multiple myeloma case studies ukmf education day november 2011 kwee yong cancer institute university...

Multiple Myeloma Case studiesUKMF Education Day November 2011

Kwee YongCancer Institute

University College London

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

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

Case 1: Lynne

What would you do now?

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

• 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



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

• 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



1. Wait for bone marrow recovery and try again with RVD

2. Switch to Revlimid and Dexamethasone3. ESHAP with PBSCH4. Proceed to allogeneic transplant

Case 1: Lynne



1. Salvage regimen prior to ASCT2. Proceed to allogeneic transplant3. Proceed to ASCT4. Clinical trial of new agent

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

Case 1: Lynne

BM 3% PCVGPR



1. Nothing2. Reduced intensity sibling allograft (LenaRIC

study)3. Maintenance with lenalidomide4. 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

R L

Case 2: Joanna

• 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

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

• 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

• 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

• 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



• Assume liver lesions disease and treat with Revlimid and dexamethasone

• Attempt further biopsy of liver• Continue posaconazole and re-scan• Proceed with ASCT

• 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

Case 2: repeat imaging



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

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

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

• 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

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

• 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

• 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



• Stop CVD and give radical DXT• Continue with CVD • Switch to CTD• Surgery to stabilise spine

Case 3: Lenny

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)

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

• 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

• 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

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)

Case 4: Michael


FISH: t(11;14) single fusionTP53: deleted in 88%

BM


1.Add Cyclophosphamide to Revlimid /Dex2.Proceed with mobilising stem cells3.ESHAP-type regimen 4.Palliate

Case 4: Michael



1. Do nothing2. Search for donor for RIC allo 3. Maintenance with thalidomide4. Consolidation - ?

VTD consolidation

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%

*

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).

Avet-Loiseau H et al. JCO 2010;28:4630-4634©2010 by American Society of Clinical Oncology

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

Case 5: John

?


1. Palliate2. Cyclophosphamide and

dexamethasone3. Thalidomide regimen4. Re-treat with velcade on NHS

Case 5: John


• 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

• Other, eg carfilzomib

multiple myeloma case studies ukmf education day november 2011 kwee yong cancer institute university...

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