Treatment Multiple Myeloma

Symptomatic/progressive myeloma: Systemic therapy - to control progression of myeloma Supportive care - to prevent serious from the complications of the disease *Initial standard treatment for newly diagnosed myeloma depends on whether or not the patient is a candidate for high dose chemotherapy with autologous stem cell transplant. Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.705

DrugsDose regimen 1. Dexamethasone alone40 mg for 4 days every 2 weeks 2. VAD chemotherapy Vincristine Doxorubicin Dexamethasone 0.4 mg/d in a 4-day continuous infusion 9mg/m2 per day in a 4-day continuous infusion 40 mg for 4 days per week for 3 weeks 3. Thalidomide + dexamethasone 200 mg PO phs 40 mg for 4 days every 2 weeks Transplant Candidates Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.705

Non – Transplant Candidates DrugsDose regimen 1.MP Melphalan Prednisone 8 mg/m 2 /day mg/m 2 /day for 4 days 2. MPT Melphalan Prednisone Thalidomide Given 4-7 days every 4-6 weeks Patients responding to therapy generally have a prompt and gratifying reduction in bone pain, hypercalcemia, and anemia, and fewer infections Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.705

High Dose Melphalan Therapy with hematopoietic stem cell support – can achieve high overall response rates and prolonged progression-free and overall survival – Two successive HDTs (tandem transplants) are more effective than single HDT in patients who don,t achieve a complete or very good partial response to the first transplant Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.705

Maintenance Therapy No standard maintenance therapy to prolong time to progression IFN - has modest benefit but has significant side effects Oral prednisone - effective in a single trial Ongoing studies : thalidomide and lenalidomide to prolong progression-free survival post-transplant. Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.705

Relapse Lenalidomide and/or bortezomib – Used to treat relapsed myeloma – target not only the tumor cell but also the tumor cell–bone marrow interaction and the bone marrow milieu – In combination with dexamethasone 60% partial responses and 10–15% complete responses Thalidomide -if not used as initial therapy, can achieve responses in refractory cases. High-dose melphalan and stem cell transplant -if not used earlier, also have activity in patients with refractory disease. Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.705

Major Causes of Death *Median overall survival : 5–6 years 1.progressive myeloma 2.renal failure 3.Sepsis 4.therapy-related acute leukemia or myelodysplasia Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.706

Supportive Care directed at the anticipated complications Hypercalcemia  generally responds well to bisphosphonates (pamidronate 90 mg or zoledronate 4 mg once a month), glucocorticoid therapy, hydration, and natriuresis.  Calcitonin - adds to the inhibitory effects of glucocorticoids on bone resorption. Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.706

Iatrogenic worsening of renal function  prevented by maintaining a high fluid intake to prevent dehydration and to help excrete light chains and calcium  acute renal failure: plasmapheresis Urinary tract infections : watched for and treated early. Supportive Care Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.706

Hyperviscosity Syndromes: Plasmapheresis (treatment of choice) Recurrent serious infections: Prophylactic administration of IV globulin preparations Anemia  responds to erythropoietin along with hematinics (iron, folate, cobalamin) Supportive Care Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.706

Neurologic symptoms in the lower extremities, severe localized back pain, or problems with bowel and bladder control  emergency MRI and radiation therapy for palliation Bone lesions  respond to analgesics and chemotherapy Supportive Care Reference: 17 th Ed. Harrison’s Principles of Internal Medicine p.706