multiple myeloma management #multiple myeloma treatment

1. MANAGEMENT OF PLASMA
CELL DISORDERS
Presented by-Dr Alauddin Ansari
Moderator-Dr Faraz Badar
Consultant in charge-Dr Mohsin Khan

2. CONTENT
MGUS
Solitary plasmacytoma
Smoldering myeloma
Multiple myeloma
Primary renal amyloidosis
POEM syndrome

3. MONOCLONAL GAMMOPATHY OF
UNDETERMINED SIGNIFICANCE(MGUS)
• MGUS is an asymptomatic condition
• risk of progression of MGUS to multiple myeloma or related malignancy is
1% per year
• The true lifetime probability of progression is approximately 11% at 25
years.
• RISK FACTORS FOR PROGRESSION
 size of the serum M protein
 the type of immunoglobulin
 the serum FLC ratio

6. SMOLDERING (ASYMPTOMATIC) MYELOMA
• Smoldering myeloma is a precursor to MM
• All patients with smoldering myeloma have a risk of progression to MM.
• the rate of progression varies from months to several years based on
certain risk features.
• RISK STRATIFICATION--The Mayo 2018 20/2/20 criteria
i. percentage of bone marrow plasma cells (BMPC) greater than 20%
ii. M-protein greater than 2 g/dL
iii. FLCr greater than 20

7. • HIGH RISK
≥ 2 factors present),
the estimated median TTP was 29 months
• INTERMEDIATE RISK
1 factor present
 the estimated median TTP was 68 months
• LOW RISK
none of the risk factors present
the estimated median TTP was110 months

8. • LOW/INTERMEDIATE RISK GROUP—
• clinical trial
• observe at 3- to 6-month intervals (category 1)
• HIGH-RISK GROUP-
 clinical trial
 treatment with single-agent lenalidomide only in carefully selected patients
 observation at 3 moth interval
NCCN GUIDELINES-2023

10. SOLITARY PLASMACYTOMA
• Radiation therapy has been shown to provide excellent local control
of solitary plasmacytomas.
• surgery may be performed if a lesion causes structural instability of
bone or rapidly progressive neurologic compromise
• after gross tumor excision, RT is still indicated because of a high
likelihood of microscopic residual disease.

11. • The radiation dose used in most published papers ranges from 30 to 60 Gy
• The NCCN Panel recommends primary radiation therapy (40–50 Gy in
1.8–2.0 Gy/fraction) to the involved field

12. Multiple Myeloma
DEVITA

14. Treatment options
Old regimen
Dexamethasone
Vincristine
Adriamycin
Dexamethasone
VAD regimen
Novel agents
Bortezomib
Lenalidomide
Dexamethasone
Carflizomib
Daratumumab

15. Bortezomib(velcade)
Intravenous/subcutaneous

17. Vd vs VAD

20. (ENDURANCE E1A11)
• bortezomib/lenalidomide/dexamethasone vs
carfilzomib/lenalidomide/dexamethasone as induction therapy

21. Response To Induction

24. • After a median follow-up of 9 months, median PFS was 34.4 months with
the bortezomib-regimen versus 34.6 months with the carfilzomib regimen
• Based on this data, VRd should remain the standard of care for
initial therapy of multiple myeloma

28. • despite a higher rate of complete or partial response with high-dose
therapy, overall 1-year survival was 87% in the high-dose group versus
96% in the low-dose group (P = .0002), largely because of the
significant toxicity of the former.
• As a result, the trial was stopped and patients on high-dose therapy
were crossed over to low-dose therapy

29. THALIDOMIDE
• Thalidomide was the first new drug in myeloma in over four decades
• thalidomide and dexamethasone (TD) yields a response rate of 64% (similar
to VAD), without compromising the ability to collect stem cells, but with a
rate of deep vein thrombosis of 12%
• The use of thalidomide in pregnancy is absolutely contraindicated
• The main side effects of thalidomide are neuropathy, sedation, fatigue,
rash, constipation, and deep vein thrombosis (DVT)
• All patients receiving thalidomide need DVT prophylaxis with aspirin or
low-molecular-weight heparin. Dosage--100 to 200 mg orally daily

30. GENERAL CONSIDERATIONS FOR MYELOMA
THERAPY
• The general approach to myeloma is to provide sequential therapies
to patients, knowing each will not be curative but will prolong the
period of disease control. The goal is to convert the disease into a
chronic illness---(perez)
• Patients should receive a triplet regimen (2 drug classes and steroids)
if they can tolerate it.(perez)

31. • Patients with poor performance status or who are frail can be started
on a 2-drug regimen, with a third drug added once performance
status improves.
• In transplant eligible patient Exposure to myelotoxic agents should be
limited

32. • Administer herpes zoster prophylaxis for all patients treated with
proteasome inhibitors (PIs), daratumumab, isatuximab-irfc, or
elotuzumab.
• Pneumocystis jiroveci pneumonia (PJP) should be given if receiving steroids
• Subcutaneous bortezomib is the preferred method of administration
• Both weekly and twice-weekly dosing schemas of bortezomib may be
appropriate; weekly preferred(dose 1.3 mg/m2)
• Carfilzomib may be used once or twice weekly and at different doses

33. Transplant eligible patient
• In patients who are candidates for ASCT, various regimens can be
used to induce response prior to stem cell collection
• The NCCN Panel prefers 3-drug regimens as the standard for primary
treatment of all patients who are transplant eligible
• This is based on improved response rates, depth of response, and
rates of progression-free survival (PFS) or OS seen with 3-drug
regimens in clinical trials

34. Preffered
Other recommended
Useful
Study about that

36. TRANSPLANT NON ELIGIBLE PATIENT
• the 2- drug regimens are still listed as options with a note that a
triplet regimen is the standard therapy but patients who cannot
tolerate a 3-drug regimen due to poor performance status, can be
started with a 2- drug regimen, and the third drug can be added if the
performance status improves

39. ROLE OFRADIOTHERAPY IN MM
• TOTAL BODY IRRADIATION
• HEMIBODY RADIATION
• LOCAL EXTERNAL BEAM FOR PALLIATION

40. TBI
• Some high-dose chemotherapy protocols for multiple myeloma incorporate
total body irradiation (TBI) into the conditioning regimen
• IFM [Intergroupe Francophone du Mye’lome] trial 9502-
 Melphlan 200mg/m2 alone vs melphalan 200mg/m2 + TBI 8gy/4#
 TBI-containing arm suffered more grade 3 or 4 mucosal toxicity, heavier transfusion requirement, and
longer hospitalization stay
 The event-free survival was no different between the two treatments
 TBI is now rarely used in conditioning regimens for ASCT, unless it is part of a research clinical trial

41. HEMIBODY RADIATION
• Diffuse bone pain involving wide areas of the skeleton can be
effectively palliated by half-body radiation with single doses of 5 to 8
Gy, although this is rarely used now
• A phase III trial by the South West Oncology Group
Survival in this trial was significantly poorer with radiation compared
with chemotherapy
At present, there is no standard role for sequential hemibody
radiation as systemic treatment for myeloma outside of a clinical trial

42. LOCAL EXTERNAL BEAM FOR PALLIATION
• The most common use of RT is the palliative treatment of bony disease
and relief of compression of the spinal cord,cranial nerves, or peripheral
nerves.
• 40% of patients with multiple myeloma will require palliative radiation
therapy for bone pain at some time during the course of their disease
• Doses of 10 to 20 Gy (in 5 to 10 fractions) are effective.
• Leigh et al. found a symptomatic response rate of 97% (complete pain
relief in 26% and partial relief in 71%) after an average dose of 25 Gy

43. • A multicenter study (not restricted to
myeloma patients) suggested that a
longer fractionated regimen (30 Gy in
10 fractions or higher) was associated
with better neurologic recovery than 20
Gy in 5 fractions or a single 8 Gy.
• another recent prospective randomized
trial showed that 20 Gy in 5 fractions
was equivalent to 30 Gy in 10 fractions
in terms of 6-month functional
outcome and local control

44. Hematopoietic Cell Transplantation
• AUTOLOGOUS STEM CELL TRANSPLANTATION
ASCT has become the standard of care for eligible patients,
it has been demonstrated in multiple trials to improve the likelihood
of complete response, prolong disease-free survival, and extend
overall survival

45. • TANDEM TRANSPLANTATION
Tandem or double transplantation refers to a planned second ASCT after
the patient has recovered from the first within 6 months of the first course
A phase III trial in France evaluated tandem transplant versus single ASCT
and demonstrated superior overall survival in the tandem group
consider tandem transplantation only in patients whose response to the
first ASCT is suboptimal

46. • ALLOGENEIC STEM CELL TRANSPLANTATION
Myeloablative stem cell transplant is perhaps the only current
potential cure for patients with myeloma, as the graft is not
contaminated with tumor cells.
However, its use is very limited because of the lack of donors, age
restriction, high treatment-related mortality, and graft versus host
disease.

47. RESPONSE EVALUATION
• Patients on treatment should be monitored for response to therapy
and for symptoms related to disease and/or treatment
• According to the NCCN Panel, response should be assessed using the
IMWG criteria
• The same imaging modality used during the initial workup should
ideally be used for the follow-up assessments

48. • patients are consider for therapy until the best response is reached
• The optimal duration of primary therapy after achieving maximal
response is unknown
• maintenance therapy or observation can be considered beyond
maximal response.

51. SYSTEMIC AL (IMMUNOGLOBULIN LIGHT
CHAIN) AMYLOIDOSIS
• Amyloid is a fibrillar proteinaceous material that can be deposited in
various tissues
• AL amyloidosis refers to the type of amyloidosis derived from the
variable portion of a monoclonal light chain in rare instances, intact
monoclonal light chain, and occurs as a result of a clonal plasma cell
proliferative disorder.
• AL amyloidosis may be localized (a benign disorder) or systemic

54. SUPPOTIVE CARE
BONE DISEASE
All patients receiving primary myeloma therapy should be given bone-
targeting treatment bisphosphonates (category 1) or denosumab
A baseline dental exam is strongly recommended
Continue bone-targeting treatment (bisphosphonates or denosumab) for
up to 2 years
The frequency of dosing (monthly vs. every 3 months) would depend on
the individual patient criteria and response to therapy.
NCCN Guidelines Version 2.2023 Multiple Myeloma

55. HYPERCALCEMIA
• Hydration, bisphosphonates (zoledronic acid preferred),
denosumab, steroids, and/or calcitonin are recommended
HYPERVISCOSITY
 Plasmapheresis should be used as adjunctive therapy for
symptomatic hyperviscosity

56. ANEMIA
Consider erythropoietin for anemic patients
INFECTION
Intravenous immunoglobulin therapy should be considered in the
setting of recurrent serious infection and/or hypogammaglobulinemia
(IgG ≤400 mg/dL)
The pneumococcal conjugate vaccine should be given followed by the
pneumococcal polysaccharide vaccine one year later

57. • Consider 12 weeks of levofloxacin 500 mg daily at the time of initial
diagnosis for MM.
• Reactivation of hepatitis B virus (HBV) is a complication in patients
receiving carfilzomib or daratumumab. Therefore, testing for hepatitis
B in these patients is recommended
• Pneumocystis jiroveci pneumonia (PJP), herpes zoster, and antifungal
prophylaxis is recommended if high-dose dexamethasone is used
• Prophylactic antiviral therapy is recommended for all patients
receiving PI based therapies

58. • VENOUS THROMBOEMBOLISM (VTE)
• Aspirin 81–325 mg once daily
• Rivaroxaban 10 mg daily
• LMWH

59. POEMS SYNDROME
• The major clinical features are a predominantly
motor chronic inflammatory demyelinating polyneuropathy,
sclerotic bone lesions
 hepatomegaly
hyperpigmentation
hypertrichosis
gynecomastia
testicular atrophy
clubbing
polycythemia
thrombocytosis

60. • If the lesions are in a limited area, radiation therapy (40 to 50 Gy)
produces substantial improvement of clinical symptoms and signs in
more than 50% of patients.
• treatment is similar to multiple myeloma

61. questions
• A patient diagnosed with MGUS low risk.the absolute risk of 20 year
progression
A. 2%
B. 5%
C. 10%
D. 15%

62. • Dose of RT in solitary plasmacytoma
A. 45-55gy
B. 40-50gy
C. 45-50gy
D. 35gy

63. • most appropriate Treatment of transplant eligible MM patient
A. Borte+lenid+dexa
B. Borte+dexa
C. Linid+dexa
D. All of above

64. • Regimen used for primary amyloidosis
A. Borte+lenid+dexa
B. borte+cyclophosphamide+dexa
C. Daratumumab +lenid+dexa
D. Borte+dexa


65. • A 60 yr male patient reffered to RT opd from medicine side with
following investidations
• Serum monoclonal protein-3.5g/dl
• Clonal BM plasma cell-26%
• Serum calcium-9.5
• Hb-12.8
• S creatinine-1.9
Q.How do u procede ?

66. • PET SCAN –no bony lesion
• Next...
• FLC ratio-10
• NEXT….
• WHOLE BODY MRI—
• ?WITH/WITHOUT CONTRAST
• MRI-NEGATIVE
WHAT IS DIAGNOSIS
TREATMENT?