Multiple myeloma is a hematologic cancer caused by the clonal expansion of malignant plasma cells, leading to various complications such as anemia, bone disease, and renal dysfunction. The etiology is not completely understood, though factors include genetic alterations and environmental exposures. Diagnosis involves a comprehensive workup, and treatment options range from autologous stem cell transplantation to various chemotherapy regimens based on patient eligibility.

1. MULTIPLE MYELOMA
PRESENTED BY:DR VARA PRASAD
MODERATOR:DR PANKAJ BANSAL
PROFESSOR

2. Multiple Myeloma
• Introduction
• Epidemiology
• Etiology
• Pathophysiology
• Clinical features
• Diagnostic Work Up
• Classification and staging
• Prognostic Factors
• Treatment
• Follow Up

3. DEFINITION
Myeloma is a disease characterized by clonal expansion of
malignant plasma cells that accumulate in the marrow, leading to
anemia and associated cytopenias,
hypogammaglobulinemia, osteolytic bone
disease,hypercalcemia, and renal dysfunction

4. SPECTRUM OF MYELOMA

5. •EPIDEMIOLOGY
•INCIDENCE AND PREVALENCE
• Myeloma represents the second most common hematologic
cancer,accounting for 1.4 percent of all cancers and 10 percent
of hematologic malignancies

6. ETIOLOGY
• The etiology and the mechanisms of myeloma progression are still largely
unknown.Several epidemiologic reports have demonstrated an increased risk of
myeloma or MG (up to fourfold) in first-degree relatives of individuals affected by
plasma cell dyscrasias
• Occupational exposure to pesticides,organic solvents (benzene, petroleum
derivatives, styrene) or chronic radiation have been alleged to be associated with
myeloma in some studies
• Exposure to acute radiation, as in atomic bomb survivors increases the overall
rate of MG or myeloma after 15 to 20 years and accelerates MG transformation
to myeloma.
• People exposed to fresh wood, wood dust, or working in saw mill factories had
an increased risk of myeloma in some studies

7. Genetic causes: Chromosomal alterations identified

10. CLINICAL AND LABORATORY FEATURES

11. RENAL DISEASE
• Renal insufficiency is related to two major causes:
• myeloma cast nephropathy (also called light-chain cast nephropathy or
myeloma kidney) and hypercalcemia
• In myeloma cast nephropathy, the tubular absorptive capacity for light
chains is overwhelmed, leading to the formation in the distal convoluted
tubule (DCT) of the nephron of tubular casts. These tubular casts derive
from the binding of precipitated light chains to Tamm-Horsfall mucoprotein
(uromodulin) and can obstruct the DCT and parts of the ascending loop of
Henle, initiating a giant cell reaction which leads to interstitial inflammation
and fibrosis (interstitial nephritis)

12. • PAIN
• Back or chest bone pain as result of vertebral or rib fractures at sites of
osteopenia or from lytic bone lesions is present at the time of diagnosis in
approximately 60 percent of patients.247 The pain is usually worse with
movement and at night. Pathologic fractures of long bones can ensue as well.
• INFECTIONS
• Myeloma patients are at an increased risk for infections that represent a
leading cause of morbidity and mortality.
• Several aspects contribute to infection risk, including immune dysfunction in
the innate and adaptive immune systems,335 extrinsic factors, like type and
duration of therapy (e.g., cytotoxic agents, glucocorticoids, lenalidomide,
autologous/allogeneic hematopoietic stem cell transplantation), and physical
factors, such as age, coexisting comorbidities, hypoventilation secondary to
pathologic fractures, indwelling vascular catheters and impaired mucosal
integrity.
• A broad immune dysfunction involving B lymphocytes,T lymphocytes, NK cells,

13. • NEUROPATHY
• Local myeloma growth can cause polyneuropathy by spinal cord or peripheral nerve compression, even
though polyneuropathy is not a common presenting symptom, unless in the context of perineuronal or
perivascular (vasa nervorum) amyloid deposition.
• POEMS syndrome, or osteosclerotic myeloma, is an exception, where complete polyneuropathy is
practically always present along with organomegaly, endocrinopathy, monoclonal gammopathy, and skin
changes.
• The pathogenesis of POEMS syndrome is largely unknown, but chronic overproduction of
proinflammatory cytokines, such as VEGF, plays a major role.
• HYPERVISCOSITY
• monoclonal IgMs display a higher intrinsic viscosity than other immunoglobulins.
• Cutaneous or mucosal bleeding is very common in hyperviscosity syndrome, together with blurred vision,
headache, vertigo,dizziness, nystagmus, deafness, and ataxia.
• Circulatory problems affecting cerebral, pulmonary and renal circulation can rarely ensue in the presence
of high blood viscosity

15. Free light-chain assay description. Normal immunoglobulins are composed of two heavy chains and
two
light chains, which together form a constant region and a variable region, capable of recognizing
specific antigens. The free lightchain assay is used to quantify the amount of free light chains in
myeloma patients and to specifically recognize a “hidden” antigenic region (in red) that is normally not
detectable from intact
immunoglobulins.

16. DIAGNOSTIC WORKUP

26. STAGING

27. TREATMENT
• TREATMENT IS DIVIDED BASED ON STEMCELL TRANSPLANT ELEGIBLE
CRITERIA
• DETERMINING TRANSPLANT ELIGIBILITY
• Autologous hematopoietic cell transplantation (HCT) results in superior event-free and overall
survival rates when compared with combination chemotherapy
• All patients should be evaluated at diagnosis for transplant eligibility so that the risks and benefits
of autologous HCT can be reviewed with those eligible
• A minority of patients will be eligible for allogeneic HCT, but the value of allogeneic approaches in
myeloma remain investigational

28. • NOT Eligible for Autologous HCT
• • Age >77 years
• • Direct bilirubin>2.0 mg/dL (34.2 μmol/liter)
• • Serum creatinine>2.5 mg/dL (221 μmol/liter)
• • ECOG performance status 3 or 4 unless due to bone pain
• • New York Heart Association functional status Class III or IV

29. • Autologous transplantation
• Patients < 65-70 years
• Treatment related mortality 10-20%
• Response rate 80%
• Long term survival 40-50%
• Conventional allogeneic transplantation
• Patients < 45-50 years with HLA-Identical donor
• Treatment related mortality 40-50%
• Long term survival 20-30%

31. ACCORDING TO NCCN GUIDELINES

35. • Treatment recommendations for maintenance therapy
• Lenalidomide 10 mg/day on days 1-21 every 28d or
• Thalidomide 50 mg/day to start, escalated to 200 mg/day, titrated to tolerance

37. • Salvage therapy regimens
• Panobinostat 20 mg PO once every other day for three doses/week (on days1, 3, 5, 8, 10, and 12)
of weeks 1 and 2 of each 21-day cycle for eight cycles plus bortezomib and dexamethasone;
consider continuing treatment for an additional eight cycles for patients with clinical benefit.
• Lenalidomide 25 mg/day PO on days 1-21 plus dexamethasone 40 mg/day PO on days 1-4, 9-12,
and 17-20 of each 28-d cycle for the first four cycles of therapy and then 40 mg/day PO on days 1-4
thereafter, every 28 d, who have received at least one prior treatment
• Pomalidomide is a thalidomide analogue indicated for patients who have received at least two prior
therapies (including lenalidomide and bortezomib) and have disease progression on or within 60
days of completion of the last therapy ; Dosage is 4 mg PO QD on days 1-21 of repeated 28-day
cycles until disease progression; may be given in combination with dexamethasone

38. • Carfilzomib : A proteasome inhibitor, is indicated as monotherapy, in combination with
dexamethasone, or in combination with lenalidomide plus dexamethasone for relapsed or refractory
multiple myeloma in patients who have received at least 1 prior line of therapy Lenalidomide or
thalidomide can be used as single agents in salvage therapy
Daratumumab is an anti-CD38 monoclonal antibody for patients who have received at least three
prior treatments, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or
whose disease is refractory to both a PI and an IMiD; dosage is 16 mg/kg IV infusion once weekly
(weeks 1 to 8); reduce frequency to q2 wk (weeks 9-24) and ultimately q4 wk (week 24 and thereafter)
until disease progression

42. SPOTTERS