aml and heme malignancies in patients with newly diagnosed … · 2019-11-02 · ldac vs ldac alone...

Overcoming Treatment Challenges in Patients with Newly Diagnosed AML and Heme Malignancies

1

Gary J. Schiller, MD

Conflict-of-Interest Disclosures• Research Support:

• Astellas Karyopharm Onyx

• Abvie Onconova Amgen

• Trovagene Kite Daiichi Sanyo

• Agios Gilead Jazz

• Celgene Forma Novartis

• Incyte Stemline

• Medimmune Bristol-Myers-Squibb

• Janssen Pharmacyclics

2

Introductory Patient History• 70 y.o. male with a history of 3 months of fatigue, sweats, and weight

loss. Initial WBC 16,400, Hgb 13, and platelet 175. Diff showed 8% metamyelocytes, 11% myelocytes and 4% promyelocytes

• A bone marrow biopsy identified hypercellularity of 100% with some left shift. Cytogenetics were normal, and molecular testing for bcr-abl and JAK2 were negative, but in the blood, ASXL1 and BCOR1 mutations were seen (5.9% and 13%)

• Progressive leukocytosis was noted over the next four months

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Continued Patient History• The patient developed back pain and weakness, and MRI showed low

signal material arising around the nerve roots

• CT-guided biopsy demonstrated a myeloid neoplasm

• Worsening back pain and leukocytosis prompted referral to an academic medical center

• Repeat bone marrow core biopsy showed 30-50% promonocytes and blasts. Cytogenetics were 46,XY, t(8;9)(p22;p24), der(9)

• Sequencing panel confirmed ASXL1 (vaf 41%)

4

Introductory Patient History• After achieving CR, with MRD-negativity by UW flow, the patient

elected to receive three cycles of high-dose cytarabine-based consolidation therapy

• Three years after CR1 was achieved, the patient developed low-back pain followed, over several months, by mild thrombocytopenia and leukopenia

• Repeat bone marrow identified 20% CD117-positive blasts. NPM1 allelic frequency 21%; no flt3 ITD identified.

5

Acute Myelogenous Leukemia• Defined by biologically distinct disease subsets defined by an

accumulation of molecular drivers of cell proliferation and survival

• Defined by clinically distinct subsets of patients with characteristic clinical features that define risk

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Definitions of High Risk AML• Clinical Variables

• Antecedent hematologic disturbance

• Advanced age at presentation

• History of exposure to cytotoxic agents and/or radiotherapy

• Gender

• Comorbid medical disease

• Biologic Variables• Adverse Cytogenetics

• Monosomies

• Complex (>3) abnormalities

• inv(3), t(3;3), t(6;9), t(6;11), t(9;22), 17p

• Other cytogenetic features (eg, 11q23)

• Alterations in gene expression, microRNA

• Recurrent single-gene mutations

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Newly Diagnosed AML • Clinically and biologically heterogenous• Although most arise de novo, many arise in the setting of

prior hematologic disease or after cytotoxic chemotherapy or radiotherapy

• Clinical factors are crucial in decisions regarding management, especially in older patients

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Clinical Presentation• 68 year old w/ 3 weeks of exertional fatigue, bleeding. WBC 73,000

• Bone Marrow biopsy diagnostic of AML characterized by 46, XY, inv (16) (p13.1q22) [14];

46, idem, del(17)(q23)[6]

• Induction with cytarabine/idarubicin followed by consolidation with IDAC x 2

• Remission duration 9 months. Relapse characterized only by inv(16)

• Reinduced with Clofarabine/Cytarabine. Treated with allotransplant from sibling after bu

(10)/ flu conditioning. Course complicated by moderate cGvHD

• Patient remains in remission 2 ½ years after allotransplant

9

Characteristics of Elderly Patients with Newly Diagnosed AML• Poor performance status

• Higher incidence of co-morbid disease

• Lower WBC at diagnosis

• Lower percentage of marrow blasts

• Higher likelihood of multidrug resistance

• Lower likelihood of “favorable” cytogenetics

• Lower likelihood of achieving remission

• Higher likelihood of treatment-related morbidity & mortality

• Lower likelihood of survival

10

Non-Intensive, Minimally Myelosuppressive Therapy• Low-dose cytarabine• Hypomethylating agents

• Azacytidine, Decitabine, Guadecitabine

• Targeted agents, alone or in combination with HMA• Agents targeting anti-apoptotic BCL-2

• Alone• In combination with hypomethylating agents

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Venetoclax plus Hypomethylating Agent Therapy• As a selective orally bioavailable inhibitor of BCL-2, single-agent activity

in R/R AML is limited

• In combination with HMA, significant activity in published phase 1 study• N=57. AEs included myelosuppression requiring interruption

• Median t to discontinuation= 2.8 months

• 61% CR/ CRi; median duration 8.4 months for all responding patientsDiNardo CD, et al. Lancet Oncol. 2018;19:216-28.

DiNardo CD, et al. Blood 2018; Oct.

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Venetoclax Combinations Described

• Maiti, et al. Abs. 286: with decitabine 20 mg/m2/d x 10

• Wei, et al. Abs. 284: with low-dose cytarabine 20 mg/m2/d x 10

• DiNardo, et al. Abs. 4048 with FLAG-Ida for patients with R/R disease

• Westley, et al. Abs. 1429 comparison of Ven-LDAC with Glasdegib-LDAC

• Similar response rates, depending on status of prior therapy and disease characteristics, with similar median response duration

13

FDA Approval of Venetoclax in Combination For Newly Diagnosed AML in Older Adults

• November 21, 2018: FDA expanded indication to include venetoclax in combination with either azacitidine, decitabine, or

low-dose cytarabine for newly diagnosed AML in adults who are either aged ≥ 75 yrs or have comorbidities precluding use

of intensive induction chemotherapy[1,2]

• New indication based on 2 open-label, nonrandomized phase I/II trials [2-4]

• In the M14-358 trial in newly diagnosed AML, the CR rate was 37% with venetoclax + azacitidine and 54% with

venetoclax + decitabine

• In the M14-387 trial in newly diagnosed AML, including those with prior hypomethylating agent for an antecedent

hematologic disorder, venetoclax + low-dose cytarabine was associated with a CR rate of 21%

§1. Venetoclax PI. 2. FDA. FDA approves venetoclax. Updated November 23, 2018. 3. NCT02203773. 4. NCT02287233.

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61 52 43 37 33 30 26 19 12 8 3 2 2 2 1

Venetoclax + LDAC in Untreated Older AML Patients: Phase I/II Studies

§1. Wei. ASH 2017. Abstract 890.

Durable ResponsesCR/CRi, OS

Duration of CR/CRi

OS

0102030405060708090100

Patie

nts (

%)

Mos0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

38 32 26 20 18 15 10 7 3 1 1Patients at Risk, n

| Censored observation

High Response Rate

ORR

15

Venetoclax + Hypomethylating Agents for Unfit AML

1. DiNardo. Blood. October 25, 2018.[Epub ahead of print.] 2. Dombret. Blood. 2015;126:291.3. Kantarjian. J Clin Oncol. 2012;30:2670.

DrugCR/CRi

Median OS (mos)

2-year OS

Aza2 28% 10.4 mos 22%

Dec3 17.8% 7.7 mos <20%

VEN + HMA 67% 17.5 mos 46%

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Alvocidib (Flavopiridol) + Chemotherapy for AML • Alvocidib: potent CDK9 inhibitor

• Downregulates transcription of target genes (MCL1) [1]

Response to FLAM or 7 + 3 in Phase II Trial of Patients With Newly Diagnosed AML[2]

Response, n (%) FLAM(n = 109)

7 + 3(n = 56)

CR/Cri 76 (70) 26 (46)

Failure to achieve CR 26 (24) 29 (52)

Early death 7 (6) 1 (2)

1. Nakajima. Cell Death Dis. 2014;5:e1052. 2. Zeidner. Haematologica. 2015;100:1172.

§ Phase 2 study in combination with CM in RR-AML ongoing with preliminary results here

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Glasdegib: Oral Inhibitor of Sonic Hedgehog Pathway• Glasdegib: selective, potent oral inhibitor of transmembrane

protein smoothened (SMO), a component of the Sonic Hedgehog (Hh) signaling pathway

• Decreased expression of genes involved in leukemia stem cell renewal and maintenance

• Overcomes therapy resistance in LSC and bulk AML cells

Munchhof. ACS Med Chem Lett. 2012;3:106.

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Sonic Hedgehog Signaling Pathway: Inactive vs. Active• Inactive (Absence of Hh ligand)

–PTCH1 inhibits SMO–SUFU facilitates degradation of GLI activators GLI repression

–Hh target genes are not expressed

• Active (Presence of Hh ligand)• SMO activated• GLI activators translocate to nucleus

• Hh target genes expressed• Hh pathway• Cell cycle• Anti-apoptotic genes

Irvine, Coplan. Blood. 2012;119:2196.

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FDA Approval of Glasdegib For AML in Adults With Older Age or Comorbidities• November 21, 2018: FDA approved glasdegib at 100 mg PO QD in combination with low-dose cytarabine (LDAC) for

newly diagnosed AML in adults either aged ≥ 75 yrs or with comorbidities precluding intensive induction chemotherapy [1,2]

• Approval based on multicenter, open-label, randomized phase II BRIGHT AML 1003 trial, which compared glasdegib +

LDAC vs LDAC alone in patients newly diagnosed with AML[2,3]

• Inclusion criteria: either aged ≥ 75 yrs, severe cardiac disease, ECOG PS of 2, or serum creatinine > 1.3 mg/dL

• After a median f/u of 20 mos, the median OS was 8.3 mos with glasdegib + LDAC vs 4.3 mos with LDAC (HR: 0.46;

P = .0002)

1. Glasdegib PI. 2. FDA. FDA approves glasdegib. Updated November 23, 2018. 3. NCT01546038.

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OS Benefit of LDAC + Glasdegib vs LDAC Alone in Unfit Elderly Patients With AML

• Phase II study in pts with AML and high-risk myelodysplastic

syndrome (N = 132)

88 8174 64 57 52 5047 4341 36 34 29 22 1815 1414 11 8 7 7 7 5 3 3 2 1 1 0

LDAC + Glasdegib

(n = 88)

LDACAlone

(n = 44)Median age, yrs (range)

77 (63-92) 75 (58-83)

Good/Int CG, n (%)

52 (60) 25 (57)

CR/CRi (n, %) 20 (23) 2 (4.5)Median OS (mos) 8.8 mos 4.9 mos

HR (95% CI) 0.501 (0.334-0.752)P = .0003

Cortes. Am J Hematol. 2018;93:1301.

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Treatment that Targets Defined Molecular Markers of AML• Roboz, et al. Abs. 561. Ivosidentib as single-agent therapy for newly diagnosed,

IDH1-mutated AML. CR rate 26.5% in 34 patients

• Stein, et al. Abs. 550. Enasidenib and Ivosidenib with induction cytotoxic therapy for IDH2- and IDH1-mutated AML.

• Cortes, et al. Abs. 563. Quizartinib as a single agent in R/R flt3-mutated AML

• Pratz, et al. Abs. 564. Gilteritinib with induction cytotoxic therapy, followed by maintenance treatment- 100% response in flt3-mutated AML

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• Somatic IDH1 and IDH2 mutations result

in accumulation of oncometabolite 2-HG

→ epigenetic changes, impaired

cellular differentiation

• mIDH identified in multiple solid

and hematologic tumors

• Enasidenib (AG-221): inhibitor of mIDH2

• Ivosidenib (AG-120): inhibitor of mIDH1

Isocitrate Dehydrogenase (IDH) Mutations in AML

mIDH1 mIDH2

% of AML patients ~6–10% ~9–13%

Citrate

Isocitrate

- KG

IDH1

NADPH

-KG

IDH2

Isocitrate

Citrate

NADPH

mIDH2

2-HG

mIDH1

2-HG2-HG

2-HG2-HG

Metabolic dysregulation

Mitochondrion

Cytoplasm

-KG-dependent dioxygenases

Nucleus

Epigenetic changesImpaired cellular differentiation

2-HG

Me

Me

Me

23

Ivosidenib (AG-120) induces durable remissions and transfusion independence in patients with IDH1-mutant

untreated AML: Results from a phase 1 dose escalation and expansion study

Gail J Roboz1, Courtney D DiNardo2, Eytan M Stein3, Stéphane de Botton4, Alice S Mims5, Gabrielle T Prince6,

Jessica K Altman7, Martha L Arellano8, Will Donnellan9, Harry P Erba10, Gabriel N Mannis11, Daniel A Pollyea12,

Anthony S Stein13, Geoffrey L Uy14, Justin M Watts15, Amir T Fathi16, Hagop M Kantarjian2, Martin S Tallman3,

Sung Choe17, David Dai17, Bin Fan17, Hongfang Wang17, Vickie Zhang17, Katharine E Yen17, Stephanie M

Kapsalis17, Denice Hickman17, Hua Liu17, Samuel V Agresta17, Bin Wu17, Eyal C Attar17, Richard M Stone18

Presented at the 60th American Society of Hematology (ASH) Annual Meeting, December 1–4, 2018, San Diego, CA, USA

1Weill Cornell Medical College, New York, NY; 2University of Texas MD Anderson Cancer Center, Houston, TX; 3Memorial Sloan Kettering Cancer Center, New York, NY; 4Institut Gustave Roussy, Villejuif, France; 5Ohio State University Wexner Medical Center,

Columbus, OH; 6Johns Hopkins Hospital, Baltimore, MD; 7Northwestern University, Chicago, IL; 8Winship Cancer Institute of Emory University, Atlanta, GA; 9Sarah Cannon Research Institute, Nashville, TN;

10University of Alabama at Birmingham, Birmingham, AL; 11UCSF Helen Diller Family Comprehensive Cancer Center , San Francisco, CA; 12University of Colorado School of Medicine, Aurora, CO; 13City of Hope Medical Centre, Duarte, CA; 14Washington

University School of Medicine, St Louis, MO; 15Sylvester Comprehensive Cancer Center, Miami, FL; 16Massachusetts General Hospital Cancer Center, Boston, MA; 17Agios Pharmaceuticals, Inc., Cambridge, MA; 18Dana-Farber Cancer Institute, Boston, MA

561

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1st Line Ivosidenib in Unfit AML with IDH1-mut• 500 mg PO daily (n=33)

*CR/CRh:4 2.4% )n=] (1495% CI, 25.5-[60.8

Median time to CR/CRh: 2.8 months) range 1.9-(12.9Duration of response CR+CRh CR Overall

responseMedian [95% CI] months NE [6.5, NE] NE [4.2, NE] NE [6.5, NE]

6 months 91.7% 77.8% 77.4%

12 months 66.7% 77.8% 59.5%Overall survival, median [95% CI], months 12.6 [4.5, 25.7]Duration of follow-up, median (range), months 23.1 (0.635.1)

Roboz et al, abstr. 561, ASH 2018*CRh – CR with partial hematologic recovery (i.e. CRi/CRp), n=4

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Ivosidenib or enasidenib combined with standard induction and consolidation chemotherapy in patients with newly diagnosed AML with an IDH1 or IDH2 mutation is safe,

effective, and leads to MRD-negative complete remissionsEytan M Stein1, Courtney D DiNardo2, Amir T Fathi3, Alice S Mims4, Keith W Pratz5, Michael R Savona6, Anthony

S Stein7, Richard M Stone8, Eric S Winer8, Christopher S Seet9,

Hartmut Döhner10, Daniel A Pollyea11, James K McCloskey12, Olatoyosi Odenike13, Bob Löwenberg14,

Gert J Ossenkoppele15, Prapti A Patel16, Mikhail Roshal1, Frederik Lersch17, Salah Nabhan18,

Sung Choe18, Hongfang Wang18, Lei Hua18, Caroline Almon18, Michael Cooper18, Martin S Tallman11Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Massachusetts General Hospital Cancer Center, Boston, MA, USA; 4Ohio State University Wexner Medical Center, Columbus,

OH, USA; 5Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; 6Vanderbilt-Ingram Center, VUMC, Nashville, TN, USA; 7City of Hope Medical Center, Duarte, CA, USA; 8Dana-Farber Cancer Institute, Boston, MA, USA; 9UCLA Medical Center, Los Angeles, CA, USA; 10Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany; 11University of Colorado School of Medicine, Aurora, CO, USA; 12Hackensack University Medical Center, Hackensack, NJ, USA; 3University

of Chicago Medicine Comprehensive Cancer Center, Chicago, IL, USA; 14Erasmus University Medical Centre, Rotterdam, Netherlands; 15VUmc Cancer Center, Amsterdam, Netherlands; 16University of Texas Southwestern Medical Center, Dallas, TX, USA; 7Celgene

International, Boudry, Switzerland; 18Agios Pharmaceuticals, Inc., Cambridge, MA, USA

560

Presented at the 60th American Society of Hematology (ASH) Annual Meeting, December 1–4, 2018, San Diego, CA, USA

26

1Altman JK, et al. Am J Hematol 93:213, 2018; 2Wang ES, et al. ASH 2017 Abstract 566;

3Pratz KW, et al. Abstract 564, ASH 2018

FLT3 Inhibitors and 7+3 Induction

Drug Half life D835 Selectivity FDA ApprovalR/R AML 7&3 Combination

Quizartinib (AC220)

Long(daily) No Narrow

(inhibits KIT) Not Approved Phase 1/2 complete1Phase 3 ongoing

Crenolanib Short(TID) Yes Narrow

(spares KIT)Ongoing pivotal

studiesPhase 2 complete2Phase 3 start 2018

Gilteritinib(ASP2215)

Long(daily) Yes Narrow

(spares KIT)FDA Approval

11/18Phase 1/2 complete3 - ASH 2018 report

Midostaurin: FDA-approved, OS advantage (‘RATIFY’), current standard of care

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Distinguishing Therapy-Related AML from Secondary AML• Definition:• AML presumed to be caused by exposure to chemotherapy or

radiotherapy for conditions other than myelodysplasia, myeloproliferative neoplasia, or an overlap disorder

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Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and Clinical Significance of Secondary and Therapy-Related AML. J Clin Oncol. 2015;33(31):3641-9.

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Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and Clinical Significance of Secondary and Therapy-Related AML. J Clin Oncol. 2015;33(31):3641-9.

31

Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and Clinical Significance of Secondary and Therapy-Related AML. J Clin Oncol. 2015;33(31):3641-9.Survival for intensive therapy patients and Overall with favorable cytogenetic risk

32

Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and Clinical Significance of Secondary and Therapy-Related AML. J Clin Oncol. 2015;33(31):3641-9. Survival for patients with adverse cytogenetic risk age less than 60 and age over 60.

AML with Myelodysplasia – Related Changes• Antecedent history of myelodysplasia or an overlap disorder (MDS/MPN)

• Multilineage dysplasia in 50% of at least two lineages in the absence of mutation in NPM1 or biallelic CEBPA mutation

• MDS-related cytogenetic abnormality(-ies)

• Distinct approaches- molecularly-defined targets, non-intensive strategies, pharmacologic manipulation of standard therapy

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Phase 3 trial in adults with newly-diagnosed t-AML or AML-MRC1,2

34

7+3 n=156

VYXEOS n=153

VYXEOS on Days 1, 3, and 5

309

Patie

nts Follow

-up

Induction Subsequent induction(if needed)a

Consolidation (1-2 cycles)b

(44 mg/100 mg per m2)

VYXEOS on Days 1 and 3

(44 mg/100 mg per m2 )

VYXEOS on Days 1 and 3

(29 mg/65 mg per m2)

7 days of cytarabine + 3 days of daunorubicin



(100 mg/m2/day + 60 mg/m2/day) (100 mg/m2/day + 60 mg/m2/day) (100 mg/m2/day + 60 mg/m2/day)

Key eligibility criteria for Phase 3 study1,3:� Previously untreated

� Aged 60-75

� Able to tolerate intensive therapy

� Performance status 0-2

Primary endpoint: Overall survival

aSubsequent induction was recommended for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts.

bPost-remission therapy with HSCT was permitted either in place of or after consolidation.

References: 1. VYXEOS [package insert]. Palo Alto, CA: Jazz Pharmaceuticals. 2. Data on file. VYX-2017-008. Palo Alto, CA: Jazz Pharmaceuticals. 3. Lancet JE, et al. Final results of a phase III randomized trial of VYXEOS™ (CPX-351) versus 7 + 3 in older patients with newly diagnosed high-risk

(secondary) AML. Oral presentation at: American Society of Clinical Oncology Annual Meeting; June 3-7, 2016; Chicago, IL.

35

Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) Liposome for Injection. J Clin Oncol. 2018;36(26):2684-2692.

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Allogeneic Hematopoietic Stem-Cell Transplantation in High-Risk AML

Author Study Population Preparative Regimen Outcome

Duval, et al. n = 1673AML relapsed or primary induction failure, retrospective registry study

Multiple Survival at 3 years: 19%Mortality at 100 days: 39%Cause of Death:AML in 42%

Koreth, et al. n = 6007,AML-CR1 meta-analysis donor vs. no donor

Multiple Significant benefit in survival for poor-risk and intermediate-risk

Sengsayadeth, et al.

n = 802 Secondary AML in CR1 retrospective registry study

Multiple- 40% MAC and 60% RIC

40% 2-year LFS, 46% 2-year OS

43

Sengsayadeth S, Gatwood KS, Boumendil A, et al. Conditioning intensity in secondary AML. Blood Adv. 2018;2(16):2127-2135.

44

Sengsayadeth S, Gatwood KS, Boumendil A, et al. Conditioning intensity in secondary AML. Blood Adv. 2018;2(16):2127-2135.

45

Sengsayadeth S, Labopin M, Boumendil A, et al. Transplant Outcomes for Secondary AML. Biol Blood Marrow Transplant. 2018;24(7):1406-1414.

Clinical Trials in Myeloproliferative Disease• Previously Untreated

• Open-label Phase 2 study of the safety and efficacy of INCB050465 in combination with Ruxolitinib in myelofibrosis

• A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 2 - Dose Expansion of CPI-0610 with and

without Ruxolitinib in Patients with Myelofibrosis

• Relapsed/Refractory

• A Randomized, Single-Blind, Multicenter Phase 2 Study of SL-401 in Patients with Advanced, High Risk Myeloproliferative

Neoplasms

• Samus PU-H71-01-003: Phase 1b Study of PU-H71 for the Treatment of Subjects with Primary Myelofibrosis (PMF), Post-

Polycythemia Vera Myelofibrosis (Post-PV MF) or Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), Treated with

Ruxolitinib

Clinical Trials in Myelodysplasia• Incyte INCB59872-101

• A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB059872 in

Subjects With Advanced Malignancies

• Imetelstat

• Telomerase inhibitor for patients with low or intermediate-1 risk myelodysplastic syndrome, transfusion dependent,

and relapsed/refractory to therapy with ESA

• Onconova 04-30 Rigosertib

• A Phase III, International, Randomized, Controlled Study of Rigosertib versus Physician’s Choice of Treatment in

Patients with Myelodysplastic Syndrome after Failure of a Hypomethylating Agent

Immunotherapeutic Options in Hematological Neoplasia

• Antibody-based therapy• Antibody-drug conjugates

• Gemtuzumab- CD33• Polatuzumab vedotin in NHL- CD79a

• Bifunctional Monoclonal Antibodies• Chimeric Antigen-Receptor T cells• Other Cell-Based Therapy

48

• GRIFFIN Trial: RVD +/- daratumumab

• Previously untreated patients eligible for ASCT1:1 Randomization

RVD +Dara RVD

Stem cell collection after cycle 4

4 Cycles

ASCT

Dara + Len Maintenance

Len Maintenance

2 Cycles ConsolidationsCR: 42%MRD: 59%

sCR: 32%MRD: 24%

In Start Up: BB2121-MM-004

High risk (HR) defined by IMWG: t(4;14), del17p, t(14;16), serum

LDH>ULN

Clinical Challenges of Treating Newly Diagnosed AML• Conclusions

• Assessment of risk • Defining therapy on the basis of biologic features and risk• Defining therapy on the basis of clinical features• Managing treatment-related adverse events • Managing risk of relapse through maintenance or consolidative strategies

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Acknowledgements:The Hematological Malignancy/Stem Cell Transplant Team:Gary SchillerWanxing Chai-HoJohn Chute

DeVosSven Herbert EradatJohn Glaspy

LarsonSarah Monica MeadCaspian OliaiJosh SasineChristopher SeetMary SehlHyung SuhJohn TimmermanPatricia Young

Nikki Alimi, NPMolly Oswald, NPBruck HabtemariamVlad KustanovichFarzam Hariri

The patients, nursing staff, and personnel at UCLA

Questions?

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References1. Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and Clinical Significance of Secondary and Therapy-

Related AML. J Clin Oncol. 2015;33(31):3641-9.2. Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) Liposome for Injection. J Clin Oncol.

2018;36(26):2684-2692.3. Schuler E, Zadrozny N, Blum S, et al. Long-term outcome of high risk patients with myelodysplastic syndromes or secondary

AML. Ann Hematol. 20184. Craig CM, Schiller GJ. Acute myeloid leukemia in the elderly: conventional and novel treatment approaches. Blood Rev.

2008;22(4):221-34.5. Sengsayadeth S, Gatwood KS, Boumendil A, et al. Conditioning intensity in secondary AML. Blood Adv. 2018;2(16):2127-2135.6. Bullinger L, Döhner K, Döhner H. Genomics of AML Diagnosis and Pathways. J Clin Oncol. 2017;35(9):934-946.7. Sengsayadeth S, Labopin M, Boumendil A, et al. Transplant Outcomes for Secondary AML. Biol Blood Marrow Transplant.

2018;24(7):1406-1414.8. Lindsley RC, Mar BG, Mazzola E, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood.

2015;125(9):1367-76.9. Miesner M, Haferlach C, Bacher U, et al. Multilineage dysplasia in AML correlates with MDS-related cytogenetic abnormalities.

Blood. 2010;116(15):2742-51.

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aml and heme malignancies in patients with newly diagnosed … · 2019-11-02 · ldac vs ldac alone...

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