case presentation ‘nurse and doc’€¦ · multiple myeloma al amyloidosis r ca2+ anemia c a b...

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

- > 1 focal lesion on MRI (> 5mm)Do not duplicate or d

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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

MDEDo not duplicate or d

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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

High risk GEPprofileDo not duplicate or d

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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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case presentation ‘nurse and doc’€¦ · multiple myeloma al amyloidosis r ca2+ anemia c a b...

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