Cancer By the Numbers - Baptist Health South...
Transcript of Cancer By the Numbers - Baptist Health South...
7/14/2019
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What Primary Care Providers Need to Know About Blood Cancers
Steven Fein, MD, MPHHematologist/OncologistMiami Cancer InstituteBaptist Health South Florida
Disclosures
Dr. Fein is on speakers’ bureaus for:Bayer, Incyte, Seattle Genetics,Janssen, and Novartis.
This lecture will not discuss off-label uses for any medications.
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Learning Objectives
• Describe common blood cancers
• Determine when abnormal CBC warrants more testing or heme referral
• Understand blood cancer treatments
Cancer By the Numbers
• 18M new cancer patients/year in the world• 10M cancer-related deaths/year in the world
• 1.8M new cancer patients/year in the U.S.• 600K cancer-related deaths/year in the U.S.• 1 in 3 of us will get cancer in our lifetime
• 17M people living with cancer in the U.S.“cancer survivors” and “cancer fighters”
How We Die in the U.S. Cancer Body Count
Cancer Statistics, 2018. CA Cancer J Clin; 68:7-30.
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Cancer Body Count Nixon 12/23/71: War on Cancer
“The time has come in America when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease.”
https://dtp.cancer.gov/timeline/flash/milestones/M4_Nixon.htm
Important Book About the History of Cancer
Mukherjee, S. 2011. Emperor of All Maladies: A Biography of Cancer. Simon & Schuster Canada
Bending the Cancer Survival Curve
Source: 25 Year Decline of Cancer Death Rate. Cancer Health, American Cancer Society, January, 2019
What is the Goal of Therapy?
• Surgery if possible
• Aggressive, toxic chemotherapy
+/- radiation
• Support patients through complications
• Surgery for GI tumors
• Less toxic chemo
• Biologic therapies
• Immunotherapy
• Radiation for symptoms
• Longevity and QOL
Going for cure Palliative therapy
What is the Goal of Therapy?
• Surgery if possible
• Aggressive, toxic chemotherapy
+/- radiation
• Support patients through complications
• Surgery for GI tumors
• Less toxic chemo
• Biologic therapies
• Immunotherapy
• Radiation for symptoms
• Longevity and QOL
Going for cure Palliative therapy
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Modern Anti-Tumor Therapy Blood Cancers are 10% of the Pie
Categories of Cancer
Carcinoma
Blood cancers
Melanoma
Sarcoma
Brain tumors
What are the Blood Cancers?
• Leukemia– AML, APL, ALL, CML, CLL– PLL (Prolymphocytic leukemia)– Hairy Cell leukemia
• Lymphoma– Hodgkin’s Disease– NHL: DLBCL, FL, SLL/CLL, MCL, MZL
• Multiple Myeloma– Amyloidosis– Waldenstrom’s Disease
Potentially Curable by Chemo
APL leukemia 95%
CML leukemia 90%
Hodgkin’s lymphoma 90%
Large B cell lymphoma 60%
Adults with ALL leukemia 50%
Adults with AML leukemia 25%
What is Leukemia?
• Too many white blood cells
• Malignant tumor of the blood
• Malignant tumor of bone marrow
• Myeloid or lymphoid (lineage)
• Acute or chronic (maturation of cells, rate of growth)
Acute myeloid
AML, APL
Acute lymphoid
ALL
Chronic myeloid
Myeloproliferative
CML
PCV
ET
myelofibrosis
Chronic lymphoid
Lymphoproliferative
CLL/SLL
lymphoma
myeloma
What is Leukemia?
• Too many white blood cells
• Malignant tumor of the blood
• Malignant tumor of bone marrow
• Myeloid or lymphoid (lineage)
• Acute or chronic (maturation of cells, rate of growth)
Acute myeloid
AML, APL
Acute lymphoid
ALL
Chronic myeloid
Myeloproliferative
CML
PCV
ET
myelofibrosis
Chronic lymphoid
Lymphoproliferative
CLL/SLL
lymphoma
myeloma
One of the main reasons to do outpatient CBC’s is screening healthy people for leukemia.
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Why do screening CBC’s?
• Screening healthy people for leukemia
• Screening for “nutritional anemia” like iron deficiency
• Screening for other heme malignancy:
multiple myeloma, or MDS/MPD
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Abnormal CBC
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Which Leukemia is it?
• AML
• APL
• ALL
• CML
• CLL/SLL
• PLL
• Hairy Cell
Which Leukemia is it?
• AML
• APL
• ALL
• CML
• CLL/SLL
• PLL
• Hairy Cell
Which Leukemia is it?
• AML
• APL
• ALL
• CML
• CLL/SLL
• PLL
• Hairy Cell
Which Leukemia is it?
• AML
• APL
• ALL
• CML
• CLL/SLL
• PLL
• Hairy Cell
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Which Leukemia is it?
• AML
• APL
• ALL
• CML
• CLL
• PLL
• Hairy Cell
Which Leukemia is it?
• AML
• APL
• ALL
• CML
• CLL/SLL
• PLL
• Hairy Cell
Which Leukemia is it?
• AML
• APL
• ALL
• CML
• CLL/SLL
• PLL
• Hairy Cell
What to do With Patients who haveHigh WBC Count but No Infection
• Look at clinical picture, chronicity
• Look at WBC differential
• Look at plt count (high plt count=MPD)
• Flow cytometry ONLY FOR LYMPHS
• Consider imaging if lymphoma suspected
Abnormal CBC
29Diagnosis: CML
Chronic Myeloid Leukemia
Acute myeloid
AML, APL
Acute lymphoid
ALL
Chronic myeloid
Myeloproliferative
CML
PCV
ET
myelofibrosis
Chronic lymphoid
Lymphoproliferative
CLL/SLL
lymphoma
myeloma
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Normal Chronic phase CML
CML Blood Smear
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1 2 3 4 5
6 7 8 10 119 12
13 14 15 16 17 18
19 20 21 22X Y
Cytogenetic Abnormality of CML: Philadelphia Chromosome
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• Imatinib mesylate—a specific inhibitor of a small family of tyrosine kinases, including Bcr-Abl
TKI Medications Target BCR-ABL CML Survival / “Cure”
Mughal, T. (2016). Chronic Myeloid Leukemia: Reminiscences and Dreams. Hematologica; 101: 541-558.
Chronic Lymphocytic Leukemia
Acute myeloid
AML, APL
Acute lymphoid
ALL
Chronic myeloid
Myeloproliferative
CML
PCV
ET
myelofibrosis
Chronic lymphoid
Lymphoproliferative
CLL/SLL
lymphoma
myeloma
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Chronic Lymphocytic Leukemia
• Usually indolent
5-10 years
• May be best to postpone treatment
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CLL Treatments
Chemotherapy Immunotherapy Biologic Therapy
Cyclophosphamide Rituximab Ibrutinib
Fludarabine Obinatuzimab Idelasilib
Chlorambucil Ofatumamab Develisib
Acute Myeloid Leukemia?
Acute myeloid
AML, APL
Acute lymphoid
ALL
Chronic myeloid
Myeloproliferative
CML
PCV
ET
myelofibrosis
Chronic lymphoid
Lymphoproliferative
CLL/SLL
lymphoma
myeloma
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AML Bad Actors
• Older people >75yo
• FLT3 mutation positive (25%)
• MDS/AML (MDS mutations found)
• Prior cancer (secondary AML)
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What to do When AML is Found
• Assess patient’s ability to be treated– Age, performance status, comorbidities, social factors
• Assess patient’s ability to be cured– Bad actor AML presentations
• Admit/transfer patient to leukemia unit
• Stabilize pt: r/o DIC, infection, bleeding– Don’t miss window to treat AML while waiting for antibiotics to
treat presumed infection
Recent Drug Approvals for AML
• Liposomal daunorubicin/cytarabine• Gemtuzamab: anti-CD33 antibody• Midostaurin: FLT3 inhibitor• Gilteritinib: FLT3 inhibitor• Ivosidenib: IDH1 inhibitor• Enasidenib: IDH2 inhibitor• Venetoclax: BCL2 inhibitor• Glasdegib: Hedgehog inhibitor
APL Leukemia is CurableBUT Deadly if Missed
Lococo, F. et al. (2013). Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia. NEJM 369: 111-121.
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Don’t Miss an APL patient
• Most APL patients are young <50yo• Low WBC (neutropenia) OR high WBC• Any new or abnormal bleeding/bruising• High PTT and low fibrinogen• Can have “spontaneous” intracranial bleeding
• Have high index of suspicion for patients with low plt<50 with bleeding
APL Leukemia Patients
What We do if APL is Suspected
• Start round-the-clock plt and cryo transfusions
• Start empiric tretinoin treatment
• Request FISH for PML-RARa mutation
• If high WBC start hydroxyurea
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What is MDS?
• Abnormal blood counts
• Abnormal bone marrow function
• Clonal stem cell disorder, “pre-leukemia”
• Can cause severe anemia requiring transfusions
• Can cause bleeding requiring transfusions
• Can cause immunocomprimised state
• Can lead to hospitalizations and death
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What MDS Looks Like
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When to Suspect MDS
• Usually hospitalized for “other” things• 15,000 new MDS patients per year in U.S.
• “Community acquired pneumonia”– Why is my patient immunocompromised?
• Anemia assumed a benign problem• Bleeding tendency and bruising may be ignored• Abnormal blood counts should not be ignored
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MDS RBC Dysfunction
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Diagnosis of MDS
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Explaining MDS is an Art
• “What caused me to get this?”• Abnormal counts “missed” or ignored by prior
doctors• “Pre-leukemia” hard to explain and digest• “Bone marrow dysfunction” may be better
understood• Need for chemotherapy means it is like cancer• Decision to treat is not straightforward
– Usually older people with comorbidities– Not curable, so hard to justify aggressive treatment
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Myeloproliferative Disorders
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Blood Disorders Overlap Who Needs a Bone Marrow Biopsy?
• Known or suspected leukemia
• Unexplained low blood counts
• Myeloproliferative disorder (MPD)
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What is Lymphoma?
• Usually lymph nodes and bone marrow
• Systemic disease, may affect any organ
Hodgkin’s
Disease
Non-Hodgkin’s LymphomaDiffuse Large B cell lymphoma
Follicular lymphoma (FL)
Small lymphocytic lymphoma (SLL/CLL)
Mantle cell lymphoma (MCL)
Marginal zone lymphoma (MZL)
T cell lymphoma
Burkitt lymphoma
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NHL Bad Actors
• “Double hit” DLBCL (5%): BCL2/6 & c-myc
• Stage 4 (brain, lungs, bones)
• ABC subtype (Activated B Cell)
• High IPI score (APLES)– Age>60, PS>1, high LDH, extranodal, stage >2
Targeted biologic therapies• Ibrutinib: CLL/SLL, Mantle Cell, Splenic Marginal Zone• Idelalisib: CLL/SLL and Follicular Lymphoma• Acalabrutinib: Mantle Cell Lymphoma• Copanlisib: Relapsed Follicular Lymphoma• Duvelisib: Relapsed CLL/SLL and Follicular Lymphoma
Monoclonal antibodies• Obinutuzimab: CLL and Follicular lymphoma• Brentuximab: Hodgkin’s Lymphoma and T cell lymphoma• Nivolumab: Hodgkin’s Lymphoma after autologous HSCT• Pembrolizumab: Refractory Hodgkin’s Lymphoma
Recent Drug Approvals for Lymphoma
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How Lymphoma is Treated
• Indolent lymphoma may be “observed”
• Chemotherapy/immunotherapy – Rituximab (B cell)
– Brentuximab (T cell)
• Radiation therapy for big tumors or stage 1-2
• Autologous stem cell transplant
• Radioimmunotherapy
• CAR-T immunotherapy
Immunotherapy: CAR-T
The Car T cell revolution: What does it offer, and can we afford it? Cancerworld January, 2018.
What is Multiple Myeloma?
• Means something different to each MM patient• A “blood cancer” like leukemia• A “bone cancer” like leukemia/lymphoma• “Too much protein” in the blood• Sometimes aggressive disease treated by crisis
prevention and management• Sometimes chronic disease treated by cautious
use of anti-myeloma therapy
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Sarah Newbury…the First Known Multiple Myeloma Patient 1844
Kyle, R. (2000). Multiple Myeloma: An Odyssey of Discovery. British Hournal of Hematology, 111, 1035-44
Monoclonal Plasma Cells Secrete Monoclonal “M” Protein
Henry Bence Jones: Bone Fracturesand Abnormal Urine Protein
https://en.wikipedia.org/wiki/Henry_Bence_Jones
Light Chain Deposition Disease
Korngold and Lapiri 1956
Why it’s Called Multiple Myeloma
• Bone tumors throughout the skeleton
• Can be “missed” by a bone biopsy
• Confusing because many patients don’t have actual bone tumors– Diffuse bone infiltration
– Soft tissue variants
– Light chain deposition dz
– Systemic amyloidosis
Explaining Myeloma is an Art
• Variable presentation, tempo, sequelae
• Sometimes young, healthy people
• Always a shock to patients and families
• Sometimes “missed” by prior doctors/ER’s
• Usually several weeks/months of symptoms
• Diagnosis usually made during a crisis
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Myeloma is a Systemic Disease
CRAB Symptoms:
HyperCalcemiaRenal FailureAnemiaBone Tumor/Fracture
Bone Pain May be the Initial Crisis
• Severe bone pain is common– Fracture without trauma = pathologic fracture
– Lytic bone lesions without fracture
– Back pain: r/o spinal cord compression
• Bone pain hurts only while moving, so patients will stay still and become immobile
• Usually myeloma patients are older people who fear becoming addicted to opiate meds
Recent Drug Approvals for Multiple Myeloma
• Pomalidomide (oral) biologic therapy
• Carfilzomib (IV) chemotherapy
• Elotuzamab (IV) immunotherapy
• Daratumamab (IV) immunotherapy
• Ixazomib (oral) chemotherapy
• Selinexor (oral) biologic therapy
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Take Home Messages
• Blood cancers account for 10% of new cancer– Leukemia, lymphoma, and multiple myeloma
• Abnormal “screening” CBC should trigger testing– WBC Differential, fibrinogen, flow cytometry, SPEP
• Multiple myeloma is a blood cancer that affects each patient differently, usually starts with a crisis
• Blood cancer patients who are not cured need expert palliative care to live longer and better
References
• Acute Myeloid Leukemia review– NEJM 9/17/15; 373: 1136-1152.
• Adult Primary Care after Childhood ALL– NEJM 10/13/11; 365:1417-1424