Upload
others
View
6
Download
0
Embed Size (px)
Citation preview
4/14/2016
1
April 14, 2016
MDS: Update on Treatment and Side Effects Management
Azra Raza, MDProfessor of MedicineDirector, MDS CenterColumbia University Medical CenterMilstein Hospital BuildingNew York, NY
Antonietta de los Reyes, MSN, OCN®, FNP-CMDS CenterColumbia University Medical CenterHerbert Irving PavilionNew York, NY
Welcome and Introductions
CLL: Update on Treatment andSide Effects Management
MDS: Update on Treatment and Side Effects Management
4/14/2016
2
Disclosures
Azra Raza, MD does not have any relevant financial
relationships with any commercial interests to disclose.
Antonietta de los Reyes, MSN, OCN®, FNP-C does not have
any relevant financial relationships with any commercial
interests to disclose.
MDS: Update on Treatment and Side Effects Management
Azra Raza, MDProfessor of Medicine
Director, MDS Center
Columbia University
New York
Myelodysplastic Syndromes: Treatment and Side Effects Management
4/14/2016
3
WHAT IS MDS?
Divide Mature
Blood formation
Hea
lth
y A
du
lt
Blood
RBC
WBC
Platelets
Divide Mature and Die
MD
S A
du
lt
AnemiaNeutropenia
Thrombocytopenia
Trillion cells every 24 h.
Divide Do not mature
AM
L A
du
lt
AML
4/14/2016
4
IPSS for Risk Stratification
Greenberg P et al. Blood. 1997;89:2079-2088.
Score Value
Prognostic variable 0 0.5 1.0 1.5 2.0
Bone marrow blasts < 5% 5% to 10% -- 11% to 20% 21% to 30%
Karyotype* Good Intermediate Poor -- --
Cytopenias† 0/1 2/3 -- -- --
Accurately predicts prognosis in ~39% patients
A Prognostic Nightmare
YEARS
4/14/2016
5
IPSS-R -- 2012
Greenberg P L et al. Blood 2012;120:2454-2465
A case
• A 62-year-old man was discovered to have
borderline cytopenias:
– Hgb 11 g/dL
– WBC 3.6
– Platelet count 162,000
– BM did not meet the minimal criteria for MDS (<10%
dysplastic cells)
4/14/2016
6
Idiopathic Cytopenia(s) of Undetermined (Uncertain)
Significance (ICUS)
1) Meaningful cytopenias
2) Does not meet minimal diagnostic criteria for MDS
• > 10% dysplastic cells, or
• 5%-19% blasts, or
• Abnormal karyotype typical for MDS
ICUS
Valent P, et al. Leuk Res. 2007;31(6):727-736; Valent P and Horny HP. Eur J Clin Invest. 2009;39(7):548-553.
ICUS Natural History
Hanson C and Steensma D. Abstract presented at: MDS Symposium; May 2009; Patras, Greece.
2,899 marrow exams for cytopeniasat Mayo Clinic over 13 years
1,716: MDS535: non-MDS
neoplasmsMDS-U579: ?
59% 18% 20% 2%
4/14/2016
7
Case Continued…
• Genetic profiling shows a mutation in TET2
• ICUS to CHIP
CHIP as a precursor state for hematological neoplasms.
David P. Steensma et al. Blood 2015;126:9-16
4/14/2016
8
Morphologic Subtypes
Cytogenetics
Genetic Mutations
Response to Therapy
Personalization: selection of homogenous groups
MDS Treatment Options
4/14/2016
9
•Stem cell transplantCurative
RIC Allo-transplant in MDS between 60-70 years
1. Koreth J, Pidala J, Perez WS, et al. J Clin Oncol. 2013;31(21):2662-2270. 2. Cutler CS, Lee S, Greenberg P, et al. Blood. 2004;104(2):579-585.3. Malcovati L, Porta MG, Pascutto C, et al. J Clin Oncol. 2005;23(30):7594-7603. 4. Garcia-Manero G, Shan J, Faderl S, et al. Leukemia. 2008;22(3):538-543.
IPSS Low/Int-1 IPSS Int-2/High
1.0
0.8
0.6
0.4
0.2
0 20 40 60 80 100 120 140
Time (months)
Overa
ll S
urv
ival (p
rob
ab
ility
)
P<.001
Nontransplant therapy
RIC transplant
1.0
0.8
0.6
0.4
0.2
0 20 40 60 80 100 120 140
Time (months)
Overa
ll S
urv
ival (p
rob
ab
ility
)
P<.001
Nontransplant therapy
RIC transplant
RIC, reduced intensity conditioning.
4/14/2016
10
• ESA
• Lenalidomide
• Hypomethylatingagents
Palliative
Algorithm for treating lower risk MDS
Low and Int-1
5q- deletion± other cytogenetic
alterations?
Yes Lenalidomide
No
SerumEPO ≤500 mU/mL?
EPO ± G-CSFSupportive care
Clinical trial
LenalidomideAzacitidineDecitabine
ATG ± cyclosporineSupportive care
Clinical trial
Yes No
4/14/2016
11
Epo Improves Anemia in a Subset of Patients With MDS
• According to a meta-analysis, mean response rates range from 15% to 20%1
• Predictors for good response include serum Epolevel and transfusion need1
– <500 U/L and limited prior need for transfusion1
• Most responses to ESA occur within 8 weeks of treatment, some patients respond after 12 weeks2,3
1. Hellström-Lindberg E, Gulbrandsen N, Lindberg G, et al. Br J Haematol. 2003;120(6):1037-1046. 2. Ludwig H. Semin Oncol. 2002;29(3 suppl 8):45-54. 3. Casadevall N, Durieux P, Dubois S, et al. Blood. 2004;104(2):321-327.
15%-20%
8 weeks
ESA, erythropoiesis-stimulating agent.
LENALIDOMIDE
Transfusion-dependent anemia due to low- or Int-1–risk MDS associated with del(5q) with or without additional abnormalities
221. Revlimid [prescribing information]. Summit, NJ: Celgene Corp; 2013. 2. List A, Dewald G, Bennett J, et al. N Engl J Med. 2006;355(14):1456-1465. 3. Raza A, Reeves JA, Feldman EJ, et al. Blood. 2008;111(1):86-93.
Responders Nonresponders
4/14/2016
12
Lenalidomide Toxicity
• Allergic reactions
– Scalp itching
– Rash
– Controlled mostly by Benadryl® (diphenhydramine), occasional steroid use
• Diarrhea
– Lomotil® (diphenoxylate and atropine)
• Myelosuppression
N Engl J Med. 2006;355(14):1456-1465.Blood. 2008;111(1):86-93.
4/14/2016
13
Dose Modification
• Reserved for patients experiencing a 50% or greater decline in ANC or platelet count
• Treatment with Lenalidomide should be held until toxicity resolves and then resumed as follows
– 5mg/day for patients at 10mg/day
– 5 mg/every other day
– 5 mg twice weekly dose as long as there are no signs of disease progression
N Engl J Med. 2006;355(14):1456-1465.Blood. 2008;111(1):86-93.
HMAs in Lower Risk MDS
• Limited data
– In transfusion-dependent, lower-risk MDS resistant to ESA, HMA therapy results in approximately 17% transfusion independence
1. Vidaza [prescribing information]. Summit, NJ: Celgene Corp; 2012. 2. Dacogen [prescribing information]. Woodcliff Lake, NJ: Eisai Inc; 2010.3. Kantarjian H, Issa JP, Rosenfeld CS, et al. Cancer. 2006;106(8):1794-803. 4. Fenaux P, Adès L. Blood. 2013;121(21):4280-4286.
4/14/2016
14
Algorithm for treating higher risk MDS
Is a donor available
for
bone marrow
transplantation?
Yes
No
Bone marrow
transplantation
High/
Int-2
patient
Is the patient fit for
transplantation?Yes
No
Hypomethylating agents
Adapted from NCCN Guidelines on Myelodysplastic Syndromes V.1.2009.
ResponseExperimental
Drugs
Azacitidine (VIDAZA®) Efficacy: CALGB 9221
• Clinical Benefit
• 40% of patients treated with VIDAZA experienced clinical benefit
• 16% responded (CR + PR) and 24% improved
*Per the Study 9221 response criteria.†Patients who had positive changes in peripheral counts but did not meet criteria for CR or PR were considered improved.
VIDAZA full prescribing information.
4/14/2016
15
VIDAZA®: Most Commonly Occurring Adverse Reactions
(All Grades) in CALGB Studies 9221 and 8921 (SC Route)
Preferred Term(CALGB Criteria)
Observation n = 92 (%)
All VIDAZA (SC) n = 220 (%)
Nausea 16 (17.4) 155 (70.5)
Anemia 59 (64.1) 153 (69.5)
Thrombocytopenia 42 (45.7) 144 (65.5)
Vomiting 5 (5.4) 119 (54.1)
Pyrexia 28 (30.4) 114 (51.8)
Leukopenia 27 (29.3) 106 (48.2)
Diarrhea 13 (14.1) 80 (36.4)
Injection site erythema 0 77 (35.0)
Constipation 6 (6.5) 74 (33.6)
Neutropenia 10 (10.9) 71 (32.3)
Ecchymosis 14 (15.2) 67 (30.5)
VIDAZA full prescribing information.
Study 9221: Maximizing Response With VIDAZA®
• Achievement of PR was initially reported between the 2nd and 19th treatment cycles*
• Achievement of CR was between the 8th and 15th treatment cycles†
• Continue therapy beyond the initial benefit to achieve full benefit for patients
Celgene Corporation, Data on File.
*The median number of cycles needed to achieve a PR was 7†The median number of cycles needed to achieve a CR was 8
21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21Treatment
Cycles
Achievement of PR
Achievement of CR
4/14/2016
16
Azacitidine Treatment Prolongs Overall Survival in Higher-Risk MDS Patients
Compared with Conventional Care Regimens: Results of the
AZA-001 Phase III Study
P Fenaux, MD, GJ Mufti, MD, V Santini, MD, C Finelli, MD, A Giagounidis, MD, R Schoch, MD,A List, MD, S Gore, MD, J Seymour, MD, E Hellstrom-Lindberg, MD, J Bennett, MD,
J Byrd, MD, J Backstrom, MD, L Zimmerman, BSN, D McKenzie, MS, CL Beach, PharmD and L Silverman, MD
on behalf of the International Vidaza High-Risk MDS Survival Study Group
Overall Survival: Azacitidine vs CCR ITT Population
Log-Rank p=0.0001
Time (months) from Randomization
Pro
port
ion
Su
rviv
ing
CCR
AZA
Difference: 9.4 months
24.4 months
15 months
50.8%
26.2%
4/14/2016
17
Meaningful responses to both drugs generally short-lived in small subsets of patients
Bo
ne
M
arro
w
Time
MDS Stem Cell
4/14/2016
18
Genomics in Cancer Care
What is genomics? Genomics is the study of the entire genome
Genomics
Genomics in Cancer Care
What is genomics? Genomics is the study of the entire genome
“PANOMICS”
4/14/2016
19
Will this cure MDS?
Convert MDS into a chronic disease that patients can live with and not die from
More Than One Way to Build Bridges!Proud to partner in the MOONSHOT 2020
VIEW FROM MY OFFICE AT COLUMBIA UNIVERSITY MEDICAL CENTER
4/14/2016
20
Managing Treatment Side Effects of MDS
Antonietta De Los Reyes, MSN, OCN, FNP-CSMDS Center
Columbia University Medical CenterHerbert Irving Pavilion
New York, NY
Common Side Effects of Treatments
A. Erythropoietin Stimulating Agents (ESA):
• Procrit® (epoetin alfa) or Aranesp® (darbepoetin alfa) – SQ (weekly or bi-weekly) Hgb < 10 gms
• S/E:
– Headaches
– Body aches
• Management:
– Acetaminophen
4/14/2016
21
B. Lenalidomide – 10 mg podaily x 28 days every month
• S/E:̶ Myelosuppression̶ Allergic reactions- rash/scalp
itching̶ Diarrhea
• Management:̶ Weekly blood counts̶ Dose modifications̶ Growth factors̶ Transfusions̶ Antibiotics̶ Antihistamine/Steroids̶ Anti-diarrhea
C. Hypomethylathing Agents:Azacitidine and Decitabine – IV or SQ for 5 or 7 days every 4 weeks
• S/E:– Nausea – Cytopenias– Constipation – Infection
• Management:– Antiemetics (e.g. Kytril®/Zofran®)– Transfusions– Growth factors– Stool softener/laxatives (e.g. Colace®/Miralax®)– Antibiotics– Dose modifications – dose delay and dose reduction
4/14/2016
22
D. Iron Chelating Agents:
Deferasirox (Exjade® or Jadenu®) – oral once daily
• S/E:– Abdominal pain
– Diarrhea
– Nausea and vomiting
– Rash
• Management:– Antidiarrheals (e.g. Imodium®, Lomotil)
– Antiemetics (e.g. Kytril, Zofran)
– Antihistamines (e.g. Benadryl)
– Steroids – Topical or Medrol® dose pack
– Dose modifications
Patient Assistance:www.oncologyaccessnow.com/index.jsp - Novartiswww.revlimid.com/mm-patient/affording-revlimid/financial-assistance - Celgenewww.panfoundation.org - Patient Access Network Foundationwww.LLS.org/copay - The Leukemia & Lymphoma Society
MDS Resources:www.LLS.org/MDSwww.LLS.org/educationvideoswww.mdsbeacon.com/links/support-groupswww.mds-foundation.org/global-patient-support-groupswww.mdscenterfornurses.com/nurse-and-patient-resourceswww.aamds.org
4/14/2016
23
References:
Cancer. Net (2015). MDS: Coping with Side Effects. Retrieved from www.cancer.net/cancer-types/myelodysplastic-syndromes-mds/coping-side-effects
Chemocare. Retrieved from www.chemocare.com/chemotherapy/side-effects/default.aspx
Besa E. & Krishnan K, et al. Myelosdysplastic Syndrome Treatment & Management (12/6/2015) retrieved from
emedicine.medscape.com/article/207347-treatment
MDS: Update on Treatment and Side Effects Management
Question & Answer SessionThe speakers’ slides are available for download at
www.LLS.org/CE
4/14/2016
24
MDS: Update on Treatment and Side Effects Management
The Leukemia & Lymphoma Society (LLS) offers:
•Live, Online Chats provide a friendly forum for patients to share experiences:
www.LLS.org/chat
•What to ask: Lists of suggested questions for patients to ask the healthcare team.
Share question guides with your patients: www.LLS.org/whattoask
•LLS Online Social Network for HCPs and patients to seek answers and share
information: www.CommunityView.LLS.org
Information Resource Center:
Speak one-on-one with an Information Specialist who can assist
patients and healthcare professionals through cancer treatment,
including clinical trial searches, financial and social challenges.
EMAIL: [email protected]
TOLL-FREE PHONE: (800) 955-4572
MDS: Update on Treatment and Side Effects Management
The Leukemia & Lymphoma Society (LLS) offers:
Free education materials:
www.LLS.org/publications
Continuing education programs and
videos: www.LLS.org/professionaled