MULTIPLE MYELOMA Review & Update for Primary Care. Dr. Joseph Mignone 21st Century Oncology

Size: px

Start display at page:

Download "MULTIPLE MYELOMA Review & Update for Primary Care. Dr. Joseph Mignone 21st Century Oncology"

Ezra Carroll
8 years ago
Views:

1 MULTIPLE MYELOMA Review & Update for Primary Care Dr. Joseph Mignone 21st Century Oncology

2 OVERVIEW Identify the diagnostic criteria for multiple myeloma Compare first & second line therapies, using data from clinical trials Describe adjunctive & supportive therapies

3 MULTIPLE MYELOMA Plasma cell malignancy Second most common hematologic malignancy Characterized by monoclonal immunoglobulin - MGUS - Smoldering MM - Plasmacytoma

4 EPIDEMIOLOGY 19,900 new cases per year, 50,000 total cases, 2% cancer deaths in the U.S. Higher incidence in African Americans, Pacific Islanders. Median age 71 years Exposure to radiation, petroleum, pesticides & Agent Orange

5 PRESENTING FEATURES Bone disease & hypercalcemia Recurrent infections Anemia and fatigue Renal failure due to multiple causes Neuropathy Asymptomatic in minority of the patients

7 INITIAL DIAGNOSTIC EVALUATION History and physical examination Blood work-up CBC with diff and platelet counts BUN, Creatinine Calcium, Albumin Serum protein electrophoresis (SPEP) and immunofixation Quantitative immunoglobulins Serum free lyte chains B2- microglobulin Serum viscosity if CNS signs

Serum protein electrophoresis (SPEP) and immunofixation Quantitative

8 INITIAL DIAGNOSTIC EVALUATION Urine Bence Jones quantitation (lambda light chains) 24hr protein electrophoresis (UPEP) and immunofixation Other Skeletal survey Unilateral bone marrow aspirate and biopsy for histology, cytogenetics and FISH

electrophoresis (UPEP) and immunofixation Other Skeletal

10 BONE IMAGING IN MM Skeletal Survey is the primary diagnostic test to detect destructive bony lesions in multiple myeloma MRI is useful in assessing whether spinal compression fractures are due to a focal mass or from osteopenia due to increased osteolysis PET scans can be used to detect soft tissue or bone metastases

$spinal compression fractures are due to a focal mass or from osteopenia due to$

11 LYTIC LESIONS IN MM

12 PLASMA CELL DYSCRASIA MGUS Premalignant condition Abnormal production of monoclonal Ig by plasma cell This also happens in MM, however: Fewer M-proteins No End Organ Damage 2 % population >50 years Risk of progressing to MM > 1% each year

happens in MM, however: Fewer M-proteins No End Organ

13 PLASMA CELL DYSCRASIA 80% of cases of MM arise De Novo 20% percent from MGUS Risk factors for progression from MGUS to MM include: An elevated M protein level >1.5 g per dl A non-igg MGUS Abnormal free light chain ratio Patients with MGUS should be monitored closely q6 to 12 months

14 PLASMA CELL DYSCRASIAS Solitary plasmacytoma of bone Solitary bone lesion due to plasma tumor cells Normal skeletal survey and MRI skull, spine and pelvis Normal BM plasma cells Multiple Myeloma Marrow plasmacytosis >10% Monoclonial immunoglobin >3.0g/dl Suppressed uninvoled immunolobins Lytic bone lesions and/or diffuse osteopenia Related organ or tissue impairment

Multiple Myeloma Marrow plasmacytosis >10% Monoclonial immunoglobin >3.

15 PLASMA CELL DYSCRASIAS Soldering Myeloma Monoclonial immunoglobin >3.0 g/dl and/or BM plasma cells >10% No lytic lesions, no anemia, hypercalcemia or renal disease

16 MONOCLONAL PROTEINS IgG 60% IgA 20% IgD 2% IgE <0.1 % Light Chain only 18% Nonsecretory <5%

17 DURIE-SALMON STAGING SYSTEM Stage I (All) Hgb > 10 g/dl Normal calcium Normal bones or Solitary plasmacytoma Low M-protein IgG < 5 g/dl IgA < 3 g/dl Light chains < 4 g/24 h Stage II not fitting I or III Stage III (Any) Hgb < 10 g/dl Hypercalcemia Multiple lytic lesions High M-protein IgG > 7 g/dl IgA > 5 g/dl Light chains > 12 g/24 h

g/24 h Stage II not fitting I or III Stage III (Any) Hgb < 10 g/dl Hypercalcemia

18 INTERNATIONAL STAGING SYSTEM for SYMPTOMATIC STAGE CRITERIA I B2m< 3.5 mg/l albumin > 3.5 g/dl MYELOMA MEDIAN SURVIVAL 62 (MO) II Not Stage I or III 44 III B2m > 5.5 mg/l 29

19 TREATMENT SOLITARY PLASMACYTOMA Radiation therapy 45 to Gy Follow up CBC, SPEP, UPEP, chemistry every 3 months Bone Survey +/- CT scan or MRI every 6 mo Yearly evaluation after one year and no disease

21 NEWLY DIAGNOSED PATIENTS In most centers in the U.S., patients are excluded for any of the following Age > 77 Direct bilirubin >2.0 mg/dl ECOG performance status 3 or 4 NYHA functional Class 3-4

22 THERAPY OPTIONS: NON-TRANSPLANT CANDIDATE Melphalan + Prednisone (MP) Melphalan + Prednisone + Thalidomide (MPT) Dexamethasone (DEX) Thalidomide + Dexamethasone (Thal/Dex) Lenolidomide + Dexamethasone (Rev/Dex) Bortezomib +/- Dexamethasone (Vel/Dex)

24 MELPHALAN + PREDNISONE Response rate = ~ 40% Duration of response: 18 months Overall survival: months Cycle is repeated every 4-6 weeks

25 TREATMENT OPTIONS RELAPSED PATIENT Since no therapy is curative, all options need to be tried sequentially No good data on optimum sequence or regimen All patients should be encouraged to participate in ongoing clinical trials Cumulative toxicities from prior therapies may influence decision

26 SALVAGE Therapy Thaldomide + Dexamethasone (Thal/Dex) Lenolidomide + Dexamethasone (Rev/Dex) Bortezomib +/- Dexamethasone (Vel/Dex) Pegylated + Liposomal Doxorubicin (PLD) based regimens

27 VTE PREVENTION with IMMUNOMODULATING AGENTS As single agents: minimal risks; prophylaxis may be considered Concomitant chemotherapy: especially Dex, anthrycylines &ESAs, increase risk as much as 58% Low dose warfarin: not protective ASA: adequate in lower brisk patients receiving dex and an immunomodulator LMWH (enoxaparin 40mg QD), full dose warfarin, are recommended for patients at high risk for VTE

28 TREATMENT OF BONE DISEASE Bisphosphonates Radiotherapy Treatment of myeloma Surgical procedures Vertebroplasty Balloon Kyphoplasty

30 ISSUES WITH BP THERAPY Renal Toxicity Osteonecrosis of the jaw Decreases skeletal events by 50%; patients still progress but at a slower rate No clear anti-tumor activity

32 ANEMIA TREATMENT GOALS Treat the underlying malignancy Decrease fatigue Decrease need for PRBC Treat the patient, not the number

33 ASCO PRACTICE GUIDELINES for ESA (2007) General Review peripheral smear; consider iron, folate, and B12 deficiency as potential causes for anemia, assess for occult blood loss. Comparative effectiveness: Agents are considered equivalent in terms of safety and efficacy No reason to believe that a patient who fails to respond to one ESA will have a response to a different ESA

35 CARFIZOMIB Second generation selective proteasome inhibitor Approved in patients that failed 2 previous lines of therapy including Velcade and Revlimid Most common toxicities were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexa Over all response was 48% with median duration of 13 months

36 PAMALIDOMIDE Thalidomide analog with activity alone or with Dexamethasone Approved in patients that failed 2 previous lines of therapy including Velcade and Revlimid Overall response rate was 35% with median duration of 14.9 months Most common toxicities were neutropenia, anemia, thrombocytopenia, pneumonia, and bone pain All patients received aspirin prophylaxis

Outline. Question 1. Question 2. What is Multiple Myeloma? Andrew Eisenberger, MD

Outline. Question 1. Question 2. What is Multiple Myeloma? Andrew Eisenberger, MD Outline A Disease Overview June 3, 2013 Andrew Eisenberger, MD Assistant Professor of Medicine Hematology/Oncology Columbia Presbyterian Medical Center Introduction Epidemiology/Risk Factors Clinical Features/Diagnostic