Myeloma Drugs

Daratumumab – CD38 – check type and screen first – m spike on the spep separate location,
serum sickness, shingles
Lenalidamide – VTE, increased 2/2 malignancy rash
Pomolidamide rash and VTE
Thalidomide
Melphalan
Elotuzumab – slam7 – myeloma and NK cells
Dexamethasone
Bortezomib – neuropathy, zoster ,
Ixazomib – anti CD38
Isatuximab – anti CD38
Panobinostat
Selinexor – XPO 1 inhibitor
Cyclophosphamide
Plerixafor – GCSF mobilizer for auto transplant cell collection
Carfilzomib - CHF
Venetoclax – BCL2 inhibitor – better for t(11,14) – but not the standard of first line care
Belantatumab anti CD269 – ophthalmology corneal disease 4th line
Idecabtagene vicleucel BCMA b cell maturation antigen for cart T chimeric antigen receptor
antigen for t cells- for multiple myeloma
Melphalan flufenamide – aminopeptidase alkylating agent – higher levels of melphalan 4 th line –
decrease chance of Stem Cells harvesting in future

Amyloidosis
ATTR – patisiran for neuropathy
ATTR – treat with liver transplant
- tafamidis if not candidate – binds to TTR and stabilizes it preventing further aggregations
/ damage
If isolated, can give surgery
Doxycycline may help

Waldenstroms
- bing neel syndrome – CNS infiltration - brutinib

Low-risk MGUS
These patients have a serum M spike < 1.5 g/dL, IgG isotype, and a normal Free
light chain ratio
For this cohort group, the absolute risk of progression at 20 years is 5%, compared
to 58% for the high-risk group. Patients with low-risk MGUS do not require a bone
marrow examination or skeletal radiography if the clinical evaluation, CBC, and
serum creatinine and calcium values suggest only MGUS.
Intermediate- and high-risk MGUS
Patients with intermediate-risk MGUS have one or two abnormal risk factors, while
all three risk factors are abnormal in those with high-risk MGUS. These risk factors
include a serum M protein is > 1.5 g/dL, the protein type is IgA or IgM, and the FLC
ratio is abnormal.
Intermediate-risk and high-risk patients should have a bone marrow aspirate and
biopsy with both conventional cytogenetics and FISH.
Intermediate- or high-risk MGUS patients with the IgM isotype should have a CT
scan of the abdomen since asymptomatic retroperitoneal lymph nodes may be
present. Despite the high-risk nature of this MGUS, treatment is not indicated
unless it is part of a clinical trial.

Solitary plasmacytoma of bone (SPB):

--Biopsy-proven solitary tumor of bone with evidence of clonal plasma cells
--Cross sectional imaging must show no other lytic lesions
A Magnetic resonance imaging (MRI) is normal except for the primary solitary lesion.
--Bone marrow aspirate and biopsy must contain no clonal plasma cells
--There is no anemia, hypercalcemia, or renal insufficiency that could be attributed to a
clonal plasma cell proliferative disorder
--The presence of a monoclonal (M) protein does not exclude the diagnosis of SPB, and
a small M protein may be present in 30 to 75 percent of cases. This M protein may or
may not disappear with treatment

Smoldering (Asymptomatic Myeloma):

Serum monoclonal protein ≥ 3 g/dL
Or
Bence-Jones protein ≥ 500 mg/24 hours
And/or
Clonal bone marrow plasma cells 10-59%
And
Absence of myeloma-defining events or amyloidosis. If the skeletal survey is negative,
one should assess for bone disease with whole body MRI or PET-CT
Active (Symptomatic Myeloma):
Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary
plasmacytoma
And
Any one or more of the following myeloma-defining events:
--Calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75
mmol/L (>11 mg/dL)
--Renal insufficiency (creatinine >2 mg/dL) or CrCl <40 mL/min
--Anemia (Hb <10 g/dL or Hb >2 g/dL below the lower limit of normal)
--One or more osteolytic bone lesions on skeletal radiography, CT, or FDG PET/CT
--Clonal bone marrow plasma cells ≥60%
--Abnormal serum Free light chain ratio ≥100 (involved kappa) or ≤0.01 (involved
lambda)
-- >1 focal lesions on MRI studies ≥ 5 mm

International Staging system:

Stage I: B2 microglobulin < 3.5 mg/dL and Albumin > 3.5 g/dL
Stage II: Albumin < 3.5 g/dL
Stage III: B2 microglobulin ≥≥ 5.5 mg/dL
There is also a Revised International Staging system that is oftentimes used to
prognosticate patients with Myeloma.
Revised-International Staging system (ISS):
Stage I: ISS stage I and standard-risk chromosomal abnormalities by FISH and
serum LDH ≤ the upper limit of normal
Stage II: Not R-ISS stage I or III
Stage III: ISS stage III and either high-risk chromosomal abnormalities by FISH
or Serum LDH > the upper limit of normal
Standard-risk: No high-risk chromosomal abnormality
High-risk: Presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16)

Mutations:

t(11;14) translocation juxtaposes the cyclin D1 gene with the IgH promoter, is
associated with a neutral to favorable prognosis in multiple myeloma.

Multiple myeloma (MM) cells, particularly in those harboring t(11;14), express high
levels of BCL-2 relative to BCL-XL and MCL-1. – respone to venetoclax

Dr. Weil lecture:

Plasma cell leukemia – need VRD PACE, need auto SCT

Diagnosis: standard cytogentics and FISH 17p13, t(4;14), t(14;16)

MRD – plasma cell flow cytometry

SR007 – RD vs VRD
IFM DFCI 2009 – RVD vs transplant arms – CR and VGFR favor transplant and MRD