To be presented: Data from additional patients, additional doses Safety efficacy and biomarkers

26 Thank you! Enjoy Atlanta, GA and ASH 2017