case presentation ‘nurse and doc’€¦ · multiple myeloma al amyloidosis r ca2+ anemia c a b...
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Case presentation‘nurse and doc’
Stef Meers,MD,PhD
Johan De Munter, RN
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Disclosures
• No relevant conflicts of interest to disclose
• These slides may discuss combinations of drugs not licensed in every country of EU
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Case
• 67y old female
- Past medical history
◦ Arterial hypertension
- “abnormal protein electrophoresis” & back pain
- Lab
◦ Hb 8,2g/dL
◦ Creatinine 1.51 mg/dL
◦ Albumine 36g/L
◦ IgG 64g/L, M-spike 56g/L
◦ sFLC: k 6,24mg/L // l 5460mg/L
◦ Calcium 3.2mmol/L
◦ Urine: proteinuria 3.4g/24h
◦ Beta2-microglobuline 4.2 mg/L
Nursing intervention:comprehensive assessment & extensive pain assessment
Presumably also other symptomatology such as fatigue, lowered QoL and stress (or anxiety).
Nursing intervention:Assessment of nutritional statusRefer to dietition if necessary
Kidney function assessment24h urine collectionAdvise to drinkBlood pressure self assessmentObservation of urineDo not duplica
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Case
• 67y old female
- Bone marrow
◦ 39% plasmacells, monoclonal lambda
◦ FISH: hyperploidy, T(11;14), +1q
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Questions
• Is this a multiple myeloma?
• Does this patient require treatment?
• “How long do I have, doc?”
• Treatment options
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Multiple myeloma: epidemiology
• 1% of all cancers, 10% of hematologic malignancies
• Incidence 4/100.000/y in US
• M/F (2/1)
• Median age at diagnosis 65y, 25% > 75y
- 3% < 40j, 18% < 50j
• Very variable O.S. : 1-10y
Nursing intervention:G8 (GERIATRIC 8) HEALTH STATUS SCREENING TOOL
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Pathogenesis
Too many plasmacells Antibody deposition
Multiple myeloma AL amyloidosis
R
Ca2+ Anemia
AC Brenal
neuropathy
cardiac
organomegaly
skin
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Pathogenesis
Too many plasmacells Antibody deposition
Multiple myeloma AL amyloidosis
R
Ca2+ Anemia
AC Brenal
neuropathy
cardiac
organomegaly
skin
Nursing intervention:
Hypercalcaemia paraneoplastic condition that is associated with many forms of cancer
→ particularly severe in myeloma because of the increased bone turnover.
➔medical emergency!
Nursing intervention: Renal impairment
→ affects up to half of all patients with myeloma at some stage in their illness.
→ consequence of paraproteinemia causing proximal tubular damage or to protein cast nephropathy
→ possible other causes → hypercalcemia, dehydration,
hyperuricemia, infection or the action of nephrotoxic drugs!
Nursing intervention: Anemia
Hb 8,2g/dL = moderate anemia (NCI-CTCAE V4.03 Anemia scale)
→ Neg influence on QoL
→ contributes to cancer-inducedfatigue
Nursing intervention: Following up pain symptoms
Myeloma bone damage may lead to pathological fractures in long bones & to vertebral collapse
→ increased risk of developing (Spinal Cord Compression) (Tosi, 2013). = medical emergency!
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International Myeloma Working GroupIMWG criteria 2014
MULTIPLE MYELOMA
Presence of ≥ 10% clonal plasmacells or biopsy showingplasmacytoma (bone or extramedullary)
AND
Presence of “myeloma-defining event”Do not duplicate or d
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Myeloma defining events
“CRAB”- C: Calcium > 11.0 mg/dL (or +1mg/dL > ULN)
- R: serum creatinine > 2 mg/dL (or crcl < 40mL/min)
- A: Hb < 10g/dL or Hb < 2g/dL
- B: 1 or more osteolytic lesions on RX, CT, PET/CT
Other myeloma-defining events (MDE)- ≥ 60% clonal plasmacells in BM
- sFLC ratio ≥ 100 with kappa or lambda > 100mg/L
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Differential diagnosis of plasmacell disorders
MGUSSmoldering
MM
Multiple myeloma
MGUS SMM MM
M-spike < 30g/L ≥ 30g/L
% clonal plasmacells
< 10 10 – 60 ≥ 10 or biopsy
Organ damage? no MDE or amyloidosis
no MDE or amyloidosis
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“How long do I have doc?”
<65y
>65y
Kumar et al Leukemia 2014
Trends in surival
Heterogenous!
Disease aggressiveness
Trisomies T(11;14) (CCND1)T(6;14) (CCND3)
T(4;14) (FGFR3,MMSET)T(14;16) (C-MAF)T(14;20) (MAF-B)
Kumar et al. Blood 2012
Multiple “multiple myelomas”
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“How long do I have doc?”
Host Genetics Other factors
Age Hypodiploidy % S phase
ECOG Del(17P) Circulatingplasmacells
Comorbidity T(4;14)T(14;16) T(14;20)
High sFLC ratio
Del (1P) Extramedullary disease
Add (1Q) Rapid relapse
Del (13Q) Less residual polyclonalplasmacells
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ISS & Revised-ISS
Stage Serum beta2-microglobulin
Albumin O.S.(mths)
I < 3,5 mg/L ≥ 35 g/L 62
II Not stage I or III 44
III ≥ 3,5 mg/L 29
Stage
I ISS st I + standard risk CG + nl LDH
II No R-ISS st I or III
III ISS st III +/- high risk CG +/- high LDH
JCO 2005;23:3412-3420
Revised-ISS
High risk CG* Del (17P), T(4;14); T(14;16)
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Risk stratification
High-Risk Myeloma Standard-Risk Myeloma
FISH• T(4;14)• T(14;16)• T(14;20)• Del 17p• 1q gainDouble-Hit Myeloma = any 2 high risk abnormalitiesTriple-Hit Myeloma = 3 or more high risk abnormalities
All others including
• Trisomies• T(11;14)• T(6;14)
mSMART 3.0: Risk Stratification of Active MM
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“How long do I have, doc?”
• “Very hard to say, dear patient”
• Inconvenient truth: incurable…
Nursing intervention:Stress and/or anxietyInduce advanced care planning?
Emotional support to patient & relatives
Importance: Overall health maintenance, bone health →mobility & safety, renal health, reduce anemia, reduce infections, …
Communication to Family doctor, nursing home
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Our patient
• 67y old female
- Lab◦ Hb 8,2g/dL
◦ Creatinine 1.51 mg/dL
◦ Albumine 36g/L
◦ IgG 64g/L, M-spike 56g/L
◦ sFLC: k 6,24mg/L // l 5460mg/L
◦ Calcium 3.2mmol/L
◦ Urine: proteinuria 3.4g/24h
◦ Beta2-microglobuline 4.2 mg/L
- Bone marrow◦ 39% plasmacells, monoclonal lambda
◦ FISH: hyperploidy, T(11;14), +1q
• MM? - Y: 39% plasmacells + anemia
• Treatment- Y: backpain
• “How long do I have?”- R-ISS
◦ Stage III because ISS stage III
◦ (! +1q is high risk, but not in R-ISS)Do not duplicate or d
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Treatment
First line treatment Bone directed treatment
Prevention of infections
PATIENT
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Bone directed treatment
• At diagnosis, up to 90% of patients have detectable bone lesions
• Increased bone resorption vs. Decreased bone formation→ LYTIC lesions + Hypercalcemia
• Skeletal-related events - Pathological fractures
- Surgery of radiotherapy to bone
- Spinal cord compression
Morgan et al. MRC IX trial. Clin Cancer Res 2013 Raje et al. Lancet Oncol 2018;19:370
Zoledronic acid denosumab
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Bone directed treatment
Nursing observation:Pain! Muscle weakness,
sensory loss,parasthesia
bladder dysfunctionataxia
If ambulatory→ ability to walk!
Nursing observation:muscle weakness
vague abdominal painconstipation, anorexia, increased
thirst, frequent urinationconfusion, disorientation, and difficulty thinking, headaches,
depression & fatigue
HYPERCALCEMIALYTIC BONE LESIONSDo not duplicate or d
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Infections
• Hypogammaglobulinemia
- @ risk for encapsulated bacteria
- S.pneumoniae, H.influenzae
- R/ Vaccination, IVIg
• Neutropenia- IMID’s
• Influenza
• P.jiroveci pneumonia
- Steroids
- R/ co-trimoxazole
• Varicella zoster infections, HSV
- Proteasome inhibitors
Nursing intervention:
Vaccination statusRisk assessment of neutropenia
Steroids & risk for infections
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Therapeutic agents
ALKYLATING AGENTS
Melphalan
Cyclophosphamide
Bendamustine
IMID’s
Thalidomide
Lenalidomide
Pomalidomide
PROTEASOME
INHIBITORS
Bortezomib
Carfilzomib
Ixazomib
“CHEMO”
(Liposomal) doxorubicin
Cisplatinum
Etoposide
STEROIDS
Dexamethasone
Prednisone
Methylprednisolone
ANTIBODIES
Daratumumab
Elotuzumab
HDAC
INHIBITORS
Panabinostat
CAR T CELL
BCMA
CD38
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Frontline treatment: fit patients
Remission-induction
Stemcell-mobilisation
Tx
Post-transplant-consolidation-maintenance
MEL
200m
g/m
2
CD
34+
rein
fusi
on
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Front line treatment: unfit patients
Fixed number of cycles
• Velcade-based
- VMP (Velcade-melphalan-prednisone)
- VCD (Velcade-cyclophosphamide-dex)
- VRD (Velcade-Revlimid-dexamethasone)
• Thalidomide-based
- MPT (melphalan-prednisone-thalidomide)
- CTD (cyclophosphamide-thalidomide-dex)
• Alkylator+steroid
- Bendamustine – prednisone
- MP (melphalan – prednison)
Continuous treatment
• Revlimid-based
- Revlimid-dexamethasone (Rd)
- Revlimid maintenance after MP-R
- Revlimid maintenance after VRD
Benboubker et al, NEJM, 2014
FIRST
Durie et al. The Lancet 2017
SWOG S0777
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Front line treatment
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Our patient
• 67y old, no significant comorbidities
→VTD induction and autologous stemcell transplantation
Nursing:Dental examination
Corticoïd related side effects!!
Assessment PN:History, reflex status, sensory
& motor function & Functionalimpairment
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Our patient
• Cycle 3d7 admitted to ER
- Chest pain and dyspnoea
- temp 37.9°C
- adequate BP
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Chest pain in MM patient: differential
PULMONARY EMBOLISM
- MGUS/MM trombogenic stateHR 3.4 (venous) HR 1.7 (arterial)(Kristinsson et al Blood 2010)
- IMID’s trombogenic
SKELETAL PAIN
HERPES ZOSTER (SHINGLES)
PNEUMONIA
- Hypogammaglobulinemia@risk for S.pneumoniae
- steroids--> P.jiroveci pneumonia
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Our patient
• Cycle 4 d4
- Progressive weakness thighs
- Difficulties getting up from chair
- Ankle oedema
STEROID MYOPATHY
DVT
POLYNEUROPATHY
ION DISTURBANCES DIABETES
Steriods: the necessary evil
can affect the immune, musculoskeletal, and endocrine systems, the skin, the heart and blood pressure, the gastrointestinal tract, and the eyes. CAVE: can cause psychological problems, affecting cognition, mood, and behavior.
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Polyneuropathy
Confirming neuropathy• nerve conduction test (NCS)• electromyography (EMG)
Available at: https://www.nhs.uk/conditions/peripheral-neuropathy/symptoms/ (Last accessed: 02.22.18).
Comorbidities are also associatedwith PN:• Diabetes mellitus• Metabolic & endocrine
diseases• Vitamin deficiency (VitB12)
Alcohol abuse• Viral infections (e.g. VZV)
“unpleasant tingling sensation in the feet
and hands”
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Our patient
Remission-induction
Stemcell-mobilisation
Tx
Post-transplant-consolidation-maintenance
MEL
20
0m
g/m
2
1 /
The autologous stem cell transplant
Mobilization
Collection
Conditioning
Stem cell reinfusion
Follow-up
Processing
& Freeze
= with stem cells from the patient himself!
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Autologous transplantation
• Before novel agents→ autologous tx about 12 mths OS benefit
• Era of novel agents→PFS benefit
→OS benefit?
Attal et al. NEJM 2017
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Maintenance
• Lenalidomide
Meta-analysis (McCarthy et al. JCO 2017)
◦ median PFS 52.8 months vs. 23.5 months for the placebo or observation group(HR 0.48; 95% CI, 0.41 to 0.55)
◦ O.S. NR vs. 86.0 months for the placebo or observation group(HR 0.75; 95% CI, 0.63 to 0.90; P = .001)
◦ Secondary cancers 7% vs. 2.6%
• Bortezomib◦ High risk (Sonneveld et al. JCO 2012)Do not duplica
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The story continues
• Diagnosis- M-spike 56g/L
• After induction- M-spike 15g/L (PR)
• After MEL 200mg/m²- M-spike 3g/L (VGPR)
• After 2y of LEN maintenance- M-spike 2g/L (VGPR)
• 15 months later- M-spike 5g/L
• 17 months later- M-spike 8g/L
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Treatment of R/R multiple myeloma
ALKYLATING AGENTS
Melphalan
Cyclophosphamide
Bendamustine
IMID’s
Thalidomide
Lenalidomide
Pomalidomide
PROTEASOME
INHIBITORS
Bortezomib
Carfilzomib
Ixazomib
“CHEMO”
(Liposomal) doxorubicin
Cisplatinum
Etoposide
STEROIDS
Dexamethasone
Prednisone
Methylprednisolone
ANTIBODIES
Daratumumab
Elotuzumab
HDAC
INHIBITORS
Panabinostat
CAR T CELL
BCMA
CD38
Triplet: Revlimid as backbone Carfilzomib-Revlimid-Dexamethasone (KRd)Daratumumab-Revlimid-Dexamethasone (DRd) Ixazomib-Revlimid-Dexamethasone (IRd)Elotuzumab-Revlimid-Dexamethasone (EloRd)
Triplet: Velcade as backboneVelcade-Cyclofosfamide-Dexamethasone (VCD)Velcade-Dexamethasone-CaelyxDaratumumab-Velcade-Dexamethasone (DVd)Panobinostat-Velcade-Dexamethasone
Triplet: Pomalidomide as backbonePomalidomide-Cyclofosfamide-Dexamethasone (PomCycloDex)Elotuzumab-Pomalidomide-Dexamethasone
DoubletRevlimid-dexamethasone (Rd)Pomalidomide-dexamethasone (Pd)Velcade-dexamethasone (Vd)Thalidomide-dexamethasone (Td)
MonotherapyDaratumumab
Intensive chemoDCEP, DT-PACE
…
Depends on:AgePerformance statusComorbiditiesPrevious treatment
EfficacyTolerance
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ESMO guidelines
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Advance Care Planning & palliative care integration for hematological patients
37 /
Advance Care Planning and Palliative Care Integration for Patients Undergoing
Hematopoietic Stem-Cell Transplantation. J Oncol Pract. 2017 Sep;13(9):e721-e728. doi:
10.1200/JOP.2016.020321. Epub 2017 Jun 23
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Time for questions
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