INTRODUCTION — Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. This clone of plasma cells proliferates in the bone marrow and often results in extensive skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures. Additional disease-related complications include hypercalcemia, renal insufficiency, anemia, and infections.
The International Myeloma Working Group has developed uniform response criteria, which are used to measure the effect of treatment. These criteria are described in detail here. This same group has proposed definitions of survival endpoints (ie, progression-free survival, time to progression, and duration of response) to be used in reporting clinical research. These are also defined here.
The following issues related to MM are discussed separately:
●The diagnosis of MM and the tests used to measure monoclonal proteins in the blood and urine. (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis" and "Laboratory methods for analyzing monoclonal proteins".)
●Indications for the treatment of MM, risk stratification, and the choice of initial therapy based on this risk stratification and patient characteristics. (See "Multiple myeloma: Overview of management" and "Multiple myeloma: Initial treatment" and "Multiple myeloma: Treatment of first or second relapse".)
●Disease-related and treatment-related complications and the use of bisphosphonates in patients with MM. (See "Multiple myeloma: Overview of management", section on 'Prevention and management of complications' and "Multiple myeloma: The use of osteoclast inhibitors".)
RESPONSE ASSESSMENT — Patients should be evaluated before each treatment cycle to determine how their disease is responding to therapy and to assess for potential treatment-related and disease-related complications (table 1).
Clinical assessment — Prior to each treatment cycle, patients should be asked how they are tolerating therapy and evaluated for signs and/or symptoms of treatment- and disease-related complications, including:
●Anemia
●Hypercalcemia
●Renal insufficiency
●Infection
●Skeletal lesions
●Extramedullary plasmacytomas
●Thrombosis
●Neuropathy
●Hyperviscosity syndrome (eg, oronasal bleeding, blurred vision, headaches, dizziness)
At each visit, we perform a directed history and physical examination, complete blood count with differential, a chemistry screen that includes measurements of serum creatinine and calcium, and myeloma-specific tests discussed below. (See 'Choice of test(s)' below.)
The management of treatment- and disease-related complications is discussed separately. (See "Multiple myeloma: Overview of management", section on 'Prevention and management of complications'.)
Assessing tumor burden
Choice of test(s) — We assess tumor burden prior to each treatment cycle. The preferred method for a given patient depends on the results of baseline studies and on the suspected degree of response (table 1) [1]:
●Measurable M protein – Most patients will have a serum monoclonal (M) protein level ≥1 g/dL and/or urine M protein level ≥200 mg/day at baseline (ie, measurable M protein). In such patients, baseline tumor burden is measured prior to therapy using the serum protein electrophoresis (SPEP), 24-hour urine protein electrophoresis (UPEP), and the serum free light chain (FLC) assay. At follow up, prior to each cycle of therapy, tumor burden is measured using the SPEP and either the serum FLC assay or the UPEP. Many patients and clinicians find the serum FLC assay to be more convenient than the UPEP, although the correlation between these tests is not perfect. In patients followed preferentially with SPEP and serum FLC assay, the UPEP should still be performed periodically (eg, every six months) for validation and to check for other renal issues such as albuminuria. Serum and urine immunofixation should be done in addition, once the electrophoresis shows no measurable protein. In these patients, other methods for measuring tumor burden (eg, bone marrow biopsy, whole body positron emission tomography-computed tomography [PET/CT]) are reserved for the investigation of suspected complete response or progressive disease. (See 'SPEP, UPEP, and immunofixation' below.)
●No measurable M protein, measurable FLC – A subset of patients without measurable M protein in serum or urine at baseline will have an involved serum FLC level ≥10 mg/dL (ie, measurable FLC). In such patients, FLC levels are used as the primary measure of tumor burden with each cycle of therapy. (See 'Free light chain assay' below.)
●No measurable M protein or FLC – A minority of patients will have no measurable M protein or involved immunoglobulin FLC at baseline, yet demonstrate ≥30 percent plasma cells on bone marrow evaluation. In such patients, tumor burden is assessed by periodic bone marrow aspirate and biopsy. PET/CT may also be of value in following these patients [2]. The frequency of bone marrow and PET/CT assessment in these patients depends on other clinical parameters (eg, hemoglobin, calcium, and creatinine); patients who are felt to be responding well based on improvement in end-organ function will need bone marrow and imaging assessments less frequently compared with those in whom the response status is less clear. (See 'Bone marrow aspirate and biopsy' below.)
Although not readily available at most centers, mass spectrometry can quantitate low level M proteins and studies are evaluating whether it can be used to follow disease activity in a subset of these patients [3]. (See "Laboratory methods for analyzing monoclonal proteins", section on 'Mass spectrometry'.)
●Plasmacytoma – Rarely, patients with no M protein or FLC measurable and <30 percent plasma cells on bone marrow evaluation will have biopsy-proven plasmacytoma. If such patients have at least one lesion on whole body PET/CT that has a single diameter of ≥2 cm, tumor burden can be followed with whole body PET/CT every three to four cycles until a plateau or complete response is attained. (See 'Imaging' below.)
●Suspected complete response – When a complete response (CR) is suspected, the standard evaluation includes SPEP, serum immunofixation, 24-hour UPEP, urine immunofixation, and serum FLC. Urine immunofixation may not be necessary in the CR evaluation of patients with measurable serum M protein at diagnosis. In one study of patients achieving negative serum immunofixation, the urine immunofixation was also negative in all of the patients with serum M protein only at diagnosis and 98.6 percent of those with serum and urine M protein at diagnosis [4]. Although urine immunofixation to document CR can be omitted in patients who are not on clinical trials, it is still required for patients on clinical trials to document CR in accordance with the International Myeloma Working Group (IMWG) criteria. In clinical trials, a bone marrow aspirate and biopsy is needed to document a CR. Assessment of the bone marrow for minimal residual disease (MRD) using next-generation flow cytometry or next-generation sequencing is usually reserved for patients on clinical trials. In patients who are suspected to be MRD negative, cross-sectional imaging (eg, a whole body PET/CT) may be needed to document imaging MRD-negative status in clinical trials [1]. (See 'Imaging' below and 'Minimal residual disease assessment' below.)
●Suspected progression – An evaluation at the time of suspected disease progression based on clinical or biochemical findings should include SPEP, serum immunofixation, 24-hour UPEP, serum FLC, hemoglobin, serum calcium, and creatinine. In addition, imaging studies such as PET/CT, MRI, or whole body low dose CT may be needed [5]. A bone marrow aspirate and biopsy is not always necessary, but should be performed if there is doubt about the disease status, to determine if change in the cytogenetic characteristics has occurred, or to determine eligibility for clinical trials.
SPEP, UPEP, and immunofixation — The measurement of M protein in the serum and urine is the preferred method to determine disease response and monitor for relapse. This approach can be used for patients with a serum M protein level ≥1 g/dL and/or urine M protein level ≥200 mg/day at baseline (ie, measurable M protein).
●Serum M protein is quantified using densitometry on SPEP. (See "Laboratory methods for analyzing monoclonal proteins", section on 'Serum protein electrophoresis (SPEP)'.)
●Urine M protein is quantified using densitometry on 24-hour UPEP. (See "Laboratory methods for analyzing monoclonal proteins", section on '24-hour urine protein electrophoresis (UPEP)'.)
●Serum and urine immunofixation are used once the electrophoresis shows no measurable protein. Immunofixation is more sensitive than protein electrophoresis, but cannot estimate the size of the M protein. (See "Laboratory methods for analyzing monoclonal proteins", section on 'Serum immunofixation' and "Laboratory methods for analyzing monoclonal proteins", section on 'Urine immunofixation'.)
Both serum and urine M protein measurements are used to follow all patients, because some patients who had positive serum studies on presentation will only show light chains on UPEP at the time of relapse. This is called "light chain or Bence Jones escape" [6,7].
An FLC assay may also detect light chains at the time of relapse and some experts have suggested that serial FLC measurements may be used to assess response in place of 24-hour urine studies. In clinical practice this is reasonable, provided periodic UPEP studies are done for verification. In clinical trials, the UPEP is still needed for all patients with measurable disease.
Daratumumab and isatuximab are immunoglobulin G (IgG) kappa monoclonal antibodies that can be detected on SPEP and immunofixation assays. As such, they may obfuscate the response assessment in patients with IgG kappa myeloma protein. A daratumumab-specific immunofixation electrophoresis reflex assay has been developed [8]. This assay uses a murine anti-daratumumab antibody to shift the migration of daratumumab on electrophoresis to allow for differentiation between it and native IgG kappa.
Free light chain assay — Serum FLC measurement can be used to monitor tumor burden in patients without measurable M protein in the serum and urine [9]. It also provides a more rapid way to evaluate response to treatment in patients with abnormal baseline FLC, because of its significantly shorter half-life than the monoclonal IgG or IgA. However, not all patients need FLC monitoring:
●FLC levels are most informative in patients who lack measurable M protein in the serum and urine (ie, serum M protein <1 g/dL and urine M protein <200 mg/day). FLC assays are also useful in clinical practice as an alternative to the UPEP in patients with measurable M protein levels.
●FLC levels can be used only if the following two criteria are met:
•Baseline FLC ratio is abnormal (<0.26 or >1.65)
•Baseline level of the involved light chain isotype (kappa or lambda) is ≥10 mg/dL. In patients with a FLC kappa/lambda ratio <0.26, lambda is the "involved" light chain and kappa is the "uninvolved" light chain. Conversely, in patients with an FLC ratio of >1.65, kappa is the "involved" light chain and lambda is the "uninvolved" light chain.
In patients achieving CR, the prognostic impact of an abnormal FLC ratio is maintained even when flow cytometry is unable to detect clonal bone marrow plasma cells (ie, MRD-negative cases) [10]. An important exception is that an abnormal FLC ratio solely due to suppression of one or both light chains (eg, secondary to treatment) does not appear to impact prognosis.
Further discussion on the use of FLC measurement in plasma cell disorders is presented separately. (See "Laboratory methods for analyzing monoclonal proteins", section on 'Serum free light chains'.)
Bone marrow aspirate and biopsy — A small subset of myeloma patients lack measurable M protein in the serum and urine, and also have either a normal FLC ratio or involved FLC level <10 mg/dL. Periodic bone marrow aspirate and biopsy plays a key role in the response assessment of these patients. In order to follow disease activity, the baseline bone marrow plasma cell percentage must be significant, typically ≥30 percent. In addition, a bone marrow assessment is required for the determination of CR.
When using bone marrow to assess response, the percentage of plasma cells is usually determined by a morphologic evaluation and visual quantitation.
The importance of including a bone marrow examination in the accurate estimation of CR rates was perhaps best demonstrated in a study of 92 patients with previously measurable disease who had achieved negative serum and urine immunofixation following treatment [11]. After evaluation of a bone marrow biopsy, 79 patients (86 percent) demonstrated less than 5 percent plasma cells, while 13 patients (14 percent) had 5 percent or greater plasma cells, 11 of whom demonstrated monoclonality. When only patients with a normal serum FLC ratio and negative immunofixation of the urine and serum were analyzed, 3 of 26 patients (10 percent) demonstrated 5 percent or greater plasma cells in the bone marrow.
While generally reserved for the research setting, quantitative assessment of MRD in the bone marrow may also be performed using next-generation sequencing or next-generation flow cytometry. The clinical value of these more sensitive tests is yet to be determined, but is an area of active research. (See 'Minimal residual disease assessment' below.)
Imaging — Imaging with a whole body combined 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) is part of the assessment of suspected CR and used in the evaluation of response in patients with extramedullary plasmacytoma [1,5].
The PET component provides a measure of tumor burden (including extramedullary sites) through tumor metabolic activity, while the CT component localizes the metabolic activity and is a sensitive measure of bone lesions. Numerous studies have demonstrated the value of PET in assessing treatment response during therapy [2,12-17].
The International Myeloma Working Group response criteria defines a negative whole body PET/CT as the disappearance of every area of increased tracer uptake found at baseline, or on a preceding PET/CT; or a decrease to less than the mediastinal blood pool standardized uptake value (SUV); or a decrease to less than that of surrounding normal tissue [1]. Initial studies suggest that background liver activity (ie, Deauville criteria) may be used as a comparison to define response in the bone marrow and focal lesions [18]. Validation in additional cohorts is needed before applying this measure in standard practice.
Studies suggest that magnetic resonance imaging (MRI) is more sensitive than PET when used for initial staging; however, MRI appears to have a higher false positive rate than PET when used for response assessment, partially due to its inability to distinguish between bone remodelling versus residual disease in this setting [2,16,19-22]. MRI is slower to normalize following treatment. Ongoing studies are evaluating the use of PET/MRI for response assessment [23].
Minimal residual disease assessment — We typically reserve MRD assessment for patients on clinical trials [1]. MRD status is prognostic, and has been proposed as a surrogate marker for progression-free survival (PFS) and overall survival (OS) in clinical trials. However, its clinical use outside of trials is unclear as it does not yet inform treatment decisions.
Interpretation of studies evaluating MRD is complicated by heterogeneity in the methods used, timing of samples, and reported outcomes. The most robust data come from bone marrow samples; peripheral blood assays need further validation.
There are two main techniques, each of which has strengths and weaknesses [1,24]:
●Next-generation flow cytometry – A method standardized by the EuroFlow consortium can be performed in a few hours using automated software that minimizes subjectivity. A baseline sample is not required, but the study must be performed on a fresh sample.
●Next-generation VDJ sequencing – One assay using this method, the ClonoSEQ assay, has been US Food and Drug Administration approved for MRD assessment in myeloma. A baseline sample is required to identify the dominant clonotype, but the study can be performed on both fresh and stored samples. It is not impacted by therapeutic monoclonal antibodies.
Mass spectrometry is also being evaluated in this setting, although it is less widely available [25].
Meta-analyses of prospective studies using different MRD assessment techniques have demonstrated an association between achieving undetectable MRD and improved PFS and OS [26-29]. As an example, a meta-analysis combined data from >2500 patients enrolled on four phase 3 trials that used next-generation sequencing on bone marrow to assess MRD (POLLUX, CASTOR, ALCYONE, and MAIA) [27]. Patients who achieved a CR or better with undetectable MRD had superior PFS when compared with patients who did not achieve a CR and/or had detectable MRD (estimated 48-month PFS 70 versus 24 percent; HR 0.20; 95% CI 0.16-0.24). When the analysis was limited to patients with a CR or better, achieving undetectable MRD improved PFS over that seen in patients with detectable MRD (estimated 48-month PFS 70 versus 52 percent; HR 0.52, 95% CI 0.41-0.66).
The prognostic value of MRD status may differ according to the duration of response and aggressiveness of disease. Some studies suggest that the magnitude of PFS benefit may be even greater when undetectable MRD status is sustained over 6 to 12 months, and that reemergence of MRD may predict clinical relapse [30,31]. Others suggest that patients with more indolent disease may have good long-term disease control despite having detectable MRD [32].
While patients with undetectable MRD do better than those with detectable MRD, it is not known whether altering therapy based on MRD status will improve outcomes. As always, one must be careful when interpreting studies that show improved outcome in responders versus nonresponders (eg, detectable MRD versus undetectable MRD) since such comparisons have inherent methodologic flaws that cannot be overcome by increasing the sample size. In general, whether or not a treatment works, "responders" will typically appear to do better than "nonresponders." One way of overcoming the bias that exists when comparing responders with nonresponders is to perform landmark analysis at time points that ensure that almost all patients have had time to reach the response level being studied.
Several trials are investigating the use of MRD to guide treatment decisions (eg, escalation and deescalation of care). As we await results, MRD status cannot drive decisions on whether to continue, alter, or resume therapy. MRD negativity is also not indicative of cure. A subset of patients with sustained MRD negative status for a prolonged period of time may be cured, but longer follow-up of patients in clinical trials is needed to confirm this hypothesis.
In the future, the preferred test for MRD detection, optimal timing of assessment, and the best MRD threshold to use will likely vary depending on availability and the reason MRD is being measured (eg, prognostic marker, goal of therapy, indicator of cure).
RESPONSE CRITERIA
IMWG response categories — The International Myeloma Working Group (IMWG) uniform response criteria are the preferred criteria to determine the patient's best response to treatment and to define when a relapse has occurred (table 2) [1,33,34]:
●Minimal residual disease (MRD) negative – Absence aberrant clonal plasma cells by next-generation flow cytometry or next-generation sequencing on bone marrow aspirates with a minimum sensitivity of 1 in 105 nucleated cells or higher.
●Stringent complete response (sCR) – In addition to CR criteria (defined below), these patients have a normal free light chain (FLC) ratio and have no clonal cells by bone marrow immunohistochemistry or immunofluorescence. The latter is achieved if there is a kappa/lambda ratio of ≤4:1 or ≥1:2 after examination of a minimum of 100 plasma cells.
●Complete response (CR) – Absence of monoclonal (M) protein in serum and urine by immunofixation with no current evidence of soft tissue plasmacytoma. In addition, bone marrow aspirate and biopsy must demonstrate less than 5 percent clonal plasma cells. In patients who lack measurable M proteins in the serum and urine being monitored using the FLC levels, the definition of CR requires a normalization of the FLC ratio in addition to the above criteria [35].
●Very good partial response (VGPR) – Serum and urine M protein detectable by immunofixation but not on electrophoresis or at least a 90 percent reduction in serum M protein with a urine M protein <100 mg/24 hours. In patients who lack measurable M proteins in the serum and urine being monitored using the FLC levels, the definition of VGPR requires >90 percent decrease in the difference between involved and uninvolved FLC levels [35].
●Partial response (PR) – ≥50 percent reduction in serum M protein and reduction of 24-hour urinary M protein by 90 percent or to <200 mg/24 hours. In patients who lack measurable M proteins in the serum and urine, the definition of PR requires ≥50 percent decrease in the difference between involved and uninvolved FLC levels. If the FLC levels were also unmeasurable at baseline, a 50 percent reduction in bone marrow plasma cells is acceptable as long as the original bone marrow contained at least 30 percent plasma cells. PR also requires a 50 percent reduction in size of any soft tissue plasmacytomas if present at baseline.
●Minimal response (MR) – ≥25 but ≤49 percent reduction of serum M protein and reduction in 24-hour urine M protein by 50 to 89 percent. If present at baseline, a ≥50 percent reduction in the size of soft tissue plasmacytomas is also required for MR.
●Stable disease (SD) – Does not meet criteria for CR, VGPR, PR, or PD.
●Progressive disease (PD) – 25 percent increase from lowest response value in any of the following:
•Serum M protein (absolute increase must be ≥0.5 g/dL). A serum M protein increase ≥1 g/dL denotes PD, if the lowest M-component was ≥5 g/dL.
•Urine M protein (absolute increase must be ≥200 mg/24 hours).
•Difference in the kappa and lambda FLC (absolute increase must be >10 mg/dL). This FLC criterion should only be used for patients with unmeasurable M protein in the serum and urine.
•Bone marrow plasma cell percentage (absolute increase must be ≥10 percent). This criterion should be used for patients without measurable serum and urine M protein levels and without measurable involved FLC levels.
PD is also diagnosed when there is a ≥50 percent increase in the size or development of new bone lesions or soft tissue plasmacytomas. A clinical relapse can be documented based on the development of one or more of the following attributable to the myeloma: a serum calcium >11.5 mg/dL, decrease in hemoglobin of ≥2 g/dL, rise in serum creatinine ≥2 mg/dL, hyperviscosity related to the serum paraprotein.
All response categories (CR, sCR, VGPR, PR, and PD) require two consecutive assessments made at any time before the institution of any new therapy. However, bone marrow assessments need not be confirmed. CR, sCR, VGPR, PR, MR, and SD categories also require no known evidence of progressive or new bone lesions if radiographic studies were performed. VGPR and CR categories require serum and urine studies regardless of whether disease at baseline was measurable on serum, urine, both, or neither. For PD, serum M-component increases of ≥1 g/dL are sufficient to define relapse if starting M-component is ≥5 g/dL [34].
Renal response — For patients who have myeloma-associated renal impairment at the time of diagnosis, changes in kidney function with treatment should be documented. For those who require dialysis, conversion to dialysis independence is a strong marker of treatment efficacy. The IMWG has proposed the following criteria for renal response in those who are not dialysis-dependent based on baseline estimated glomerular filtration rate (eGFR) and best attained creatinine clearance (CrCl) [36,37]:
●Complete response – Baseline eGFR <50 mL/min/1.73 m2, improved to CrCl ≥60 mL/min
●Partial response – Baseline eGFR <15 mL/min/1.73 m2, improved to 30 to 59 mL/min
●Minor response – Baseline eGFR <15 mL/min/1.73 m2, improved to 15 to 29 mL/min; or baseline eGFR 15 to 29 mL/min/1.73 m2, improved to CrCl 30 to 59 mL/min
The management of kidney impairment in patients with myeloma is discussed separately. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Treatment and prognosis".)
SURVIVAL END POINTS — Retrospective reviews have found that the amount of time that lapses before progression of myeloma may be a stronger predictor of a patient's survival when compared with the depth of their initial response to chemotherapy [38]. Overall survival is markedly shortened for patients who experienced disease progression at 6 or 12 months. The rapidity with which the best response is obtained is also not necessarily a predictor for the duration of the subsequent response.
As the importance of this response time is better understood, the International Myeloma Working Group has proposed uniform definitions of survival end points. Recommended end points are defined as follows [1,33,34]:
●Progression-free survival: Time from start of treatment to disease progression or death from any cause.
●Time to progression: Time from start of treatment to disease progression. Deaths due to causes other than progression are censored, but not included in this calculation.
●Duration of response: For patients who have achieved a partial or greater response, this is the time from when the response was first noted until the time of disease progression. Deaths due to causes other than progression are censored, but not included in this calculation.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Multiple myeloma".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Multiple myeloma treatment (Beyond the Basics)" and "Patient education: Multiple myeloma symptoms, diagnosis, and staging (Beyond the Basics)" and "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)")
●The Basics (see "Patient education: Multiple myeloma (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Clinical assessment – Patients with multiple myeloma (MM) should be evaluated before each treatment cycle to determine how their disease is responding to therapy and to assess for potential treatment- and disease-related complications.
An assessment of treatment- and disease-related complications includes a directed history and physical examination in addition to a complete blood count with differential, and a chemistry screen that includes measurements of serum creatinine and calcium. (See 'Clinical assessment' above.)
●Assessing tumor burden – We assess tumor burden prior to each treatment cycle. The preferred method for a given patient depends on the results of baseline studies and on the suspected degree of response (table 1). (See 'Choice of test(s)' above.)
•Measurable M protein – Most patients will have a serum monoclonal (M) protein level ≥1 g/dL and/or urine M protein level ≥200 mg/day at baseline (ie, measurable M protein). In such patients, baseline tumor burden is measured prior to therapy using the serum protein electrophoresis (SPEP), 24-hour urine protein electrophoresis (UPEP), and the serum free light chain (FLC) assay. At follow up, prior to each cycle of therapy, tumor burden is measured using the SPEP and either the serum FLC assay or the UPEP. In patients followed preferentially with SPEP and serum FLC assay, the UPEP should still be performed periodically (eg, every six months) for validation and to check for other renal issues such as albuminuria. Serum and urine immunofixation are used once the electrophoresis shows no measurable protein. (See 'SPEP, UPEP, and immunofixation' above.)
•No measurable M protein, measurable FLC – A subset of patients without measurable M protein at baseline will have an involved serum FLC level ≥10 mg/dL. In such patients, FLC levels are used as the primary measure of tumor burden with each cycle of therapy. (See 'Free light chain assay' above.)
•No measurable M protein or FLC – Patients without measurable M protein or abnormal FLC can be followed with periodic bone marrow aspirates and biopsies. Whole body FDG PET/CT may also be of value in following these patients. (See 'Bone marrow aspirate and biopsy' above.)
•Suspected complete response – When a complete response (CR) is suspected in clinical practice, the evaluation should include SPEP, serum immunofixation, 24-hour UPEP, urine immunofixation, and serum FLC. Bone marrow aspirate and biopsy and a whole body FDG PET/CT are also performed for select patients. (See 'Imaging' above.)
●Limited role for MRD monitoring – Assessment of the bone marrow for minimal residual disease (MRD) using next-generation flow cytometry or next-generation sequencing is usually reserved for patients on clinical trials. While MRD status is prognostic, data from randomized trials are not available to support using MRD results to guide treatment decisions. (See 'Minimal residual disease assessment' above.)
●Response criteria and survival endpoints – The International Myeloma Working Group response criteria are used to define response to therapy as stringent complete, complete, very good partial, and partial (table 2). (See 'IMWG response categories' above.)
Common definitions of survival endpoints (ie, progression-free survival, time to progression, and duration of response) should be used in reporting clinical research. (See 'Survival end points' above.)
