Multiple Myeloma Flashcards
disease progression
MGUS->smouldering myeloma->intramedullary myeloma->extramedullary myeloma->myeloma cell line
signs and symptoms -2
- CRAB - calcium >11.5, renal dysfunction (SCr >2), anemia (hgb), bone
- presents as HA, blurred vision, epistaxis, oral bleeding, AMS, confusion->start plasmapheresis to tx
diagnosis - MGUS -2
m-protein <10%
no related orgain impairment
diagnosis - asymptomatic myeloma -3
m-protein >30g/L
bone marrow plasma cells >10%
no related orgain impairment
diagnosis - symptomatic myeloma -2
m-protein 10%
orgain impairment = CRAB
staging - ISS -3
stage I: B2M 3.5 =OS 62 mo
stage II: neither I or III =OS 44 mo
stage II: B2M >5.5 =OS 29 mo
staging - mSMART - high risk -3
FISH del 17p, t14;16, t14;20
staging - mSMART - intermediate risk -3
FISH t4;14, cytogenetic del 13q OR hypoploidy
staging - mSMART - standard risk -3
hyperploidy, FISH t11;14 OR t6;14
response criteria - CR -3
- serum and urine immunofixation (-)
- no soft tissu plasmacytomas
- <5% plasma cells in BMBx
- *this will not be on test
how do you decide if autoSCT eligible? -3
age, PS, co-morbidity
if potential autoSCT candidate should you use melphalan? -1
Don’t use alkylator (melphalan) based chemo in induction. melphalan at high doses is toxic to stem cells
induction tx - non-HSCT - preferred regimens -5
bortezomib-dex lenalidomide-low dose dex melphalan-pred-bortezomid melphalan-pred-thalidomide melphalan-pred-lenalidomide
induction tx - non-HSCT -MP vs MPT
OS 64 vs 84% @3yr
CR 7 vs 28%
PFS 27 vs 54% @2yr
induction tx - non-HSCT -MP vs b-MP
OS not reported
CR 4 vs 30%
induction tx - non-HSCT -are 4 drugs better than 3 drugs? VMP vs VMPT
NO.
OS 89 vs 87% @3yr
CR 24 vs 38%
induction tx - HSCT candidates- concepts of dex, L, and T combo’s -
- low dose dex-L >high dose dex-L: CR+VGPR 50 vs 40%
- dex-T > dex alone: CR+VGPR 44 vs 16%
- VAD (vinc-doxo-dex) used previously->CR 28%, replaced by DvD (peg doxo-vinc-dex)
lenalidomide and autoSCT -2
lenalidomide->cummalitive tox to bone marrow, collect cells prior to 4-6 cycles of tx
induction tx - HSCT candidates- preferred regimens -9
bortezomib-dex bortezomib-dex-cyclophos bortezomib-doxo-dex bortezomib-lenalid-dex bortezomib-thalid-dex lenalid-dex OPTIONAL DvD (liposomal doxo-vinc-dex) thalid-dex dex
What is the effect of induction regmen on OS post HSCT?
higher CR in induction = higher CR post HSCT; choose induction regimen that obtains highest CR in induction as has implications post tx
DVT risk - T, L, dex -
T, dex D1-4,9-12,17-20: 17%
L, dex D1-4,9-12,17-20: 26%
L, weekly dex: 12%
thromboembolism px -T, L, dex -3
- first 6 mo: ASA 6.4%, warf 8.2%, lmwh 5%
- entire f/u: ASA 8.6%, warf 10%, lmwh 7.8%
- NO CLEAR BEST CHOICE
nuances of HCT -4
-2x10^6 CD34+/kg (watch melphalan, lenalidomide)
-inc harvest with cyclophos+gcsf
chemo-mobilization with cyclophos MAY overcome lenalid TOX (use if >4cycles L)
-if >65y->red cyclophos OR plerixafor
HCT priniciples ???
benefit to 2nd autoSCT if less than VGPR to 1st
lack of convincing data to support using autoSCT -> reduced intensity chemo vs tandem autoSCT
do NOT use alloSCT as 1st line
Risks for POOR mobilization -6
age, melphalan, thalidomide >4cycles, extensive prior tx, prolonged dz duration, extensive XRT to BM
maintaining remission post HSCT remains a primary objective - T, L maintenance
both T and L have a role in improving OS post HSCT
second primary malignancies -lenalidomide maintenance
4-7% vs 1-2.6% with placebo
salvage regimens - if remission greater than 6 months, repeat original, otherwise -13
bendamustine, bortezomib (B), BD, B-lena-D, B-lipo dox, CyBorD, Cy-lenaD, D-cy-etop-cis, D-thal-cis-doxo-cy-etop (DT-PACE) +/- B =VDT-PACE, high dose Cy, lena-D, thal-D
skeletal related events -5
hypercalcemia of malig, path fx, bone pain, spinal cord compression
Tx: xrt to bone, bone surgery
bisphosphonates in MM (ASCO)
- lytic bone dz: pam 90 q3-4 wks, ZA 4 q3-4wks FOR 2 YEARS, then resume with onset of new SRE
- indolent: not suggested
- osteopenia WITHOUT lytic dz: may consider
- pain control: adjunctive, multimodal tx
bisphosphonate monitoring -5
???
albuminuria, azotemia, SCr (prior to each dose, hold tx for deteriation in renal func until return to within 10% of baseline). FOLLOW INFUSION TIME GUIDELINES look up
osteonecrosis of the jaw associations -3
duration of exposure, dental procedure, concurrent thalidomide
renal impairment -2
#bor-D to rapidly reverse disease-induced nephropathy #lenalid dose adjusted for GFR #melphalan 140mg/m2 for CrCl <60
