Multiple%20myeloma Management

Management

Response Assessment

Assessment of clinical response is recommended after every treatment cycle

International Myeloma Working Group (IMWG) Criteria for Response Assessment

Category	Criteria
IMWG Minimal Residual Disease (MRD) Criteria
Sustained MRD-negative	No MRD in the marrow as defined by next-generation flow (NGF), next-generation sequencing (NGS), or both, and in imaging*, within a minimum span of 1 year apart. Specific duration of negativity to be based on subsequent evaluations
Flow MRD-negative	Phenotypically aberrant clonal plasma cells by NGF absent in bone marrow aspirate using the EuroFlow standard operating procedure for MRD detection in multiple myeloma with sensitivity of ≥1 in 10⁵ nucleated cells
Sequencing MRD-negative	Clonal plasma cells by NGS absent in bone marrow aspirate; clone present defined as <2 identical sequencing reads obtained after DNA sequencing of bone marrow aspirates by a validated equivalent methods with sensitivity of ≥1 in 10⁵ nucleated cells
Imaging plus MRD-negative	MRD-negative as defined by NGF or NGS, plus complete disappearance, decreased to less mediastinal blood pool standardized uptake values (SUV), or decreased to less than that of the surrounding normal tissue, of tracer in previous areas identified with increased tracer uptake at baseline or preceding PET/CT
Standard IMWG Response Criteria
Complete response	Negative serum and urine immunofixation without any soft tissue plasmacytomas and <5% plasma cells in bone marrow aspirates
Stringent complete response	Complete response plus normal FLC ratio^◊ and negative clonal cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 for κ or ≥1:2 for λ patients after counting ≥100 plasma cells)
Very good partial response	Serum and urine M-protein detectable by immunofixation but not on serum protein electrophoresis (SPEP), or ≥90% reduction in serum M-protein with urine M-protein <100 mg/24 hours
Partial response	Serum M-protein reduced by ≥50%, plus ≥90% reduction of 24-hour urinary M-protein, or <200 mg/24 hours urinary M-protein Or ≥50% reduction in plasma cells (in place of M-protein) if with baseline bone marrow plasma cell percentage of ≥30% plus ≥50% reduction in size of soft tissue plasmacytomas if obtained at baseline
Minimal response	≥25% but ≤49% reduction in serum M-protein and 50-89% reduced 24-hour urine M-protein or 25-49% reduction in size of soft tissue plasmacytomas if obtained at baseline
Stable disease	Does not meet the criteria for complete response, very good partial response, partial response, minimal response, or progressive disease Not recommended to be used as an indicator of response
Progressive disease	25% increase from lowest confirmed response value in ≥1 of the following: Serum M-protein (absolute increase ≥0.5 g/dL) Serum M-protein increase ≥1 g/dL, if lowest M component was ≥5 g/dL Urine M-protein (absolute increase ≥200 mg/24 hours) The difference between involved and uninvolved FLC levels in patients without measurable serum or urine M-protein levels (absolute increase >10 mg/dL) Bone marrow plasma-cell percentage irrespective of baseline status in patients with no measurable serum M-protein, urine M-protein, and involved FLC levels (absolute increase must be ≥10%) Presence of new lesion(s), ≥50% increase from nadir in SPD† of >1 lesion, or ≥50% increase in longest diameter of previous lesion >1 cm in short axis ≥50% increase in circulating plasma cells (≥200 cells/μL) if other tests are unavailable
Clinical relapse	≥1 of the following: Presence of indicators for increasing disease and/or end-organ dysfunction (CRAB features) related to underlying clonal plasma-cell proliferative disorder Presence of new soft tissue plasmacytomas or bone lesions (except osteoporotic fractures) 50% or ≥1 cm increase in size of existing plasmacytomas or bone lesions serially measured by the SPD^† of measurable lesions Hypercalcemia (>11 mg/dL) Hemoglobin level decreased by ≥2 g/dL unrelated to any therapeutic regimen or other non-myeloma-related conditions An increase in serum creatinine by ≥2 mg/dL during therapy initiation and attributable to myeloma Hyperviscosity related to serum paraprotein
Relapse from complete response^#	≥1 of the following: Reappearance of serum or urine M-protein by immunofixation or electrophoresis Development of ≥5% plasma cells in bone marrow Appearance of any other signs of progression (eg new plasmacytoma, lytic bone lesion, hypercalcemia)
Relapse from MRD-negative^#	≥1 of the following: Presence of clonal plasma cell on NGF/NGS, positive for recurrence in imaging studies (loss of MRD-negative status) Reappearance of serum or urine M-protein by immunofixation or electrophoresis Development of ≥5% plasma cells in bone marrow Appearance of any other signs of progression (eg new plasmacytoma, lytic bone lesion, hypercalcemia)

Adapted from: International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. 2016.

*Negative imaging results defined as complete disappearance, decreased to less mediastinal blood pool SUV, or decreased to less than that of the surrounding normal tissue, of tracer in previous areas identified with increased tracer uptake at baseline or preceding PET/CT

◊Validated by Freelite test

†Sum of the products of the maximal perpendicular diameters of measured lesions
^#If endpoint is disease-free survival

Follow Up

Treatment response should be evaluated after every therapy cycle (see Response Assessment)
Recommended laboratory tests during follow-up or surveillance include CBC with differential and platelet count, serum creatinine level, calcium level, serum and urine M-protein level, and immunoglobulin studies should be obtained
May consider the following tests as clinically indicated:
- Serum quantitative immunoglobulins, serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE)
- 24-hour urine for total protein, urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) at baseline, as clinically indicated in patients post-primary treatment, as needed post-HCT, or if with significant change in FLC levels
- Serum FLC assay: Should be obtained every 2-3 months or as clinically indicated
- Imaging modalities (eg whole body MRI without contrast, low-dose CT scan, WBLD-CT, whole body FDG PET/CT): To be done annually after primary treatment or as clinically indicated; test done at diagnosis is preferred
  - Skeletal survey may be done in certain circumstances
- Bone marrow aspirate and biopsy with multiparameter flow cytometry as clinically indicated after primary treatment or as needed after HCT
- Minimal residue disease assessment
Patients receiving Carfilzomib should be closely monitored for any cardiac or lung toxicities
Occurrence of new bone lesions should be monitored using patient history and imaging modalities (eg skeletal radiography, MRI, WBLD-CT, PET-CT)
Follow-up bone imaging may be considered if disease progression is suspected

Product Highlight - Cabometyx

29 Sep 2021

Cabozantinib 60 mg, 40 mg and 20 mg tab

Immunotherapy sparks hope for paediatric ALL

Audrey Abella, 14 Oct 2020

Despite a 90-percent cure rate after first treatment for children with acute lymphoblastic leukaemia (ALL), approximately 10–15 percent of patients with paediatric ALL will experience relapse. [Expert Rev Anticancer Ther 2017;17:725-736] A recent webinar on the current landscape of ALL highlighted the potential of immunotherapy for paediatric patients with relapsed or refractory ALL, thus providing hope for this high-risk patient group.

SARS-CoV-2 Variants: Everything you need to know

01 Feb 2023

The COVID-19 pandemic continues to evolve with the emergence of new SARS-CoV-2 variants. The variants of concern have the potential to impact the transmissibility, virulence, and clinical presentation of the disease, affecting the epidemiology, public health measures, and diagnostic and therapeutic options. Mutations in the spike protein of the virus have increased its ability to infect humans and evade neutralization by natural or immunisation-induced antibodies. The highly mutated Omicron variant of SARS-CoV-2 has multiple sublineages with varying transmissibility and immune evasion potential. Pre-exposure prophylaxis plays a crucial role in protecting the immunocompromised populations against severe disease; however, the rapidly changing landscape of the variants poses a major challenge to the current and future effectiveness of pre-exposure prophylactic monoclonal antibodies.