multiple myeloma case studies ukmf education day november 2011 kwee yong cancer institute university...
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Multiple Myeloma Case studiesUKMF Education Day November 2011
Kwee YongCancer Institute
University College London
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Case 1 : Lynne
• 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
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Several karytopic abnormalities
Case 1: Lynne
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• July 2010: CTD & zometa (sibling match)– Neutropenia after one dose Cyclo– Thal/Dex– Poor tolerance: dizziness, bradycardia (45-50/min)– Pp 46, then 53
Case 1: Lynne
What would you do now?
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Case 1: Decision point 1
1. Continue with Dexamethasone alone2. Switch to Velcade and Dexamethasone3. Continue with Cyclophosphamide and
dexamethasone with growth factor support4. Stop treatment to allow bone marrow
recovery
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• July 2010: CTD & zometa (sibling match)– Neutropenia after one dose Cyclo– Thal/Dex– Poor tolerance: dizziness, bradycardia (45-50/min)– Pp 46, then 53
Case 1: Lynne
August 2010: Velcade/Dex3 cyclesStable diseaseGrade 1 PN
What would you do now?
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Case 1: Decision point 2
1. Continue with Velcade and Dexamethasone for further 2-3 cycles as tolerated
2. Switch to Revlimid and Dexamethasone3. Add Revlimid to Velcade and Dexamethasone4. Arrange mobilisation and PBSCH
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• Revlimid 10mg od days 1-14, with velcade 1.3g/m2 and dex
• After 14 days, neutrophils 0.6• Prolonged neutropenia• Transfusions
Case 1 : Lynne
What would you do now?
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Case 1: Decision point 3
1. Wait for bone marrow recovery and try again with RVD
2. Switch to Revlimid and Dexamethasone3. ESHAP with PBSCH4. Proceed to allogeneic transplant
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Case 1: Lynne
What would you do now?
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Case 1: Decision point 4
1. Salvage regimen prior to ASCT2. Proceed to allogeneic transplant3. Proceed to ASCT4. Clinical trial of new agent
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ASCT
• 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
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Case 1: Lynne
BM 3% PCVGPR
What would you do now?
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Case 1: Decision point 5
1. Nothing2. Reduced intensity sibling allograft (LenaRIC
study)3. Maintenance with lenalidomide4. Maintenance with thalidomide
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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
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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
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R L
Case 2: Joanna
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• Immune paresis• Urine protein: 2g/24 hr• SFLC: kappa 4720mg/L• BMT: 80% plasma cells, cyclin D1+, CD56-• FISH: IgH split, 17p loss in all cells• CT-PET: FDG avid lesions manubrium, • R iliac bone, R base of skull, T5
Case 2: Joanna
Case 2: Joanna
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Case 2 : Decision point 1How would you manage this patient?
1. Urgent DXT to base of skull2. Treat with CTD3. Use high grade NHL protocol with CNS
treatment4. Velcade and dexamethasone
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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 1: JoannaCase 2: Joanna
Case 2: Joanna
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• 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
Case 2: Joanna
What would you do now?
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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
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• 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: Joanna
Case 2: Joanna
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Case 2: repeat imaging
What would you do now?
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Case 2: Decision point 3
1. Consolidation DXT to base of skull2. Do nothing3. Maintenance with thalidomide
(lenalidomide)4. Search for donor (MUD RIC-allo, -LenaRIC?)
Case 2: Joanna
30 Gy DXT to base of skull in 15 fractionsWatch and wait
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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
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Case 3: Lenny
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Case 3: Lenny
MRI: extensive paravertebral mass T11-L2, extending into soft tissues, and into the spinal canal at L1 compressing the conusBiopsy at Stanmore: Plasma cell tumour
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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: LennyCase 3: Lenny
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Case 3: Decision point 1How would you manage this patient?
• Surgery and decompression• Radiotherapy• Treat with CTD• Treat with velcade and
dexamethasone
Case 3: Lenny
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• 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: LennyCase 3: Lenny
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• 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
Case 3: Lenny
What would you do now?
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Case 3: Decision point 2
• Stop CVD and give radical DXT• Continue with CVD • Switch to CTD• Surgery to stabilise spine
Case 3: Lenny
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Spinal plasmacytoma:Radiotherapy, surgical decompression/fixation
or systemic treatment?
• Level of tumour– Cervical, thoracic, T-L jn, lumbo-sacral
• Spinal cord issues: bony or tumour
• Spinal stability: (bracing?)
• Presence of disease elsewhere• Stage of disease (diagnosis, relapse)
• Access (clinical oncologists, surgical colleagues)
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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
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• 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• 2microglobulin 9.3mg/L• SFLC lambda 5270mg/L• Calcium and Renal function normal
Case 4: Michael
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• 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: Michael
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Case 4: Decision point 1How would you treat this patient?
1.CTD2.Velcade and dexamethasone3.Urgent radiotherapy to paravertebral mass4.VAD/Idarubicin & Dex
(Myeloma XI, PADIMAC)
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Case 4: Michael
What would you do now?
FISH: t(11;14) single fusionTP53: deleted in 88%
BM
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Case 4: Decision point 2
1.Add Cyclophosphamide to Revlimid /Dex2.Proceed with mobilising stem cells3.ESHAP-type regimen 4.Palliate
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Case 4: Michael
What would you do now?
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Case 4: Decision point 3
1. Do nothing2. Search for donor for RIC allo 3. Maintenance with thalidomide4. Consolidation - ?
VTD consolidation
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VAD TD VD RD TAD PAD VTD
Summary of novel agent induction trials (randomized studies)
Post-inductionPost-transplant
≥ VGPR rates post-induction and post-transplant
Harousseau et al. ASH/ASCO symposium during ASH 2008Rajkumar et al. ASCO 2008 (Abstract 8504); ASH/ASCO symposium during ASH 2008
Lokhorst et al. Haematologica 2008;93:124–7Sonneveld et al. ASH 2008 (abstract 653); IMW (abstract 152) Cavo et al. ASH 2008 (abstract 158); IMW 2009 (abstract 451)
*Post-transplant data not available
15-16%
30-35%
39% 33% 45%62%
42%
44-50%45-55%
57%49%
71%
79%
*
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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
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(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).
Avet-Loiseau H et al. JCO 2010;28:4630-4634©2010 by American Society of Clinical Oncology
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Case 5: John
• 63 year old aircraft engineer• Presented with anaemia • Diagnosed with IgGk MM• Initial treatment with VAMP, minor response• CDT x 5• ASCT
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Case 5: John
?
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Case 5: Decision point 1
1. Palliate2. Cyclophosphamide and
dexamethasone3. Thalidomide regimen4. Re-treat with velcade on NHS
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Case 5: John
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Case 5: Decision point 2
• Palliate• Thalidomide• Cyclophosphamide and dexamethasone• Clinical trial
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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
• Other, eg carfilzomib