Multiple Myeloma Case studies UKMF Education Day November 2011 Kwee Yong Cancer Institute University...
-
Upload
maximilian-mason -
Category
Documents
-
view
214 -
download
1
Transcript of 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
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 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
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 Dexamethasone3. ESHAP with PBSCH4. Proceed to allogeneic transplant
Case 1: Lynne
What would you do now?
Case 1: Decision point 4
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
What would you do now?
Case 1: Decision point 5
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
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
• 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
What would you do now?
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
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
What would you do now?
Case 3: Decision point 2
• 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
What would you do now?
FISH: t(11;14) single fusionTP53: deleted in 88%
BM
Case 4: Decision point 2
1.Add Cyclophosphamide to Revlimid /Dex2.Proceed with mobilising stem cells3.ESHAP-type regimen 4.Palliate
Case 4: Michael
What would you do now?
Case 4: Decision point 3
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
?
Case 5: Decision point 1
1. Palliate2. Cyclophosphamide and
dexamethasone3. Thalidomide regimen4. Re-treat with velcade on NHS
Case 5: John
Case 5: Decision point 2
• 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