Multiple Myeloma Case studies
UKMF Education Day November 2011
Kwee Yong
Cancer Institute
University College London
Case 1 : Lynne
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36 year old business manager
June 2010: fatigue & nosebleeds
Hb 8.8g/dL, WBC 2.8 x 109/L, Neuts 0.9, plts 198
IgG 79g/L, pp = 61
Creatinine 109umol/L, normal Ca++
Albumin 33g/L, b2m 3.7mg/L (ISS Stage 2)
BMT: 80% plasma cells, CD56+, cyclin D1+
FISH: t(11;14)
SS: no lytic lesions, MRI spine: no focal lesions
Case 1: Lynne
Several karytopic abnormalities
Case 1: Lynne
• July 2010: CTD & zometa (sibling match)
– Neutropenia after one dose Cyclo
– Thal/Dex
– Poor tolerance: dizziness, bradycardia (45-50/min)
– Pp 46, then 53
What would you do now?
Case 1: Decision point 1
1. Continue with Dexamethasone alone
2. Switch to Velcade and Dexamethasone
3. Continue with Cyclophosphamide and
dexamethasone with growth factor support
4. Stop treatment to allow bone marrow
recovery
Case 1: Lynne
• July 2010: CTD & zometa (sibling match)
– Neutropenia after one dose Cyclo
– Thal/Dex
– Poor tolerance: dizziness, bradycardia (45-50/min)
– Pp 46, then 53
August 2010: Velcade/Dex
3 cycles
Stable disease
Grade 1 PN
What would you do now?
Case 1: Decision point 2
1. Continue with Velcade and Dexamethasone
for further 2-3 cycles as tolerated
2. Switch to Revlimid and Dexamethasone
3. Add Revlimid to Velcade and Dexamethasone
4. Arrange mobilisation and PBSCH
Case 1 : Lynne
• Revlimid 10mg od days 1-14, with velcade
1.3g/m2 and dex
• After 14 days, neutrophils 0.6
• Prolonged neutropenia
• Transfusions
What would you do now?
Case 1: Decision point 3
1. Wait for bone marrow recovery and try again
with RVD
2. Switch to Revlimid and Dexamethasone
3. ESHAP with PBSCH
4. Proceed to allogeneic transplant
Case 1: Lynne
What would you do now?
Case 1: Decision point 4
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Salvage regimen prior to ASCT
Proceed to allogeneic transplant
Proceed to ASCT
Clinical trial of new agent
Case 1: Lynne
ASCT
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Jan 2011 (27 weeks after diagnosis): pp 42
ASCT 14.01.2011
5 week admission
Fever day -1
Grade 3/4 mucositis: diarrhoea++, nausea,
dehydrated
• Hypokalaemia induced DI: polyuria, polydipsia
• Neut engraftment day +12
• Discharged day +33
Case 1: Lynne
BM 3% PC
VGPR
What would you do now?
Case 1: Decision point 5
1. Nothing
2. Reduced intensity sibling allograft (LenaRIC
study)
3. Maintenance with lenalidomide
4. Maintenance with thalidomide
Case 1: issues
• Primary refractory MM
• Discordance in prognostic information
between FISH and karyotype
• Sibling match – when to allograft?
• Case for tandem sib RIC allo?
• Poor tolerance of chemotherapy
• Toxicity of conditioning
Case 2: Joanna
• 49 year old charity worker
• June 2010
– ‘blocked ear’ for 2 mo
– Sudden onset diplopia and numbness R face 4 days
• Right 6th nerve palsy
• MRI head: large irregular tumour arising from clivus
and R sphenoid, invading cavernous sinus
• CT scan: rib lesions, T5 lesion invading canal, large
sacral mass, sternal mass, L iliac lesion, breast lump
Case 2: Joanna
R
L
Case 2: Joanna
Case 2: Joanna
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Immune paresis
Urine protein: 2g/24 hr
SFLC: kappa 4720mg/L
BMT: 80% plasma cells, cyclin D1+, CD56FISH: IgH split, 17p loss in all cells
CT-PET: FDG avid lesions manubrium,
R iliac bone, R base of skull, T5
Case 2 : Decision point 1
How would you manage this patient?
1. Urgent DXT to base of skull
2. Treat with CTD
3. Use high grade NHL protocol with CNS
treatment
4. Velcade and dexamethasone
Case 2:
1: Joanna
Case 2: Joanna
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LP: no cells, methotrexate
High dose dexamethasone
Velcade, Idarubicin & Ara-C (June 2010)
Clinical response, MRI improvement, KLC
79mg/L
• July 2010: Ida-Ara-C no.2 with Velcade/dex
– Neutropenic fever, klebsiella septicaemia
– Hypoxia, severe mucositis
Case 2: Joanna
• Velcade / dexamethasone no.3
• Re-staging MRI: good response to treatment
• PET-CT scan: new FDG-avid lesions in liver and
spleen, previous lesions resolved
• BM: CR, KLC 1.7mg/L, urine: IF neg for BJP
Case 2: Joanna
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Biopsy liver lesions x 3!!
Fibrosis with inflammatory cells
Rx: posaconazole 3 mo
Velcade / Dexamethasone no.4
Cyclo-G-CSF prime and PBSC harvest
Repeat CT scan: lesions unchanged
What would you do now?
Case 2: Decision point 2
• Assume liver lesions disease and
treat with Revlimid and
dexamethasone
• Attempt further biopsy of liver
• Continue posaconazole and re-scan
• Proceed with ASCT
Case 2: Joanna
Case 2: Joanna
• 25 Feb 2011: Melphalan 140 / TBI
– 12 Gy in 6 fractions
• ASCT in ambulatory care
• Fever day +8, resistant E Coli, PICC line out
• Engrafted day +12, discharged day +15
• May 2011: BM clear, SFLC normal,
– CT abdo: lesions smaller
– MRI head
Case 2: repeat imaging
What would you do now?
Case 2: Joanna
Case 2: Decision point 3
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Consolidation DXT to base of skull
Do nothing
Maintenance with thalidomide
(lenalidomide)
Search for donor (MUD RIC-allo, -LenaRIC?)
30 Gy DXT to base of skull in 15 fractions
Watch and wait
Case 3: Lenny
Case 3: Lenny
• 45 yr old warehouse supervisor
• Aug 2011: Back pain since Dec 2010
– Anorexia and weight loss
– Unsteady walking
– “Numb balls”
– Sluggish bowels, urinary hesitancy
– Pain radiating down legs, walking with sticks
Case 3: Lenny
Case 3: Lenny
MRI: extensive paravertebral mass T11-L2, extending into soft tissues,
and into the spinal canal at L1 compressing the conus
Biopsy at Stanmore: Plasma cell tumour
Case 3: Lenny
Case 3: Lenny
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Dexamethasone 4mg qds
BM clear
FBC normal, renal function normal
SEP small IgAk pp, total IgA 9.8g/L
SFLC
SS, MRI spine: no other lesions
Solitary plasmacytoma
Case 3: Decision point 1
How would you manage this patient?
Case 3: Lenny
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Surgery and decompression
Radiotherapy
Treat with CTD
Treat with velcade and
dexamethasone
Case 3: Lenny
Case 3: Lenny
• Velcade, cyclophosphamide & dexamethasone
started within 24 hours
• Radiotherapy review – on hold
• Pain decreased, improved mobility
• Postural drop beginning of cycle 2
– Lying 130/75, standing 107/70
– asymptomatic
• Delay 1 week
Case 3: Lenny
• MRI after 2 cycles CVD, marked improvement
• Sensation in groins now normal, perineal
parasthesiae persists but better
• Bowels : grade 1 constipation
• Bladder function normal
• IgA reduced from 9.8 to 1.7g/L
What would you do now?
Case 3: Lenny
Case 3: Decision point 2
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Stop CVD and give radical DXT
Continue with CVD
Switch to CTD
Surgery to stabilise spine
Spinal plasmacytoma:
Radiotherapy, surgical decompression/fixation
or systemic treatment?
• Level of tumour
– Cervical, thoracic, T-L jn, lumbo-sacral
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Spinal cord issues: bony or tumour
Spinal stability: (bracing?)
Presence of disease elsewhere
Stage of disease (diagnosis, relapse)
Access (clinical oncologists, surgical colleagues)
Solitary bone plasmacytoma
• Most (>70%) progress to MM, majority within
2-4 years
• Risk of progression assoc with persistence of
M-band, abnormal SFLC ratio
• PET-CT scanning may be useful to identify
occult disease
• Relatively indolent disease even after
progression, OS 5-10 years
Case 4: Michael
• 55 yr old schoolteacher
• March 2010: back pain (previous L4/5
vertebrectomy)
• Hb 6.6g/dl, WBC 2.4, neuts 1.2, Plats 34
• SEP: pp 2 g/L, UTP 9 g/L
• b2microglobulin 9.3mg/L
• SFLC lambda 5270mg/L
• Calcium and Renal function normal
Case 4: Michael
• BM 90% cyclin D1+ PC, FISH ? Partial p53 loss
• MRI: diffuse abn BM signal, extraosseus
tumour left 6th rib, paravertebral mass at
T11/12
• No spinal cord issues, neurologically intact
Case 4: Decision point 1
How would you treat this patient?
1. CTD
2. Velcade and dexamethasone
3. Urgent radiotherapy to paravertebral
mass
4. VAD/Idarubicin & Dex
(Myeloma XI, PADIMAC)
Case 4: Michael
BM
FISH: t(11;14) single fusion
TP53: deleted in 88%
What would you do now?
Case 4: Decision point 2
1. Add Cyclophosphamide to Revlimid
/Dex
2. Proceed with mobilising stem cells
3. ESHAP-type regimen
4. Palliate
Case 4: Michael
What would you do now?
Case 4: Decision point 3
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Do nothing
Search for donor for RIC allo
Maintenance with thalidomide
Consolidation - ?
VTD consolidation
Summary of novel agent induction
trials (randomized studies)
≥ VGPR rates post-induction and post-transplant
Post-induction
Post-transplant
79%
71%
57%
44-50%
45-55%
49%
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1516%
3035%
VAD
TD
42%
62%
33%
45%
VD
RDnot available
TAD
*Post-transplant
data
PAD
39%
Harousseau et al. ASH/ASCO symposium during ASH 2008
Rajkumar et al. ASCO 2008 (Abstract 8504);
ASH/ASCO symposium during ASH 2008
VTD
Lokhorst et al. Haematologica 2008;93:124–7
Sonneveld et al. ASH 2008 (abstract 653); IMW (abstract 152)
Cavo et al. ASH 2008 (abstract 158); IMW 2009 (abstract 451)
17p- disease in MM
• 9-10% at presentation
• Progression event
• Associated with Light chain only disease, high
ISS stage
• Prognostic only if in ≥50% plasma cells
• Very poor outlook
• IFM study of Vel/Dex, EFS 14 mo vs 36mo
(A) Event-free survival (EFS) and (B) overall survival (OS) in patients with del(17p) (n = 54) or
without del(17p) (n = 453) treated with bortezomib-dexamethasone induction (EFS and OS in
years; P < .001 for EFS and OS).
©2010 by American Society of Clinical Oncology
Avet-Loiseau H et al. JCO 2010;28:4630-4634
Case 5: John
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63 year old aircraft engineer
Presented with anaemia
Diagnosed with IgGk MM
Initial treatment with VAMP, minor response
CDT x 5
ASCT
Case 5: John
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Case 5: Decision point 1
1. Palliate
2. Cyclophosphamide and
dexamethasone
3. Thalidomide regimen
4. Re-treat with velcade on NHS
Case 5: John
Case 5: Decision point 2
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Palliate
Thalidomide
Cyclophosphamide and dexamethasone
Clinical trial
Clinical trials for relapsed MM
• Bortezomib trials (± HDACi, ±hsp90i,
±mAb)
– Usually IV velcade
– 1-3 prior lines
• Lenalidomide trials (±carfilzomib, ±CS1
mAb)
• Pomalidomide trials
• MUK Clinical Trials Network early phase
studies
– Less restriction in no of prior lines