Role of the Asian Myeloma Network
Dan Navid, JD VP, Global Affairs
International Myeloma Foundation
The IMF in Asia
The IMF is Dedicated to Improve the Quality of Life of Myeloma Patients While Working Towards Prevention and a Cure.
As Part of its Global Effort, IMF Devotes Increased Attention to Myeloma in Asia.
The Centerpiece of IMF's Asian Work is
– The Asian Myeloma Network
Tackle MM in Asia
Epidemiology of MM (Am J Hem 2015)
Clinical Trials
AMN Focus of Work
1. Myeloma Database (led by Korea)
2. Clinical Trials and Treatment Guidelines (led by Singapore)
3. Physician Training (led by China)
4. Diagnosis and Smoldering Myeloma (led by Japan)
AMN Standing Committees
1. Executive Committee
2. International Advisory Committee
3. Program Committee
4. Clinical Trial Committee
5. Virtual Tissue Bank Committee
6. Award Committee
Growth of the AMN
1. Expanding membership
2. Outreach with other regions
3. Refining work arrangements
Annual AMN Summit
9th AMN
October 16-19, 2025
Nagoya, Japan
An Annual Expert Meeting to Review Latest Developments in Myeloma Research and to Determine Work Priorities.
Current AMN Projects
AMN Clinical Trials
Tissue Bank
Virtual Master Class
Objectives
Early access to good treatment
Establish Asian Data
Study combinations that are relevant to Asia
Establish Asia as a partner for Industry in Cooperative group trials
Elevate standing of Asia in myeloma research
Current and Future Trials
in
Current AMN Projects: Virtual Tissue Bank
Current AMN Projects: Master Class
AMN Virtual Masterclass on Novel Immunotherapies – August 4, 2024
• Focused on novel immunotherapies, with consideration of patient selection, early success in this field, problems with toxicity and resistance, and finally future treatment directions
• Chaired by Dr. Wee Joo Chng (National University Hospital—Singapore)
Faculty: Dr. Thomas Martin (UC San Francisco—CA, USA); Dr. Shinsuke Iida (Nagoya City University Hospital—Japan); Dr. Juan Du (Chang Zheng Hospital China); Dr. Dok Hyun (Asan Medical Center S. Korea) and Dr. Chandramouli Nagarajan (Singapore General Hospital— Singapore)
• In person Masterclass planned for October 18, 2024, in Seoul, Korea
Possible New AMN Projects
Preceptorship Program
New Clinical Trials
AMN Executive Committee
Wen-Ming Chen (China)
Jian Hou (China)
James Chim (Hong Kong)
Masahiro Abe (Japan)
Hiroshi Handa (Japan)
Shinsuke Iida (Japan)
Gin Gin Gan (Malaysia)
Sen Mui Tan (Malaysia)
Priscilla B. Caguioa (Philippines)
Rosalio P. Torres (Philippines)
Wee Joo Chng (Singapore)
Chandramouli Nagarajan (Singapore)
Daryl Tan (Singapore)
Jin Seok Kim (South Korea)
Kihyun Kim (South Korea)
Jeffrey Huang (Taiwan)
Teeraya Puavilai (Thailand)
On behalf of the AMN Team,
IMF Executive Vice President of Research & Operations THANK YOU.
Wee Joo Chng
AMN Chairman
Dan Navid
IMF Senior Vice President, Global Affairs
Lisa Paik
Discussion
Global Multiple Myeloma Diagnostic Criteria,
Prognostic Factors, Risk Stratification
Wee Joo Chng, MD
National University Cancer Institute, Singapore, National University Health System
Multiple Myeloma: Diagnosis, prognosis and risk stratification
Prof Chng Wee Joo
Chairman, Asian Myeloma Network
Vice President (Biomedical Research) and Yong Loo Lin Professor in Medical Oncology, NUS
Restricted, Non-Sensitive
Monoclonal protein analysis
Picture courtesy of Drs. R. Kyle and J Katzmann, Mayo Clinic
Monoclonal protein Polyclonal protein “M spike” Polyclonal hump
Restricted, Non-Sensitive
Immunofixation
Restricted, Non-Sensitive
Special Situations
• Light Chain only
• Non-secretory MM
• Serum Free Light Chain assay are useful in monitoring these disease subtypes
• More sensitive than assessment of intact lg
• Normalization of kappa:lambda ratio an important goal
Light Chains – Biology
• Production of free light chains = 500 mg/d
• 40% excess free light chain produced over heavy chain
• κ is usually monomeric, λ usually dimeric
• Twice as many κ than λ producing plasma cells
Serum free light chain analysis. 2nd Ed. A.R. Bradwell
Blood Cancer J 2022
Myeloma Screening Panel
Restricted, Non-Sensitive
What about Serum lgs
• They do not distinguish monoclonal from polyclonal lgs
• However, they may be very useful for lgA MM
Leukemia 2021
Restricted, Non-Sensitive
Causes of monoclonal gammopathy
Restricted, Non-Sensitive
MGUS
Restricted, Non-Sensitive
Asymptomatic / Smouldering Myeloma
Restricted, Non-Sensitive
Symptomatic Myeloma
Restricted, Non-Sensitive
Clinical Features
• Calcium elevation
• Renal disease
• Anemia
• Bone disease
• …and other constitutional
Smith. Br J Haematol. 2005;132:410.
Skeletal Survey
MRI Scan
PET/CT Scan
Restricted, Non-Sensitive
Clinical Application
• ASH Review Article 2013
• Dispenzieri et al. Smoldering Multiple Myeloma requiring treatment: time for a new definition? Blood. 2013 122:4172-4181
Revised IMWG Criteria
Rajkumar. Lancet Oncol 2014; 15: e538-48
Investigations for Diagnosis
• Myeloma screening panel [SPEP, Serum IFE, sFLC]
• M -protein quantification (for response measurement)
• Bone Marrow Aspirate and Trephine
• FBC
• Ca Panel
• Renal Panel
• Skeletal Survey / LD CT Not Bone Scan
• MRI may be needed
Clonal PCs in BM (Flow Cytometry, IHC)
>10% Clonal PCs in BM (Flow Cytometry, IHC) ? MM Defining (FBC, CrCl, Ca, Lytic lesion, sFLC ratio >100)
Amyloidosis, IgM associated neuropathy, Light or heavy chain
Restricted, Non-Sensitive
Prognosis
Revised ISS
Restricted, Non-Sensitive
Not all 17p Del are Bad
Clonal Fraction of 17p Del
Bi-allelic loss of p53
Tharkurta et al. Blood 2019
Walker et al. Leukemia 2018
Outcomes are worse with more poor-risk genetic factors
Double hit MM
Bi-allelic TP53 OR ISS3, +amp (1q)
R2-ISS
Training Set (n=2226)
Validation Set (n=1214)
Summary of the New IMS-IMWG Consensus HRMM
Definition
Criteria for HRMM
Del(17p)a and/or TP53 mutationb
One of these translocations: t(4;14) or t(14;16) or t(14;20), cooccurring with +1q and/or del(1p32)
Monoallelic del(1p32) along with +1q, or biallelic del(1p32)
High β2M (>5.5 mg/dL) with normal creatinine (<1.2 mg/dL)
aCCF ≥20%, by analyses conducted on CD138-positive/purified cells.
bAssessed using an NGS-based method.
+1q, gain (3 copies) or amplification (≥4 copies) of the long arm of chromosome 1; CCF, cancer clonal fraction; HRMM, high-risk multiple myeloma; NGS, next-generation sequencing.
t(x;22) (light chains)
t(8;14)
t(4;14) breakpoint GEP
Chromothripsis
Hyper APOBEC
t(8;14)
t(x;22) (light chains)
GEP
Chromothripsis
t(4;14) breakpoint
Number and size of PET or MRI lesions at diagnosis Extra meduallary disease
IMS 2024
Hyper APOBEC
circulating DNA
circulating plasma cells
plasma cell leukemia
t(x;22) (light chains)
Chromothripsis
t(4;14) breakpoint
Number and size of PET or MRI lesions at diagnosis Extra meduallary disease
t(8;14)
t(x;22) (light chains)
Chromothripsis
t(4;14) breakpoint
IMS
Number and size of PET or MRI lesions at diagnosis Extra meduallary disease
Functional Risk Dynamic response to therapy - MRD
Hyper APOBEC
Microenvironment circulating DNA
Factors
Risk Stratification
1) Revised ISS 1
2) No CA
3) <55 years
1) IMS-IMWG HR
2) Functional HR
Median OS >10 years 8 years 2 years
Therapeutic
Questions ? Need CR or MRD? Need maintenance Aim to increase cure fraction Aim for MRDAim for maintenance
Need to test different strategy High risk procedure e.g. AlloSCT New therapeutics
These are patients that will benefit most from modern drugs and treatment paradigm and the potential group that we can aim for cure
Thank you.
Discussion
Break
Treatment option in Asia
Newly Diagnosed Transplanteligible Myeloma Patients
Hiroshi Handa Department of Hematology
Gunma University Graduate School of Medicine Japan
• Research Support
• Employee NA
• Consultant NA
• Major Stockholder NA
• Speakers Bureau NA
• Honoraria Janssen, Takeda, BMS, Ono
• Scientific Advisory Board Pfizer, Abbvie, Janssen, Takeda
Myeloma survival continues to improve
(Mortality trends in multiple myeloma after the introduction of novel therapies in the United States)
Innovation of Treatment is contributing to the improvement
Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms
in the novel drug era (2016-2021)
Shibayama H, et al. Int J Hematol. 119:707-721.
Autologous stem cell transplantation in Asian countries
Shimazu Y, et al. Cancer Sci. 112; 5034-5045. 2021
Huang TC, et al. J Formos Med Assoc. 118: 471-480 2019
Cheong CS, et al. Asian Pac J Cancer Prev;25(2):595-601. 2024
Kang KW, et al. (KMMWP) BMC Cancer.;25:204. 2025
Treatment benefit of upfront ASCT for newly diagnosed multiple myeloma: a systematic review and meta-analysis
Lin CM, et al. BMC Cancer 23: 446 (2023)
RVD+HDT+ASCT vs RVD alone Phase III DETERMINATION TRIAL
RVD+ASCT was associated with longer PFS than RVD alone, but no OS benefit was observed
So Question is,
• ASCT has long been considered to be the standard care.
• Do we need upfront ASCT for all NDMM-TE patients?
• If upfront ASCT did not show any OS difference, would deferring ASCT be a reasonable strategy?
• But some patients seem to need ASCT for longer OS How can we distinguish and construct effective strategy?
Depth of Response is important for OS
Ozaki et al. Japanese Society of Myeloma retrospective analysis
Measurable Residual Disease by Next-Generation Flow Cytometry
in Multiple Myeloma
PETHEMA/GEM2012MENOS65 clinical trial
MRD negativity using NGS is major prognostic factor (IFM 2009 trial)
MRD negativity appears to be a stronger predictor of favorable outcome in both PFS and OS than ISS stage, cytogenetics
• MRD negativity is important and could be a surrogate endpoint of PFS/OS in the novel agent era.
• Could we construct MRD guided strategy for NDMM-TE patients?
• Before proceeding, let me talk about stronger induction/ consolidation/maintenance therapeutic regimen namely quadruplet regimen (anti-CD38 antibody+ PI+ IMiDs+ Dex), potentially have power deepening responses.
Clinical Trials with Quad Therapy including anti-CD38 antibody
Daratumumab + Bortezomib + Thalidomide +
(D-VTD) vs VTD CASIOPEIA study
Moreau P. et al. Lancet. 394: 29-38. 2019
Daratumumab + RVd for NDMM GRIFFIN
Voorhees PM, et al. Blood Adv. 5(4):1092-1096. 2021
PFS of Daratumumab + RVd for TE-NDMM (PERSEUS)
Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd
Byun JM, et al. Blood
GMMG-HD7: Isatuximab + VRd vs VRd
GMMG-HD7: MRD
negativity and response rate at end of induction
Main results of anti-CD38 monoclonal antibodies into ASCT program in newly diagnosed MM patients.
CASSIOPEIA [23,24] 3
GRIFFIN [25,26] 2
VTd vs. D-VTd induction (4 cycles) and consolidation (2 cycles), with D maintenance or observation Day 100 after ASCT
D-VRd induction (4 cycles) and consolidation (2 cycles) plus DR maintenance or VRd induction (4 cycles) and consolidation (2 cycles) plus R maintenance
(64% vs. 44%)
PERSEUS [27] 3
D-VRd induction (4 cycles) and consolidation (2 cycles) plus DR maintenance c or VRd induction (4 cycles) and consolidation (2 cycles) plus R maintenance
MASTER [28] 2 D-KRd induction (4 cycles) and consolidation (2 cycles), with R maintenance or observation e
GMMG-HD7 [34] 3
GMMG-CONCEPT [35] 2
Isa-VRd vs. VRd induction (3 cycles) with maintenance with Isa-R or R After induction therapy (50% vs. 36%) Ongoing g
Isa-KRd induction (6 cycles) and consolidation (4 cycles) with Isa-KR maintenance h
(68%) i NR
Measurable
Residual Disease-Guided Therapy in Newly Diagnosed Myeloma (IFM2020-02 MIDAS study)
Among patients who were MRD-negative at 10-5 sensitivity after induction, the percentage with a premaintenance
MRD-negative status at 10-6 sensitivity was not significantly higher with ASCT than with Isa-KRd.
→If the patients get into MRD-negative by Isa-KRd, ASCT could not win Isa-KRd. Perrot A. et al.
Indirect comparisons of MRD-negativity rates after induction in ITT populations of studies focused on patients with transplant-eligible newly diagnosed MM
A quick break story
• Midas was a king of Phrygia, with whom many myths became associated.
• The most famous King Midas is popularly remembered in Greek mythology for his ability to turn everything he touched into pure gold and this came to be called the golden touch, or the Midas touch. [1]
• The Tragedy: Midas' daughter turns to a golden statue when he touches her
• Will the treatment scheme like MIDAS become the golden standard?
MRD oriented treatment for transplant eligible NDMM MASTER Trial
MRD kinetics differ according to cytogenetic risk: MASTER Trial
Around 40% achieved 10-5 MRD negative post induction, 60% post ASCT, 80% post consolidation.
And the almost same response was observed in the patients with high-risk cytogenetic abnormality (HRCA).
Caution !!
Even though 2+High risk cytogenetic abnormality (Ultra high risk) patients had deep, but the percentage of the patients with relapse after discontinuation was higher.
Costa LJ, et al. J Clin Oncol. 40: 2901-2912. 2022
Cytogenetic risk stratification combined with minimal residual disease status influences the therapeutic outcome
and prognosis of multiple myelomas
The median PFS (C) and OS (D) in MM patients divided by the cytogenetic risk stratification combined with the MRD status.
Mao J et al. Sci Rep. 2025 Apr 12;15(1):12545.
Next question
• How old should we or can we treat with ASCT?
• MM is predominantly a disease of older adults, with a median age at diagnosis of 69 years and over one-third of new cases occurring in patients aged 65 to 74 years.
How old is ASCT effective for ? ASCT for elderly patients (age>65)
Age no bar: A CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma
MM is predominantly a disease of older adults, with a median age at diagnosis of 69 years and over one-third of new cases occurring in patients aged 65 to 74 years.
Among patients who received Mel at a dose of 200 mg/m2, there was no difference in OS noted by age group
Mel at a dose of 140 mg/m2 was associated with a worse NRM. both PFS and OS were worse among the patients aged ≥70 years who were treated with Mel at a dose of 140 mg/m2 Munshi PN et.al, Cancer. 127(20):3904. 2021
Autologous stem cell transplantation is safe and effective for fit, older myeloma patients: exploratory results from the Myeloma XI trial
Pawlyn C. et al. Haematologica. 107: 231-242. 2022
Autologous stem cell transplantation is safe and effective for fit, older myeloma patients: exploratory results from the Myeloma XI trial
Pawlyn C. et al. Haematologica. 107: 231-242. 2022
Daratumumab for newly diagnosed multiple myeloma: Pooled analysis of patients aged ≥65
years from GRIFFIN and
PERSEUS
MM is predominantly a disease of older adults, with a median age at diagnosis of 69 years and over one-third of new cases occurring in patients aged 65 to 74 years.
A trend in improved PFS was seen among patients aged ≥65 years favoring D-VRd
These data support use of D-VRd followed by D-R maintenance as standard of care for all transplant-eligible patients with NDMM, regardless of age up to 70 years.
Meaning of continuous/maintenance therapy
VRd followed by autologous stem cell transplant
Maintenance is important especially for High-risk cytogenetics
Sidiqi MH et al. Blood Cancer J. 2018;8(11):106.
Goldschmidt H et al, Leukemia.34: 3019-3027. 2020
Maintenance with daratumumab or observation following treatment with VTD with or without daratumumab and ASCT
in
patients
with NDMM (CASSIOPEIA)
Moreau P et al. Lancet Oncol. 25:1003-1014. 2024
Kang KW, et al. (KMMWP) BMC Cancer.;25:204.
Lenalidomide remains the maintenance therapy of choice for patients with NDMM
Lenalidomide and daratumumab but not ixazomib were associated with improved PFS compared with placebo in patients with TEMM None of the agents showed an OS benefit, and PFS benefits were not seen in patients with high-risk cytogenetics.
Lai E, et al. Blood Neoplasia (2024) 1 (4): 100042.
Stem Cell Mobilization and Harvesting
• A minimum of 2 × 106/kg CD34+ cells is required to perform ASCT, while the ideal target for 1 ASCT is >3 × 106/kg CD34+ cells, and that for 2 ASCT is >6 × 106/kg CD34+ cells.
• Stem cell mobilization can be performed with granulocyte colonystimulating factor (G-CSF), preceded or not by chemotherapy with Cyclophosphamide (Cy) at a variable dose of 1.5–4 g/m2.
• Plerixafor (scissor enzyme selective and reversible antagonist of CXCR4) has been approved, which is particularly effective in reducing the failure rate.
Stem Cell Mobilization and Harvesting
• After plerixafor approval, the chemotherapy-free protocol has been adopted by many centers because of the less adverse event rates, such as neutropenia or infections.
• Recent data seem to indicate that the introduction of anti-CD38 monoclonal antibodies in the induction therapy of NDMM is associated with a lower capacity to mobilize and collect HSC.
HDT-ASCT is a potentially toxic therapy
• Treatment related toxicity (TRM) <5%, <1% in expert centers
• Acute HDM-ASCT toxicity
Prolonged bone marrow suppression, infection, VOD (0.4%), Interstitial
Pneumonitis (0.5-8%), autologous GVHD (18%), graft failure (0.6%) (Fermand JP, Blood 92: 3131;1998)
• Decline of QoL
• Increased risk of secondary malignancies
AML/MDS risk is 11.5-fold higher in MM compared to general population.
AML/MDS risk is 50-fold and 100-fold higher respectively among patients treated with HDT-ASCT compared to the general population
The risk is approximately 10-fold higher than non-transplant patients.
Recent genomic study revealed that new mutational signature in previously exposed to high dose melphalan.
Relative risks of AML and MDS after autologous stem-cell transplant (CIBMTR data) or diagnoses (SEER data) for patients with MM
Patients receiving autologous transplant are at up to a 50-fold increased risk of developing AML compared to 10-fold and up to 100-fold risk of developing MDS compared to fivefold.
High dose melphalan induces mutation
EH, et al. Nat Commun. 11(1):1917. 2020
FZ et al. Mod Pathol. 36(6):100166.2023
Rustad
Jelloul
T cell-redirecting therapy in the front-line setting in transplant-eligible MM patients
KarMMa-4 NCT04196491 1
NDMM, TE bb2121 autologous CAR T cells + R as maintenance
NCT01352286
1/2
, TE b anti-CD3/anti-CD28-costimulated autologous T cells after ASCT c
Teclistamab + DRd ± V as induction and Teclistamab + DR as maintenance
Teclistamab + R vs Teclistamab vs R as maintenance after ASCT
+ Talquetamab + D
Positioning of ASCT
1. Recent advancement of induction treatment i.e. quadruplet regimen may change the treatment scheme in near future.
2. Including more potent drugs or antibody such as BCMA-bispecific antibody for the primary therapy will be likely pushed further in that direction
3. Using BCMA CAR-T instead of ASCT
4. But these T cell redirecting therapies are expensive, thus, despite its toxicity and limited ability to prolong OS, ASCT remains the standard treatment for NDMM-TE patients.
5. MRD driven and deferring ASCT may work.
Thank you !
Discussion
Close of Morning Session & Announcements
Dan Navid, JD VP, Global Affairs
International Myeloma Foundation
LUNCH
