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Multiple myeloma.pptx

  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
  4. 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
  5. • 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
  6. • 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
  7. 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.
  8. • 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
  9. Multiple Myeloma DEVITA
  10. Treatment options Old regimen Dexamethasone Vincristine Adriamycin Dexamethasone VAD regimen Novel agents Bortezomib Lenalidomide Dexamethasone Carflizomib Daratumumab
  11. Bortezomib(velcade) Intravenous/subcutaneous
  12. Vd vs VAD
  13. (ENDURANCE E1A11) • bortezomib/lenalidomide/dexamethasone vs carfilzomib/lenalidomide/dexamethasone as induction therapy
  14. Response To Induction
  15. • 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
  16. • 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
  17. 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
  18. 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)
  19. • 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
  20. • 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
  21. 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
  22. Preffered Other recommended Useful Study about that
  23. 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
  25. 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
  26. 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
  27. 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
  28. • 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
  29. 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
  30. • 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
  31. • 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.
  32. 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
  33. • 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.
  34. 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
  35. 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
  36. HYPERCALCEMIA • Hydration, bisphosphonates (zoledronic acid preferred), denosumab, steroids, and/or calcitonin are recommended HYPERVISCOSITY  Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity
  37. 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
  38. • 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
  39. • VENOUS THROMBOEMBOLISM (VTE) • Aspirin 81–325 mg once daily • Rivaroxaban 10 mg daily • LMWH
  40. 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
  41. • 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
  42. questions • A patient diagnosed with MGUS low risk.the absolute risk of 20 year progression A. 2% B. 5% C. 10% D. 15%
  43. • Dose of RT in solitary plasmacytoma A. 45-55gy B. 40-50gy C. 45-50gy D. 35gy
  44. • most appropriate Treatment of transplant eligible MM patient A. Borte+lenid+dexa B. Borte+dexa C. Linid+dexa D. All of above
  45. • Regimen used for primary amyloidosis A. Borte+lenid+dexa B. borte+cyclophosphamide+dexa C. Daratumumab +lenid+dexa D. Borte+dexa 
  46. • 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 ?

Editor's Notes

  1. D-dexa d1-4,9-12,17-20,,,d dexa-d1,d8.d15,d22 =4 weekly cycles linid 25mg d1 to d21