Treatment of Multiple Myeloma(beta)
Patients should be referred to a transplant center to determine transplant eligibility.
Lenalidomide maintenance therapy should be routinely offered to standard-risk patients starting at approximately day 90 to 110 at 10 to 15 mg daily until progression. A minimum of 2 years of maintenance therapy is associated with improved survival, and efforts to maintain therapy for at least this duration are recommended.
The quality and depth of response should be assessed by International Myeloma Working Group (IMWG) criteria.
The goal of initial therapy for transplant-eligible patients should be achievement of the best depth of remission. MRD-negative status has been associated with improved outcomes, but it should not be used to guide treatment goals outside the context of a clinical trial.
It is recommended that depth of response be assessed with each cycle. Frequency of assessment once best response is attained or on maintenance therapy may be assessed less frequently but at minimum every 3 months.
Whole-body low-dose computed tomography (CT) scan has been shown to be superior to skeletal survey done with plain x-rays and is the preferred method for baseline and routine bone surveillance. Fluorodeoxyglucose positron emission tomography/CT and/or magnetic resonance imaging may be used as alternatives at baseline. They may also be used in select situations (e.g. risk-stratifying smoldering myeloma, for monitoring response of nonsecretory and oligosecretory myeloma, and if CT or skeletal survey is inconclusive).
Initial treatment recommendations for patients with multiple myeloma who are transplant ineligible should be individualized based on shared decision making between physicians and patients. Multiple factors should be considered; disease-specific factors such as stage and cytogenetic abnormalities, and patient-specific factors including age, comorbidities, functional status, frailty status, and patient preferences should also be considered.
Physicians/patients should balance the potential improvement in response and disease control with a possible increase in toxicity. Initial dosing should be individualized based on patient age, renal function, comorbidities, functional status, and frailty status. Subsequent dosing may be tailored based on initial response and tolerability.
The goal of initial therapy for transplant-ineligible patients should be achievement of the best quality and depth of remission.
Depth of response for all patients should be assessed by IMWG criteria regardless of transplant eligibility.
There is insufficient evidence to support change in type and length of therapy based on depth of response as measured by conventional IMWG approaches or MRD.
Upon initiation of therapy, one should define patient-specific goals of therapy. Quality-of-life assessment (including symptom management and tolerability of treatment) should be assessed at each visit to determine if the goals of therapy are being maintained/met, and this should influence the intensity and duration of treatment. Redefining the goals prospectively, based on response, symptoms, and quality of life, is recommended.
It is recommended that patients be monitored closely with consideration of dose modifications based on levels of toxicity, neutropenia, fever/infection, tolerability of adverse effects, performance status, liver and kidney function, and in keeping with the goals of treatment.
Treatment of biochemically relapsed myeloma should be individualized. Factors to consider include patient’s tolerance of prior treatment, rate of rise of myeloma markers, cytogenetic risk, presence of comorbidities (i.e., renal insufficiency), frailty, and patient preference. High-risk patients as defined by high-risk cytogenetics and early relapse post-transplant/initial therapy should be treated immediately. Close observation is appropriate for patients with slowly progressive and asymptomatic relapse.
All clinically relapsed patients with symptoms due to myeloma should be treated immediately.
Triplet therapy should be administered on first relapse, though the patient’s tolerance for increased toxicity should be considered. A triplet is defined as a regimen with two novel agents (PIs, immunomodulatory drugs, or monoclonal antibodies).
Treatment of relapsed multiple myeloma may be continued until disease progression. There are not enough data to recommend risk-based versus response-based duration of treatment.
Prior therapies should be taken into consideration when selecting the treatment at first relapse. A monoclonal antibody-based regimen in combination with an immunomodulatory drug and/or PI should be considered. Triplet regimens are preferred based on tolerability and comorbidities.
The risk status of the patients should be assessed using the Revised International Staging System for all patients at the time of diagnosis.
Repeat risk assessment at the time of relapse should be performed and should include bone marrow with fluorescence in situ hybridization for myeloma abnormalities seen with progression, including 17p and 1q abnormalities. Fluorescence in situ hybridization for primary abnormalities (translocations and trisomies), if seen in the initial diagnostic marrow, does not need to be repeated.
The IMWG revised response criteria should be used for response assessment.
All measurable parameters need to be followed, including light and heavy chain analysis.
All responses excluding marrow and imaging should be confirmed as per IMWG criteria.
How strong is the ASCO's recommendation?