Multiple Myeloma Group Presentation Overview of Disease Process Introduction Multiple Myeloma (MM) is the uncontrolled proliferation of plasma cells. Causes bone damage, abnormal production of cells in bone marrow, and renal damage (which will be discussed later) Prognosis Currently no approved cure Talk abt how even with remission, ppl typically relapse. Discuss adoptive T cell therapy briefly 5 year survival: 44% Plasma Cells & Antibodies Normally, plasma cells make up 2-3% of cells in the bone marrow . In MM, plasma cells make up >10% of bone marrow cells. 75% of abnormal plasma cells create abnormal antibodies AND parts of a complete antibody called paraproteins, which are light chains also known as Bence Jones proteins. (Antibodies consist of two heavy chains and two light chains). The most common antibodies associated with MM are IgG (60%) and IgA (20%). Multiple Myeloma Progression Stages: Precancerous: Monoclonal Gammopathy of Undetermined Significance (MGUS). “Watchful waiting”, No sx, blood+urine tests. Can turn into other cancers like CLL as well. Criteria: 1. M protein, an immunoglobulin produced by plasma cells <30g/L 2. Plasma cells <10% 3. No CRAB sx Smouldering MM: or Asymptomatic MM. in between MGUS and active MM. M protein >30g/L, plasma cells >10%. Regular blood tests q3-6months No CRAB sx. WILL Eventually develop active MM. If Low risk, ~19yrs after diagnosis Intermediate ~9yrs after, high risk ~2.5 yrs -> no tx unless high risk (will treat like stage 1). Think quality of life, age Active MM: M protein in blood/urine, plasma cells make up >10% of bone marrow, CRAB Other Common Types of MM (CAN form tumors) Plasmacytoma = abnormal plasma cells that form a tumour Solitary Plasmacytoma: abnormal plasma cells collecting in one place to form a solid tumor. No other features of MM, x-ray shows only one lesion. Most common symptom is bone pain at site. Often tx with radiation. ⅓ of people will have solitary plasmacytoma develop into MM -> imperative to treat Extramedullary Plasmacytoma: Start outside of the bone marrow. More rare -> maybe discuss the higher risk of misdiagnosis bc 1. Solid tumor outside bone marrow which is not typical? What are osteoclasts, osteoblasts, and bone marrow stormal cells? (To continue explaining, must give review here): Bone contains osteoblasts, osteoclasts and bone marrow stromal cells. Osteoblasts build bone using Ca2+ and P. Osteoclasts break down bone, by secreting HCl; this causes Ca2+ and P to be released . Bone marrow stromal cells normally regulate hematopoiesis. Osteoclast activity are regulated by osteoblasts, which express ‘RANK L’ ( highlight indicates this is probably TMI that will be simplified later) that bind to ‘RANK’ osteoclasts. This mechanism PROMOTES osteoclast activity Osteoblasts can release ‘OPG’ to stop osteoclast activity. Role of bone marrow stromal cells in promoting MM In MM, there is an adhesion of MM cells to bone marrow stromal cells, helping MM cells to thrive and grow. Some results of this adhesion are: 1. Cytokine mediated cell growth 2. Survival 3. Drug resistance 4. Migration of cells 4 Factors dysregulating osteoblast and osteoclast activity MM cells secrete cytokines that contribute to the spread of MM cells. An example: Interleukin 3 (IL3). IL3 prevents osteoblast progenitor cells, which are precursor cells, from converting to osteoblasts. MM cells secrete DKK1, inhibiting OPG1 production by osteoblasts, leading to increased osteoclast activity MM cells increase osteoclast activity through MIP1 and Rank L. In MM, Interleukin 6 activity (IL6) is increased. IL6 is a cytokine that is a growth factor and a survival factor that inhibits apoptosis. THESE four factors are what ultimately cause INCREASED osteoclast activity and DECREASED osteoblast activity. These are what cause the typical lytic bone lesions. (discuss fractures, osteoporosis later) Problems caused by increased osteoclast activity 1. Increased CA2+ in blood: CATS acronym, nerve issues, dehydration 2. Renal failure due to paraproteinemia: Excessive Immunoglobulins (Ig) and light chains (Bence Jones proteins), will be present in urine (discuss in diagnostic tests) 3. Anemia: 3 mechanisms a. Shift in myeloid progenitor cells (which make RBC) to lymphoid progenitor cells to make more plasma cells. (need to research more on why, maybe to compensate for the body thinking theres insufficient plasma cells?) b. Overcrowding which stops RBC production c. Kidney failure causes decreased erythropoietin production, decreasing erythropoiesis. Symptoms (will add more later) CRAB (hypercalcemia, renal failure, anemia, bone lesions) Bone pain (60%) X-rays abnormality (80%) → lytic lesions, osteoporosis, pathologic fracture, vertebral compression fracture Fatigue (>30%) Weight loss (20%) Anemia (70%) Renal failure (20%) Hypercalcemia (15%) http://www.bccancer.bc.ca/family-oncology-networksite/Documents/FPON%20Myeloma%20Sept%202016%20%28greg%20dueck%29.pdf What we need: Risk Factors, Nursing Role, Staging (i might have staging above, might need to be moved lower? Included below is: Diagnostic Tests,, Treatment, Refer to Catherine’s slides since they're all basically laid out there/ More research needed Diagnosis Serum and urine protein studies Serum electrophoresis & serum protein immunofixation Quantitative immunoglobulins Serum free light chains (bence jones proteins) Urine protein 24 hour Serum calcium, uric acid, and creatinine, CBC Chest radiograph Skeletal survey Urgent MRI or CT of the spine if presenting with back pain and SCC suspected Bone marrow aspiration and biopsy (using FISH probe) Hepatitis testing (idk why?) Standard Treatment Chemotherapy is the treatment of choice Cure is not possible, but chemotherapy offers satisfactory palliation High-dose chemotherapy and autologous hematopoietic stem cell transplant (patients up to 70 years old) Induction therapy consists of bortezomib and dexamethasone Cyclophosphamide added in combination to deepen the remission prior to transplant Bisphosphonates used to prevent skeletal destruction (Pamidronate) Radiation can be used for symptomatic bone lesions or soft tissue plasmacytoma that is unresponsive to primary treatment, pathological fractures, and SCC http://www.bccancer.bc.ca/health-professionals/clinical-resources/cancermanagement-guidelines/lymphoma-chronic-leukemia-myeloma/multiplemyeloma Renal impairment Occurs in up to 25% of patients upon presentation Damage to the renal tubules is caused by free light chains Other causes → dehydration, hypercalcemia, nephrotoxic drugs (ex. NSAIDs), infections Patients presenting with renal failure have a higher early death rate and worse overall prognosis May be the initial manifestation Criteria of Adequate Response to Treatment Improvement of bone marrow function Improvement of kidney function Normalization of serum calcium No new osseous or extra-osseous lesions Resolution of all symptoms Reduction of serum paraprotein < 50% of pretreatment level and urine paraprotein <10% pretreatment level Criteria of Relapse or Progression Progressive risk in paraproteinemia or paraproteinuria by > 25% Development of hypercalcemia Appearance of new osseous or extra-osseous lesions Progressive bone marrow failure Follow up evaluation 1 month → CBC, serum creatinine, calcium, serum protein electrophoresis 3 months → urine 24h protein Annually → skeletal survey PRN → bone marrow Supporting care Pain management → analgesics, avoid NSAIDs (renal dysfunction), Bone pain → radiation, bisphosphonates Hypercalcemia → bisphosphonates, hydration, steroids Fatigue → anemia (transfuse PRBCS) Drugs that are used (based on the induction protocol i found) For each drug i found a patient handout that has information on the drug, tests needed, interactions, risk factors (ex. fertility), side effects, when to seek help, etc. Bortezomib IV use only ** (other routes are fatal) http://www.bccancer.bc.ca/drug-databasesite/Drug%20Index/Bortezomib_handout_1Dec2013.pdf Dexamethasone Cyclophosphamide http://www.bccancer.bc.ca/drug-databasesite/Drug%20Index/CyclophosphamideIV_handout_20Feb08.pdf **Lots of info taken for patho from: https://www.youtube.com/watch?v=ghvoKhpAc64&t=232s Not scholarly but the rubric doesn’t mark on references, so I am planning on just referencing https://ebookcentral-proquest-com.ezproxy.lib.ucalgary.ca/lib/ucalgaryebooks/reader.action?docID=3384082 (another potential good resource) since it has hella info. I think references at the end of her slides are mostly enough since I wasted some time tryna find resources when those work fine. I think if we were to do a case study just like the guest presenter did in the peds lecture it would hit the criteria for ‘involving the class’ as well as burning some of the 25min. Cus during the case study we could involve the audience, asking questions as we reveal a fake patient scenario. Also if u guys think of any or find any handouts/ useful vids / chemo protocols that would be awesome for this. I think a handout on a chemo protocol for the audience to follow along while we talk about chemo/tx since it’d be too small to display on the board would be one good handout -kalen I found a chemotherapy protocol for MM from BC Cancer (assuming its the same in AB) lmk what you guys think! http://www.bccancer.bc.ca/chemotherapy-protocolssite/Documents/Lymphoma-Myeloma/MYBORPRE_Protocol.pdf I also found this powerpoint with lots of information from BC Cancer as well and it has case studies attached that we could use http://www.bccancer.bc.ca/family-oncologynetworksite/Documents/FPON%20Myeloma%20Sept%202016%20%28greg%20dueck%29.pdf This one has information from diagnosis, staging, treatment, assessment, and follow up http://www.bccancer.bc.ca/health-professionals/clinical-resources/cancer-managementguidelines/lymphoma-chronic-leukemia-myeloma/multiple-myeloma alexa Also: Should be important to touch on Adoptive T-Cell therapy in a segment that discusses where MM is heading. Topics to hit from the outline: 1. Overview of Disease Process Pretty much done, prob just touch on extranodal/intranodal primary tumours 2. Brief overview of treatment regimen (and two supporting meds/tx): Bortezomib & cyclophosphamide Supporting - dexamethasone, bisphosphonates Touch on Adoptive T-Cell Therapy 3. How would we perform patient teaching on one aspect of the disease and/or treatment regimen? (consider demonstrating using a case study or roleplaying): We will do a case study. Case study found on powerpoint or drug teaching from handouts found 4. Two CANO standards (how are we addressing them in practice when caring for a patient with this treatment plan & diagnosis?): I attached the list of them below but maybe - supportive therapeutic relationship and individualized and holistic care?
