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    Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Multiple Myeloma

    Initial Evaluation

    The initial approach to the patient is to evaluate the following parameters:

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    1. Detection of a monoclonal (or myeloma) protein (M protein) in the serum or urine.
    2. Detection of more than 10% of plasma cells on a bone marrow examination.
    3. Detection of lytic bone lesions or generalized osteoporosis in skeletal x-rays.
    4. Presence of soft tissue plasmacytomas.
    5. Serum albumin and beta-2-microglobulin levels.
    6. Detection of free kappa and free lambda serum immunoglobulin light chain.[1]

    Treatment selection is influenced by the age and general health of the patient, prior therapy, and the presence of complications of the disease.[2]

    Induction Therapy

    The choice of induction therapy is unclear at the present time; however, the current basic categories include the use of steroids, thalidomide, lenalidomide, bortezomib, and alkylating agents, often in combination.[3]

    Several questions are raised when therapy is being chosen for a patient with symptomatic myeloma at first presentation, including the following:

    1. Is the patient eligible for a clinical trial? The sequence and combinations of new and older therapies can only be determined by prospective clinical trials.
    2. Is autologous stem cell transplantation (ASCT) a possible consolidation option for this patient? If so, alkylating agents should be avoided during induction therapy to avoid compromise of stem cell collection and to lessen leukemogenic risk.
    3. Does the patient have comorbidities? Age, organ dysfunction, and risk of cardiovascular and thrombotic complications would influence the choice of induction therapies as well as the choice of whether to consider consolidation therapies.

    Induction therapy agents

    Multiple therapeutic agents are available for induction therapy, either alone or in combinations.[4] These include the following:

    • Steroids (e.g., dexamethasone and prednisone).
    • IMiDs (immunomodulatory drugs).
      • Thalidomide.
      • Lenalidomide.
      • Pomalidomide.
    • Proteasome inhibitors.
      • Bortezomib.
      • Carfilzomib.
    • Alkylating agents (e.g., melphalan and cyclophosphamide).
    • Other cytotoxic drugs (e.g., vincristine, doxorubicin, and liposomal doxorubicin).

    Clinical trials are needed to establish the regimens with the best efficacy and least long-term toxicity. (Refer to the Combination therapy section of this summary for a list of current clinical trials.)

    Guidelines for choosing induction therapy

    Until results become available, outside the context of a clinical trial, clinicians may choose induction therapy based on the following guidelines:

    1. In patients younger than 70 years, alkylators are avoided up front to avoid stem cell toxicity with subsequent risks for cytopenias, secondary malignancies, or poor stem cell harvesting if transplantation is considered for consolidation therapy.[5]
    2. Bortezomib or lenalidomide is combined with dexamethasone for at least 8 months or until best response if consolidation therapy is planned.[6,7] (Refer to the Lenalidomide and Bortezomib sections of this summary for more information.)
    3. The choice of bortezomib or lenalidomide is based on side-effect profile and route of administration.
      • Bortezomib is given in frequent intravenous doses and can cause significant neuropathic toxicities.[7,8,9] Bortezomib is preferred in the setting of renal impairment.[10]
      • Lenalidomide is given orally and can cause an increased risk for deep venous thrombosis (DVT), requiring additional prophylactic medication.[6,11]
    4. Patients with standard-risk disease, as defined in the Stage Information About Plasma Cell Neoplasms section of this summary, might receive induction therapy alone, followed by careful observation after best response.[12]
    5. Patients with high-risk disease might receive induction therapy until best response, followed by consolidation therapy with allogeneic or ASCT.[12]
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