2025 AMN Master Class Slides Sunday

Check out by 12 Lunch is provided

Clinical Cases Presented by Attendees Moderated by Wee Joo Chng, MD Panelists: James CS Chim, MD, PhD Hiroshi Handa, MD Chandramouli Nagarajan, MD, & Daryl Tan, MD

#1: Dr. Chee Chiat Liong

AMN Case presentation: Liong Chee Chiat, UMMC Malaysia 60-year-old man -

Presented with backache for 2 months, worsening steadily Partially relieved by analgesia Feeling more tired than usual

Examination: mild pallor, no other significant abnormalities Investigations: Hb 10.4 g/dL, WBC 4.2 x10^9/L, Platelets 151 x10^9/L Creatinine 72 umol/L, Corrected calcium 2.44 mmol/L, Albumin 38 g/L, Globulin 53 g/L

Work-up MRI spine: multiple compression fracture from T5 to L2 CT thorax-abd-pelvic: diffuse multiple ill defined lytic lesions at thoracic, lumbar and sacral spines Bone marrow examination: 93% plasma cells positive for CD138, CD56, and cytoplasmic lambda Karyotype: 46, XY; FISH: no evidence of fusion gene rearrangement or gene deletion Diagnosis: Multiple myeloma IgG Lambda, ISS I

Treatment

Newly diagnos ed myeloma

Maintenance

2nd relaps e

M protein 22 g/ L, s tarted on Bortezomib-Cyclo-Dexa 1# then Borte-Lenalidomide-Dexa (BRD) 3#

M protein not detected, s tarted on Lenalidomide maintenance

CR after 8# DVd, on monthly Dara but developed cytopaenias with M protein 2.4, repeat marrow 39% plas ma cells

Aug 2019

Feb 2019

Nov 2023 Feb 2020

April 2025 Feb 2025

Autologous HSCT

Dis eas e relaps ed

CAR-T therapy

M protein <1, ASCT performed then cons olidated with BRD 2# , complicated with PCP + drug allergic reaction

M protein 5, developed pancytopaenia s ince J une 2023 ? MDS, repeat marrow noted 85% plas ma cells with TP53 detected, s tarted on Daratumumab-Borte-Dex (DVd)

Ineligible for Teclis tas tam ab trial, patient went for CAR-T therapy

Latest development Now 67-year-old, clinically well, ECOG 1 M protein < 1 g/L Hb 7.3 g/dL, WBC 3.1 x10^9/L, Platelets 27 x10^9/L Kappa free light chain 12.1 mg/L, Lamda 29.4 mg/L, ratio 0.41 (0.31-1.56) Repeat marrow: hypercellular marrow with erythroid hyperplasia, no increased in plasma cells PETCT: interval reduction in metabolic activity at diffusely intense FDG uptake involving the axial and appendicular bones - good partial response

Questions Any role of 2nd autologous haematopoeitic stem cells transplant (stem cells harvested) in this patient (and the timing)?

-

How about other myeloma patients?

Is there any ‘maintenance/ consolidation’ therapy to be given post CAR-T? What would be recommended next line of therapy in 3rd relapse?

-

Pomalidomide-based Carfilzomab-based Selinexor Teclistamab (not readily accessible outside trial) Chemotherapy: DT-PACE/ Bendamustine??

Venetoclax???

Melphalan-Pred-Thalidomide

#1: Dr. #2: Dr. Thi Nhung NguyenChiat Liong Vietnam

AMN 2025

Case presentation MM relapse after ASCT Nguyen Thi Nhung Stem cell transplantation department, National Institute of Hematology and Blood Transfusion, Viet Nam

At diagnosis • • • • •

Male, 58 y/o Date of hospital admission: 2020 April Past Medical History: Previously healthy Reason for Admission: Fatigue and bilateral leg edema.

History of Present Illness: – 1 month prior to admission, the patient experienced progressive fatigue and bilateral leg edema and aching pain in the lumbar spine.

– Initial workup at a provincial hospital revealed anemia, renal dysfunction, and hypercalcemia. Multiple myeloma was suspected, and the patient was referred to the NIHBT in April 2020 for further evaluation and management.

At diagnosis: Laboratory and diagnostic investigations Hematology & Biochemistry: - Hemoglobin: 70 g/L - Urea: 8.2 mmol/L - Creatinine: 211 µmol/L, CrCl 32 mL/min/1.73 m² - Total protein: 120 g/L (Albumin: 23 g/L) - Beta-2 microglobulin: 12 mg/L - Calcium: 2.8 mmol/L - LDH: 570 U/L

Immunoglobulins & Light Chains: - IgG: 8632 mg/L - IgA: 21.9 mg/L - IgM: 16 mg/L - Kappa light chains: 128 mg/L - Lambda light chains: 11.8 mg/L

• Serum Protein Electrophoresis and Immunofixation: Monoclonal peak in beta-globulin region, consistent with IgG-Kappa monoclonal protein.

• Bone Marrow Biopsy: >60% plasma cell infiltration • MRI (Spine): Vertebral compression fractures at L1–L3, multiple lytic lesions in vertebral bodies, lumbar disc herniation.

• FISH Analysis: Negative for t(4;14), t(14;16), t(14;20), dups 1q, del13p, del17q

58 y/o, male, IgG-K type, R-ISS: III, Renal failure, Eligible for ASCT Regimen

VCd x 2

DVTd x 3

Cy 4g/m2

Mel 200mg/m2

SC dose 4.2 x 10^6 Symptoms At

Fatigue, Edema

diagnosis

Bone pain

Hb (g/L) 70

Improvement VCd x 2

No edema

105

No bone pain DVTd x 3

Normal

ASCT

Cons VRd x 2

(2021 Feb)

Maintenance R

1.5 years after ASCT

Maintenance R

4 years

Relapse

after ASCT

Bone pain

130

Biochemistry Cre 211, B2M 12 IgG 8632, K 128 Cre 109, B2M 5.2

Immunofixation IgG-K

IgG-K

IgG 1014, K 15

Plasmo 60% FISH negative

Minimal response

IgG-K

Plasmo < 5%

VGPR

Normal

Normal

trace IgG-K

Plasmo < 5%

Normal

Normal

No peak

Plasmo < 5%

115

Cre 105, B2M 3.8 IgG 3025, K 68

Response

Plasmo 50%

IgG 5200, K 68 B2M 2.8

Bone Marrow

IgG-K

Plasmo 30% FISH negative

CR

Treatment???

Clinical Question 1. Is the timing of the transplant appropriate? Should we treat more aggressively to achieve CR before transplantation?

2. We had some cases of failed mobilization using Cyclophosphamide (2-4g/m2)? What should we do? (Plerixafor is unavailable) 3. When should we start treatment for relapse MM (asymptomatic biochemical or symptomatic relapse)?

4. What is the suitable treatment for this patient? 

Retreat and maintain Daratumumab



Use Ixazomib (IRd)



The second transplant

Carfilzomib, Bispecific, CAR T are unavailable

#1: Dr. #3 Dr. Yi-Wei Lee Taiwan

NTUH

Multiple Myeloma Case Yi-Wei, Lee National Taiwan University Hospital

64 y/o

# Resolved HBV infection, under Vemlidy # Hypertension # Dyslipidemia

2024/07 Smoldering MM 2024/10 Smoldering MM

2024/12 MM

2023/05

2024/01 Smoldering MM

Foamy urine=> IgA/kappa monoclonal gammopathy (IFE)

BM study: 18% cPC M protein: 2.3g/dl

BM study: 33% cPC M protein: 2.9g/dl

Light chain ratio: 74.2 M protein: 3.3g/dl

Light chain ratio: 106.2 (SLiM criteria)

X CRAB or osteolytic lesion O FISH: 1q amplification, t(4;14)/IGH::FGFR3 O High risk feature*1 (2/20/20)

X CRAB or osteolytic lesion O Lower back pain BW loss O High risk feature*2

O High risk feature*3

Hb: 13 > 10.6 g/dl Cr: 0.7 > 1.6 mg/dl Ca: 2.15 mmol/L LDH: 156 mg/dl Albumin: 3.4 g/dl Beta-2 Microglobulin: 3.2 mg/dl

ISS stage II, R-ISS stage II, R2 ISS stage III

Multiple myeloma, IgA/kappa type, t(4;14), 1q amplification ISS stage II, R-ISS stage II, R2 ISS stage III

Dara-VTD 137.2

2023/05

2024

2025

Multiple myeloma, IgA/kappa type, t(4;14), 1q amplification ISS stage II, R-ISS stage II, R2 ISS stage III

331.2

Dara-VTD DECP 137.2

2023/05

2024

2025

IFE negative Light chain escape

Clinical Questions in This Patient 1.

Should cytogenetic high-risk smoldering multiple myeloma be treated actively?

2.

What factors predict failure of daratumumab-based therapy despite an initial response?

3.

In transplant-eligible patients who relapse prior to autologous stem cell transplantation, is auto-HSCT still a feasible treatment option? or novel agents will be better options?

#1: Dr. #4 Dr. Young Hoon Park Ewha University

AMN Master Class

Case presentation Young Hoon Park, MD Division of Hematology, Department of Internal Medicine Ewha Womans University Medical Center, Mokdong Hospital, Republic of Korea

Female/32 years old  Incidentally detected anemia and monoclonal protein on health screening (November 2023)  No comorbidities and no specific symptoms  No family history of malignancies  Married woman (6 months ago) without kids == Lab ==  CBC: 9330-10.8-278K, ANC 5640  Total Ca: 8.7 (ref. 8.6-10.2 mg/dL), Creatinine 0.76 (0.63-1.01 mg/dL)  Total protein 13.0 (6.4-8.3 g/dL), Albumin 3.4 (3.5-5.2 g/dL)  Uric acid 6.4 (2.4-5.7 mg/dL)  Lactate dehydrogenase 302 (135-214 IU/L)  IgG/A/M 7452 (700-1600 mg/dL)/ 61.6 (70-400 mg/dL)/ 57 (40-230 mg/dL)  Serum EP/IFE: 6.66 g/dL, IgG-kappa  24hr urine EP/IFE: 30.5 mg/day, IgG-kappa

Female/32 years old  Serum free light chain assay: kappa/lambda 376.71/8.04  B2-macroglobulin 2.89 mg/L  Bone marrow: plasma cell 32.2%  NGS: BRAF (Tier1)  FISH: t(4;14)  MRI & PET: Diffusely and focally hypermetabolic bone lesions in left 5th rib, both humerus, both scapulae, spines, both pelvic bones, both proximal fumora

Final diagnosis #. MM, IgG-kappa, CRAB(-/-/+/+), ISS 2, R-ISS 3, transplant-eligible

Progression Response

D-VTD#1 (Nov 2022)

D-VTD#2 (Dec 2022)

G-CSF mobilization

Autologous stem cell transplantation (Mar 2023)

Response

sCR

sCR

CR

CR

PR

D-VTD#3 (Jan 2023)

D-VTD#4 (Feb 2023)

Lenalidomide maintenance (Aug 2024) sCR on D+100

sCR

sCR

Progression Plan for PR pregnancy

Lenalidomide maintenance sCR

Stop (June 2025) sCR

Follow-up

Questions?  Q1: For young myeloma patients with high-risk cytogenetics, what do you consider the optimal initial treatment strategy? Should our approach differ significantly from that for older, high-risk patients?

 Q2: How do you find the optimal balance between 'treatment intensity' and 'preserving long-term QoL' in these young patients? Specifically, what are your perspectives on the duration of maintenance therapy or strategies for managing treatment-related toxicities?  Q3: Considering the expected long-term survival in young myeloma patients, beyond managing disease recurrence, what are the most crucial long-term complications that we, as clinicians, should focus on to enhance their quality of life?

#1: Dr. #5: Dr. Natasha Fay Anthony Navigating Upfront Choices in Young Standard-Risk Myeloma Presenter: Dr Natasha Fay Anthony (Singapore Integrated Programme for Haematology, Senior Resident)

AMN Masterclass 27/7/25

Case Presentation Navigating Upfront Choices in Young Standard-Risk Myeloma Presenter: Dr Natasha Fay Anthony (Singapore Integrated Programme for Haematology, Senior Resident)

Case Presentation

• 32 year old male, ECOG 0 • Presented with back pain and general weakness; noted bone lytic lesions on spine imaging and underwent vertebroplasty + bone biopsy in 2020 – diagnosed myeloma ‘ • Standard risk with t(11;14) • Started Dara-VRd in private hospital then referred to SGH for ASCT consolidation • Preference for natural conception (rather than sperm banking) for religious reasons

Treatment course

• Received 3 cycles Dara-VRD (Under Private Oncologist)= utilized all his financial resources • 2 further VRD cycles in SGH > VGPR M band 2 g/L • Autologous stem cell transplant • Lenalidomide maintenance for 2 years > stop for 3 years

Treatment Course

3x Dara-VRD 2x VRD

Melphalan 200mg/m2 ASCT

Jan 2020

Started on Len maintenance 10 > 25mg

June 2020

March 2020 Best response: VGPR

Reduced Len to 15mg as no change in VGPR status with Len 25mg for 8 cycles

Oct 2020

Sep 2020 M Band persisted at 2 g/L. BMAT: Flow: 0.04% atypical plasma cells. FISH negative.

Stopped Len maintenance

Sep 2021

Sep 2022

Aug 2021

Sep 2022

No M band but IFX positive

CR. IFX also negative (best response, no BMAT confirmation)

April 2023 present M band detectable 2g/L

Questions for Discussion Where access to CD38 monoclonal antibodies is limited by cost, how do we best apply current trial data to guide strategic use of these agents in standard risk NDMM? For patients with long life expectancy, what is the optimal maintenance regimen and duration to balance efficacy with considerations of 1. Family planning 2. Second primary malignancies 3. ‘Future proofing’ (i.e. preserving agents for later relapse)?

#1: Dr. #6 Dr. Tanapan Thamgrang Bangkok Thailand

IMF Asian Myeloma Network 5th Master Class Program

Case Sharing

Tanapun Thamgrang Division of Hematology, Department of Medicine Phramongkutklao Hospital Bangkok, Thailand

Case Sharing from Phramongkutklao Hospital • A 63-year-old man, government officer presented with foamy urine and leg edema for 6 weeks • U/D: T2DM (Last HbA1C 2 months ago= 6.7%, no DR), dyslipidemia, hypertensio n, SVD S/P PCI to LAD, OSA • PE: BMI 35 kg/m2, mild pallor, pitting edema 3+ both legs • Initial lab tests: • Hb 10.1 g/dL, Hct 30.8%, MCV 76.9 fL, RDW 15.9%, WBC 10400/µL (N 50%, L41%), platelet 344000/µL • UPCI 10.78, urine protein 24 hr = 7.67 g, cholesterol 414 mg/dL, LDL 305 mg/dL, Alb 1.

99 g/dL, Cr 0.84 mg/dL, Ca 7.82 mg/dL (9.84 mg/dL)

• Dx. Nephrotic syndrome • Renal biopsy:

Renal AL amyloidosis

• The glomeruli show moderate to severe matrix expansion with acellular eosinophilic amorph ous material (negative PAS and silver stain) and inhomogeneous glomerular basement memb rane thickening. Arterioles show focal acellular eosinophilic material deposits.

• The Congo red stain shows congophilic staining with apple green birefringence under p olarized light.

• Immunofluorescence shows lambda (3+) smudgy mesangial staining while kappa (trace) sm udgy mesangial staining.

Consult hematologist for type of amyloidosis and further investigation

Case Sharing from Phramongkutklao Hospital • SPEP: Monoclonal at B1 zone (M protein 0.4 g/dL); SFLC: kappa 17.41 mg/L, lambda 65.14 mg/L, ratio 0.26 (dFLC 47.7); IFE: IgA lambda monoclonal gammopathy; IgA level: 332 mg/dL (78-311) • β2-microglobulin 2.33 mg/L, LDH 408 U/L • Bone marrow biopsy: • Normocellular marrow with trilineage hematopoiesis, plasmacytosis, and a myloid deposition • Congo red stain is positive for amyloid • Immunostains show increased plasma cells 15% of marrow cellularity with lambda light chain predominant • FISH: positive deletion of 17p13 = 5.5% • MRI whole body: no abnormal marrow signaling, no plasmacytoma • EKG: low voltage in limb lead with antero-septal infarction • Cardiac MRI: cardiac amyloidosis is diagnosed.

• NT proBNP 11,991 pg/mL, Troponin T 102 ng/L • Multiple myeloma IgA lambda with systemic AL amyloidosis, R-ISS stage II, Revised Mayo stage II, Renal stage II (Transplant eligible)

Case Sharing from Phramongkutklao Hospital 70

65.14

“Hematologic response”

60 50 40

1st DaraVCd 40

6th DaraVCd in sCR

30

30 20

3rd DaraVCd

17.41 14.21 13.8

30.64

IFE: no paraprotein detected SFLC: k 9.24, L 7.84, ratio 14.8 1.18, dFLC 1.37

19.34

11.39 9.24 7.84

10 0 At diagnosis

3 months Kappa (mg/L)

0

0

5 months

7 months

Lambda (mg/L)

ASCT with melphalan 200 mg/m2 6/kg 0 Stem cell dose 2.29x10

M protein x 10^-2 g/dL)

12 months

Case Sharing from Phramongkutklao Hospital 600

584

Organ Response

Cardiac

Renal

Hepatic

≤30% ↓ in NT-proBNP from baseline

≤30% ↓ in proteinuria from baseline

≤30% ↓ in AP from baseline

Partial response

31% to 60% ↓ in NT-proBNP from baseline

31% to 60% ↓ in proteinuria from baseline

31% to 60% ↓ in AP from baseline

Very good partial response

>60% ↓ in NT-proBNP from baseline to nadir >400 pg/mL

>60% ↓ in proteinuria from baseline to nadir >200 mg/24 hr

>60% ↓ in AP from baseline to nadir >2 x LLN

Complete response

Nadir NT-proBNP ≤400 pg/mL

Nadir proteinuria ≤200 mg/24 hr

Nadir AP ≤2 x LLN

Organ progression

NT-proBNP progression (>30% and >300 pg/mL ↑) or troponin T progression (>33% ↑) or ejection fraction progression (≥10%309 ↓)

50% ↑ (≥1 g per day) of 24-hr urine protein to >1 g per day or 25% worsening of serum creatinine or creatinine clearance

50% ↑ of AP from nadir

No response

500

400

Organ responses before ASCT

300

200

168

154 143.8461538 119.91 107.826087 102

100

85 46.7 16.44

55.12605042 35.2

41.8972332 28.43

31.77083333 29.6

7.24

5.2

4.11

5 months

7 months (ASCT)

12 months

0

At diagnosis

3 months TropT (ng/L)

NT-proBNP x10^2 (pg/mL)

APL (IU/L)

UPCR x 10^-1

Case Sharing from Phramongkutklao Hospital Date

UPCR

U. Protein 24 Cr (mg/dL Trop-T (ng/ h ) L)

24/5/2023

212/72.8=2.9

4.96

0.75

18/7/2023

103/46.8=2.2

3.58

0.77

3/1/2024

0.83

2/7/2024

80/20.6=3.8

27/8/2024

442/123.9=3.

6

22/11/2024

498/78.1=6.4

5/1/2025

364/66.6=5.5

21/1/2025

332/85.9

18/2/2025

203/45.5

2.62

0.91

0.94

724 546

37.7

442

Remark 3/7/2023 ASCT Daratumumab maintenance x 19 cycle

328

0.93 0.97

6.2

28.43

NT-pro BNP (pg/ml)

31.9

Bone marrow biopsy: no plasma cell SFLC: 32.39/25.02 = 1.29 (dFLC 7.37) Ifx: polyclonal

- 19th Daratumumab - Only renal pr ogression (rena l biopsy confir med)

18.1 18.1

55.5% ↓

• Treatment: Continued VRD for 5 cycles 19.7partial response 264 pg/ml • Renal response:

1st VRD 19/3/2 025

Case Sharing from Phramongkutklao Hospital • Questions • What would be your preferred second-line treatment after Dara-V CD followed by daratumumab maintenance, in a patient with rena l-only progression?

• Would you consider a second autologous stem cell transplant (AS CT) in this situation? What about second-line maintenance?

• Would your treatment approach change if the patient had AL amy loidosis only, without MM?

#1: Dr. #7: Dr. Takeshi Yoroidaka RRMM after BCMA-CART Takeshi Yoroidaka Kanazawa University Hospital, Japan

2025/7/25 AMN Master class

Case presentation RRMM after BCMA-CART Takeshi Yoroidaka Kanazawa University Hospital, Japan

47 Years, Male IgG-κ type, ISS-I, R-ISS II, t(4;14)-, t(14;16)-, del(17p)-, 1q gainVRD 2cycles/DRd 2cycles ASCT(Mel200)/Len/Ixa

Regimen

PD

Best response

PD

sCR(Flow-MRD negative)

VGPR • lymphocyte apheresis • Bridging therapy with DKd

At initial diagnosis • hypercalcemia • renal impairment • Bone lesion

Since diagnosis (months)

0

DKd 1cycles

EPd 1cycle

56

57

58

Ide-cel 5.4×106 cells

47 Years, Male IgG-κ type, ISS-I, R-ISS II, t(4;14)-, t(14;16)-, del(17p)-, 1q gainEPd 1cycle

Regimen

(mg/dL) 6000

DKd 1cycle

PD

Lymphocyte Apheresis

IgG

Ide-cel • 5.4×106 cells infusion • Grade1 CRS • No ICANS

(mg/dL) 200 150

4000

100

Kappa

2000

50 0

0

BM:PC47%

BM:PC23%

Since diagnosis (months)

56

57

BM:MRD(-)

58

59

BM:MRD(-)

BM:MRD(+)

73

serum IFE(-)

47 Years, Male IgG-κ type, ISS-I, R-ISS II, t(4;14)-, t(14;16), del(17p)-, 1q gainEPd 1cycle

Regimen

(mg/dL) 6000

DKd 1cycle

PD

Ide-cel

Lymphocyte Apheresis

IgG

(mg/dL) 200 150

4000

100

Kappa

2000

50 0

0

BM:PC47%

BM:PC23%

Since diagnosis (months)

56

57

BM:MRD(-)

58

59

BM:MRD(-)

BM:MRD(+)

73

serum IFE(-)

Clinical Question Case summary: • 48 years old, male • t(4;14)-, t(14;16)-, del(17p)-, 1q gain• refractory: bortezomib, lenalidomide, ixazomib, Elotuzumab, pomalidomide • relapsed after Ide-cel (13 months later) with bone leision

1．What is the best option after Ide-cel relapse?

• Daratumumab+Carfilzomib+dex • radiation therapy • Belantamab-mafodotin • Elranatamab/Teclistamab • Talquetamab (not available now, in Japan)

Clinical Question Case summary: • 48 years old, male • t(4;14)-, t(14;16)-, del(17p)-, 1q gain• refractory: bortezomib, lenalidomide, ixazomib, Elotuzumab, pomalidomide • relapsed after Ide-cel (13 months later) with bone leision

2．Should allogeneic transplantation be considered as a strate gy for long-term survival?

#1: Dr. #8 Jing Xia Li

Case presentation

A Case of Primary Plasma Cell Leukemia with Coma as the Initial Symptom Secondary to Hyperammonemia Jing-Xia Li Dept. of Hematology, The First Affiliated Hospital, Sun Yat-Sen University

65 y.o. Male, back pain for 2 months

Plasma cell leukemia, with EMD

• CBC: WBC 13.71×109/L，NEUT 6.85×109/L， Hb 99g/L，PLT 93 ×109/L；

Ig: IgA 0.26g/L, IgG 3.54g/L, IgM <0.21g/L

• LDH 2071U/L

BM: 23% plasma cells; PB: 8% plasma cells

• β2MG: 8582.56ug/L

FCM: clonal PC restrictedly expressing cλ.

IF: IgD-λ; B-J protein: λ+

• ALB 32g/L, GLB 26g/L

C：2.32mmol/L

• Othet test: unremarkable.

R：119umol/L

• Ammonia: 185umol/L • Uro-Protein: mALB 319.89mg/L， λ chain 3021.6mg/L，κ chain 23.29mg/L.

A： 99g/L B：No obvious bone destruction. Soft tissue in lower abdomen, with increased metabolic activity: EMD? FISH: 1q21 amp (4copies), 1p32 del

Onset of disease

One cycle of PAD

65 y.o., Male. PCL (IgD-λ), 1q21 amp, 13q del Onset

CNS involvement

Plasma cell leukemia

Succumbed PAD

Back pain 2 mo Sudden coma →Hyperamonia

DaraKAD

DaraKAD

DaraKAD

Harvest T cell for BCMA-CAR-T Coma ←Encephaledema

T cell Expansion Failure ← Low lymphocyte (0.1-0.18 ×109/L)

→ Mubbling → VP shunt

254 196 143148 134

181 164168

106114

94

Ammonia(umol/L)

Months since diagnosis

0

CSF exam:

106 41

50 58

32

15 14

2

176mmH2O WBC 1*106/L， Prot 2010mg/L

14

3

4

5

7

• Extremely rare presentation: o Underlying mechanism?

Discussion

• Aggressive biological behavior, short DOR, and poor prognosis: o CAR-T cell therapy? o Bi-specific antibodies? Tri-specific antibodies? o Timing & combination? o Other...

Thank you for your attention!

Jing-Xia Li, jxleeee@qq.com Dept. of Hematology, The First Affiliated Hospital, Sun Yat-Sen University

#1: Dr. #9 Dr. Julian Jomell MM BC

Multiple myeloma with Breast Cancer Dr. Julian Jomell

Synchronous presentation of myeloma with Breast Cancer Known case of Breast Cancer – 2022; AC x 6cycles from June to October 2022 Currently maintained on Letrozole 2.5mg tab OD Patient was initially well until follow-up last May 2025 noted with pancytopenia associated with • Hgb 74 Hct 24 WBC 3.33 (N-33, L-61, M-2, E-1) Plt 58 • Hgb 74 Hct 24 WBC 3.37 (N-34, L-55, M-3, E-1) Plt 59 • Crea 1.2 K 4.9

BMA: Plasma cell myeloma The core biopsy shows a markedly hypercellular bone marrow with 8090% overall cellularity. There are infiltrate of plasma cells in large aggregates comprising approximately 50-60% of the marrow cellularity.

Erythrogranulopoiesis is present with maturation with a myeloid to erythroid ratio of 3:1. Megakaryocytes with medium-to large-sized hypolobated forms are seen. Special stain shows absent to mild reticulin fibrosis (Grade 0)

SPEP: Consistent with monoclonal gammopathy; Monoclonal peak concentration 53.4% (6.3 g/dl) B2 microglobulin 4.1 mg/L (1.0-2.4mg/L) Albumin 3.3 TP 11.8 g/dl FISH for Myeloma: (+) 1q21 amplification Immunohistochemistry results • CD 138: Positive diffuse and strong cytoplasmic membrane expression in plasmic cells comprising 50-60% of the marrow cellularity • Kappa and Lambda: Positive, strong, cytoplasmic expression of KAPPA is seen in the majority of the neoplastic plasma cells supportive of KAPPA restriction

Questions • Which regimen is best to be used with the case given with poorrisk cytogenetic results?

#1: Dr. #10. Amrit Dhar, India

Case Presentation AMN 2025 Teclistamab- Dosing and challenges Our Experience with Penta Refractory MM

Dr Amrit Dhar MBBS,MD SR-2, Department of Medical Oncology and Hematology Tata Memorial Hospital, Mumbai,India

Brief History - Mrs X •

63 y/o, Female, No known comorbidities

•

Baseline complaints: Low backache in 2020

•

Diagnosed as: ✓ Multiple Myeloma- Lambda Light chain disease ✓ C-R+A+B+; ISS-II ✓ CTG: 13q deletion ✓ Baseline SPEP- Distorted beta region, Free Lambda 8620, Free Kappa 21.0 ✓ K/L ratio: 0.002

Prior Lines of Treatment

1. 1# VCD f/b 6# VRD —> Achiveved CR 2. Auto HSCT ( HD Melphalan 200 mg/m2) f/b Lenalidomide maintainance

3. DFI 3 years

Contd…

4. Dara-VD —>Progression in 6 months 5. KPd—-> Progressed in 3 months ✴ Screened for BCMA-CART trial - Not eligible ✴ Two PI, Two ImiDs and 1 AntiCD38 had been used ✴ Discussed further options with patients •

Planned for Teclistamab

Inital Step up dosing 0.06 mg/kg D1 f/b 0.3mg/kg D3 f/b 1.5 mg/kg weekly

Response assessment

BM assessment post C1 Teclistamab

Post cycle 3 Teclistamab

Toxicities and Current status • CRS Grade 1 in week 1 only.

• LRTI- Likely viral in week 3 • Rest no issues • Recieved IVIG concurrenlty [IgG: 320] • Maintains CR

Challenges with Teclistamab Questions for experts

1. Predictors of Outcomes in Teclistimab?

1. Role of T-cell subset analysis?

2. sBCMA as a marker of response?

2.Infectious complications? Are they different from CART? 3.How to dose post-achievement of CR? 4. Approach to Teclistimab failure?

5.Role of BCMA-CART post teclistimab?

Acknowlegdement

• Dr Bhausahab Bagal, DM, Professor, Hematology Unit, Department of Medical Oncology,TMH

• Department of Medical Oncology • All staff and colleagues

Thank you for your patience

#1: Dr. #11 Celene Wong, Hong Kong

Case presentation IMF AMN Master Class 2025 • 49/M IgG kappa myeloma

• Diagnosed in Thailand in 4/2022. Presented with PRB • Noted anemia and thrombocytopenia • No renal impairment nor hypercalcemia • SPE: IgG kappa 52.5 g/L • SFLC: kappa 399, K/L ratio: 167.65 • BM: 69% plasma cells • FISH: Gain in CKS1B (1q21), loss of CDKN2C (1p32.3) • B2M: 9.81 • R-ISS stage II

SW Wong (Hong Kong)

• DaraKT x 2 cycles, Dara-KRCD, DaraVTD x 2 cycles • DaraRD x 2 cycles  PD with extensive extramedullary involvement including NP, neck LN, liver, duodenum, paraspinal soft tissue mass • DT-PACE x 3 cycles 60 • Disease progressed with extensive disease involving NP, cervical LN, right hilar mass; peritoneal mass and soft tissue mass overlying T10 and T8, bilateral humeri, femurs, spine.

52 50

Dara-KT, DaraKRCD, Dara VTD, DaraRD

40

30

20

10

17

12

DT-PACE

18

10

7

15

PCD 16 Teclistamab cycle 1-15 3 0

0

1

1

• PET CT after 6 months of teclistamab (1/2024) • previous R NP mass, cervical LN, R hilar mass, peritoneal mass, peritoneal deposit, paraspinal soft tissue mass, epidural mass from T9-11 resolved • Presented with 3 episodes of transient left sided numbness (11/2024) • Transcranial doppler: unremarkable • EEG: No epileptiform discharge • Contrast MRI brain:Suspected diffuse supratentorial leptomeningeal enhancement and nodular thickening.

• CSF shows involvement by plasma cell myeloma

• PET-CT (12/2024):no disease involvement • Managed as isolated CNS relapse

11/2024 CNS relaps e (leptom eningeal dis eas e) while on teclis tam ab

5/2025 CNS relaps e (both leptom eningeal and parenchym al dis eas e)

12/2024 Switch to Pom / Dex and s tarted IT chem otherapy

received Intrathecal chemotherapy with IT MTX and hydrocortisone CSF clear for plasma cell after 4 doses of IT chemotherapy then patient decline further IT chemotherapy in view of intolerance to post-LP headache Withheld teclistamab and switched to Pomalidomide and Dexamethasone since 12/2024 Patient developed headache in 5/2025 CSF shows involvement by plasma cell myeloma MRI brain (6/2025): - Leptomeningeal enhancement are detected at bilateral parasagittal and bilateral cerebral hemispheres.

- Multiple focal enhancing cerebral lesions have been detected, most likely indicative of brain metastasis.

These are associated with perilesional vasogenic edema.

Discussion With Penta-refractory multiple myeloma with extensive extramedullary disease, received 15 cycles of teclistamab , then developed CNS relapse (currently on IT chemotherapy and pomalidomide/dexamethasone up to 7 cycles, pending workup for PET-CT and BM also discussed with oncologist for craniospinal RT) 1.

At 1st isolated CNS relapse while on teclistamab, should we continue teclistamab for systemic disease control?

2.

If workup confirm both systematic and CNS relapse, what will be the possible treatment option?

3.

If it is an isolated CNS relapse and the CNS disease is under control, what should be next line of treatment?

Wrap Up & Announcements Thank you to our Sponsors!

Scan to share your thoughts and feedback with us