Day Two Sessions: ASCO 2016 - Multiple Myeloma Research Foundation

Day Two Sessions: ASCO 2016

The MMRF team is spending nearly a week at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting and we are pleased to share with you some key highlights from the multiple myeloma (MM) data presented. The oral session this morning attracted a large crowd of attendees, so there was much anticipation for the data!

Updated Diagnostic Criteria and Staging System for Multiple Myeloma

Author: S. Vincent Rajkumar, MD Division of Hematology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905; email: rajkumar.vincent@mayo.edu.

Overview
There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several new active drugs. These advances have necessitated a revision of the disease definition and staging of MM. Until recently, MM was defined by the presence of end-organ damage, specifically hypercalcemia, renal failure, anemia, and bone lesions (CRAB features) that can be attributed to the clonal process. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria for MM to add three specific biomarkers that can be used to diagnose the disease in patients who did not have CRAB features: clonal bone marrow plasma cells greater than or equal to 60%, serum free light chain (FLC) ratio greater than or equal to 100 provided involved FLC level is 100 mg/L or higher, or more than one focal lesion on MRI. In addition, the definition was revised to allow CT and PET-CT to diagnose MM bone disease. These changes enable early diagnosis and allow the initiation of effective therapy to prevent the development of end-organ damage for patients who are at the highest risk. A new staging system has been developed that incorporates high-risk cytogenetic abnormalities in addition to standard laboratory markers of prognosis.

Key Points

  • The diagnostic criteria for multiple myeloma and related disorders have been updated by the International Myeloma Working Group.
  • Patients with 60% or more clonal plasma cell involvement of the marrow, serum free light chain ratio of 100 or higher (provided involved free light chain level ≥ 100 mg/L), and/or greater than one focal lesion on MRI are defined as MM even in the absence of end-organ damage.
  • Low-dose whole-body CT, MRI, and FDG-PET and FDG-PET with PET-CT are more sensitive in detecting myeloma and must be considered in diagnosis and monitoring.
  • In terms of renal involvement, only light chain cast nephropathy is considered a myeloma-defining event.
  • The Revised International Staging System has been developed for myeloma that incorporates high-risk cytogenetic abnormalities.

The Role of Imaging in the Treatment of Patients With Multiple Myeloma in 2016

Author: Evangelos Terpos, MD, PhD, Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra General Hospital, 80 Vas. Sofias Ave., 11528, Athens, Greece; email: eterpos@med.uoa.gr.

Overview
The novel criteria for the diagnosis of symptomatic multiple myeloma have revealed the value of modern imaging for the management of patients with myeloma. Whole-body low-dose CT (LDCT) has increased sensitivity over conventional radiography for the detection of osteolytic lesions, and several myeloma organizations and institutions have suggested that whole-body LDCT should replace conventional radiography for the work-up of patients with myeloma. MRI is the best imaging method for the depiction of marrow infiltration by myeloma cells. Whole-body MRI (or at least MRI of the spine and pelvis if whole-body MRI is not available) should be performed for all patients with smoldering multiple myeloma with no lytic lesions to look for occult disease, which may justify treatment. In addition, MRI accurately illustrates the presence of plasmacytomas, spinal cord, and/or nerve compression for surgical intervention or radiation therapy; it is also recommended for the work-up of solitary bone plasmacytoma, and it may distinguish malignant from benign fractures (which is very important in cases of patients in biochemical remission with no other signs of progression). Diffusion weighted imaging (DWI) seems to improve MRI diagnosis in patients with myeloma. PET/CT is a functional imaging technique, more sensitive than conventional radiography for the detection of lytic lesions, which probably allows better definition of complete response and minimal residual disease compared with all other imaging methods. PET/CT has shown the best results in the follow-up of patients with myeloma and has an independent prognostic value both at diagnosis and following treatment. PET/CT can also be used for the work-up of solitary bone plasmacytoma and nonsecretory myeloma.

Key Points

  • Whole-body LDCT is superior to conventional radiography for the detection of osteolytic lesions, and it is suggested to replace it in the work-up of patients with myeloma.
  • MRI is the best imaging method for the depiction of marrow infiltration by myeloma cells.
  • Whole-body MRI (or at least MRI of the spine and pelvis if whole-body MRI is not available) should be performed for all patients with smoldering multiple myeloma with no lytic lesions to look for occult disease, which may justify treatment.
  • PET/CT allows better definition of complete response and minimal residual disease.
  • PET/CT has an independent prognostic value both at diagnosis and after treatment.


Future Directions in the Evaluation and Treatment of Precursor Plasma Cell Disorders

Authors: Irene M. Ghobrial, MD, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02115; email: Irene_ghobrial@dfci.harvard.edu.
Overview

Multiple myeloma (MM) is an incurable disease that progresses from a premalignant stage termed monoclonal gammopathy of undetermined significance (MGUS) and an intermediate stage of smoldering multiple myeloma (SMM). Recent major advances in therapy with more effective and less toxic treatments have brought reconsideration of early therapeutic intervention in management of SMM, with the goal of reducing progression of the disease before the occurrence of end-organ damage to MM and improving survival. Key to this effort is accurate identification of patients at high risk of progression who would truly benefit from early intervention. In this review, we discuss the current definitions, risk factors, risk stratification, prognosis, and management of MGUS and SMM, as well as new emerging therapeutic options under active investigation.

Key Points

  • Multiple myeloma is always preceded by precursor conditions including MGUS and smoldering myeloma.
  • The rate of progression of MGUS is at 1% per year, but the rate of progression of SMM is 10% per year, with a high rate of progression of 50% at 2 years for those with high-risk features.
  • Patients with high-risk SMM should be offered clinical trials to prevent progression or carefully observed to avoid end-organ damage.
  • Patients with MGUS and SMM have different risk stratifications and rates of progression.
  • Some patients may benefit from early therapeutic interventions, specifically in high-risk SMM.

Posted: June 04, 2016

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