Haematology 3 - Multiple Myeloma Flashcards
What is multiple myeloma?
Disease of plasma cells
Genetic changes during terminal differentiation of B lymphocytes into plasma cells
Expansion of clone malignant immature B cells - myeloma cells
Produce monoclonal protein = detected in blood + urine
Accumulate in bone marrow + blood
What is the molecular biology?
Clonal myeloma cells
Extracellular matrix proteins
Bone marrow stromal cells
Osteoblasts + osteoclasts = bone damage
Tumour necrosis factor
Confer protection against apoptic stimuli
What is the clinical presentation?
CRAB
Calcium increases = confusion, nausea, constipation + kidney stones
Renal impairment = monoclonal light chains block
Anaemia = fatigue, weakness + pallor
Bone lesions = pain, fractures + osteoporosis
Others = frequent infections, peripheral neuropathy + hyperviscosity syndrome
What is the diagnosis?
Blood tests = SPEP + immunofixation (detects M-protein)
Urine tests = light chains
Bone marrow biopsy = clonal plasma cells = main diagnostic
Imaging = x-ray, CT or MRI to assess lytic lesions
Describe International Staging System (ISS)
Stage I = serum B2 microglobulin <3.5mg/L + serum albumin >35g/L
Stage II = neither I or II
Stage III = serum B2 microglobulin >5.5mg/L
Describe the initial therapy considerations
No routine treatment required for asymptomatic disease unless high risk cytogenetics
Symptomatic = treatment of complications prior chemo
Approach to therapy based on whether patient is transplant candidate = performance status, co-morbidities, fragility index
What is the treatment for transplant eligible candidate?
Achievement of complete remission or partial remission prior to transplant
Stem cell harvesting once in remission
Pre-stem cell mobilising regime administered
High dose melphalan + autologous stem cell transplantation = NOT cure but remission = will eventually relapse
Allogenic = 2nd line = higher risk of rejection
Post transplant consolidation
Ongoing treatment = thalidomide maintenance = decrease relapse post-transplant
Describe autologous stem cell transplantion
Stem cell mobilisation = drugs to produce more stem cells
Collection of stem cells = blood or bone marrow
Processing = blood processed through machine to remove stem cells
Conditioning + treatment = high-dose chemo with or without radiotherapy to kill remaining cancer cells + also gets rid of blood-producing cells in the bone marrow
Describe D-VTD chemo regime
Daratumumab = s/c injection
Bortezomib = s/c injection
Thalidomide = oral ON = tired
Dexamethasone = oral = anti-myeloma effect
28 day cycle
Describe Daratumumab
MAb = targets protein on surface of myeloma cells = attach + signals to immune system to destroy
Describe Thalidomide
Immunomodulatory drugs
Teratogenic
Venous thromboembolism
Peripheral neuropathy
Constipation
Haematological toxicity
Describe Lenalidomide
Designed to have reduced incidence of SEs
Higher incidence of myelosuppression
Describe what Proteasome inhibitors
Disruption of proteasome activity results rapid accumulation of incompatible regulatory proteins = induction of apoptotic cascade
Describe Bortezomib
Reversible proteasome inhibition
Directly induces apoptosis
Inhibits NF-Kb pathway
Reduces IL-6 production + signalling
What are the options for transplant non-eligible patients?
Aims = control disease, long progression free survival + overall survival + maintain quality of life
Induction regime = Lenalidomide + Dexamethasone
Thalidomide/Bortezomib + alkylating agent + corticosteroid
What are the supportive therapies?
Bisphosphonate IV = in all patients with chemo = inhibit bone resorption = suppress osteoclast activity
VTE prophylaxis = aspirin, DOAC, warfarin + LMWH
GI protection with steroids
TLS = allopurinol
Infections = anti-viral prophylaxis for all chemo patients
PCP prophylaxis for patients requiring high dose steroids
What are the challenges in treatment?
Autologous stem cell transplantation = prolongs survival BUT not curative
Relapse therapy = NO standard treatment
Needs to be researched extensively
