IMWG consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation
This abstract provides a comprehensive overview of the management of multiple myeloma in patients who are not eligible for autologous stem-cell transplantation. It emphasizes the importance of early treatment initiation for patients with symptomatic disease and organ damage, such as hypercalcemia, renal failure, anemia, or bone lesions. The International Staging System and chromosomal abnormalities are discussed as valuable tools for risk stratification and treatment decision-making. The document highlights the use of various active agents in the treatment of MM, including proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents. These agents have shown efficacy in improving overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) in this patient population. Additionally, the document addresses the importance of assessing and managing concomitant diseases, frailty, or disability in MM patients. Reduced-dose approaches are recommended for patients with comorbidities or limitations in mental or mobility functions. Supportive care is highlighted as an integral part of MM management, with a focus on addressing complications such as bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy. Prompt intervention and appropriate management of these complications are crucial for optimizing patient outcomes. Overall, this abstract serves as a valuable resource for clinicians in guiding the management of MM in patients who are not eligible for autologous stem-cell transplantation. It provides evidence-based recommendations for treatment selection, risk stratification, and supportive care, ultimately aiming to improve patient outcomes and quality of life.
Important Points:
- Thalidomide-based regimens, such as thalidomide combined with dexamethasone (TD), have shown superiority over high-dose dexamethasone for partial response and time to progression, but are more toxic.
- Bortezomib-based regimens, such as bortezomib-melphalan-thalidomide (VMP), significantly increase complete response, time to progression, and overall survival compared to standard melphalan-prednisone (MP) regimens.
- Lenalidomide-based regimens, such as lenalidomide plus low-dose dexamethasone (Rd), are better tolerated than lenalidomide plus high-dose dexamethasone (RD) and show a significant survival benefit.
- Fit patients can receive full-dose therapy with options like MPT, VMP, Rd, VMPT-VT, and MPR-R.
- MPT may be preferred for its oral administration and lower cost.
- VMP and VMPT-VT or VCD and VRD may be preferred in patients who need rapid, profound cytoreduction.
- Rd or MPR-R may be preferred when oral administration and the lack of peripheral neuropathy are major considerations.
- Unfit patients should receive reduced-dose MPT or VMP or two-drug combinations with bortezomib or lenalidomide and low-dose dexamethasone.
- Maintenance therapy with thalidomide, lenalidomide, or bortezomib can prolong progression-free survival, but the impact on overall survival is inconsistent.
- Repeating the same treatment is recommended for patients with a durable response, while alternative regimens are suggested for those with short-term remission duration or progression during initial therapy.
- Standard treatments for relapsed disease include bortezomib or lenalidomide combined with dexamethasone or bortezomib-pegylated liposomal doxorubicin.
- The diagnostic process aims to distinguish between different plasma cell diseases based on the IMWG criteria, including monoclonal gammopathy of undetermined significance, asymptomatic (smoldering) MM, symptomatic MM, solitary plasmacytoma, and other plasma cell diseases.
- Symptomatic MM is defined as the presence of 10% clonal bone marrow plasma cells and organ damage (CRAB): hypercalcemia, renal failure, anemia, or bone lesions.
- The diagnostic work-up for MM includes history and physical examination, blood and urine tests, bone marrow aspiration and biopsy, and imaging studies such as skeletal survey.
- The International Staging System (ISS) is used to assess the prognosis of patients with symptomatic MM, with stage III associated with poor prognosis.
- Chromosomal abnormalities, such as t(4;14), t(14;16), and t(14;20), are associated with poor prognosis, while hyperdiploidy, t(11;14), and t(6;14) are considered standard-risk features.
- Close monitoring is suggested every 1 to 3 months for asymptomatic patients, while immediate treatment is required for patients with active and symptomatic MM.
- Second-line treatment is indicated for clinical relapse or significant and rapid increase in paraprotein levels.
- The assessment of organ function, comorbidities, frailty, and disability should be considered to define patients' status and guide treatment decisions.
- Patients with multiple myeloma should be referred to specialized units with MM experts for optimal care.
- Palliative care is important for patients when cure is no longer achievable, and counseling by a palliative specialist is suggested.
- Treatment of pain in multiple myeloma should start with nonopioid analgesic agents, with weak or stronger opioid analgesics introduced if necessary.
- The International Staging System is used to classify multiple myeloma into three stages based on serum 2-microglobulin levels and serum albumin levels.
- The document emphasizes the use of active agents such as proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents for the treatment of multiple myeloma.
- Concomitant diseases, frailty, or disability should be assessed and managed, with reduced-dose approaches considered if necessary.
- Supportive care is crucial in managing complications such as bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy.
- The document provides evidence-based recommendations for treatment selection, risk stratification, and supportive care to improve patient outcomes and quality of life.
- Multiple myeloma (MM) management in patients not eligible for autologous stem-cell transplantation.
- Immediate treatment required for patients with symptomatic disease and organ damage.
- Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are active agents for treatment.
- Assessment and management of concomitant diseases, frailty, or disability.
- Supportive care for complications such as bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy.
- Recommendations for reduced-dose approaches in patients with limitations.
- Emphasis on early intervention and prompt management of complications.
- Aim to improve overall survival, progression-free survival, and event-free survival.
- Evidence-based recommendations for treatment selection and supportive care.
Authors:
Palumbo A, Rajkumar SV, San Miguel JF, Larocca A, Niesvizky R, Morgan G, Landgren O, Hajek R, Einsele H, Anderson KC, Dimopoulos MA, Richardson PG, Cavo M, Spencer A, Stewart AK, Shimizu K, Lonial S, Sonneveld P, Durie BG, Moreau P, Orlowski RZ
Citation:
J Clin Oncol. 2014;32(6):587-600.
doi:10.1200/JCO.2013.48.7934