5  Tumor Board: Evolving Myeloma Treatment Paradigm

5.1 Session Overview

Day 1, 2:00–3:15 p.m.

This three-speaker tumor board works through the myeloma continuum using illustrative cases [slide p.1]. Gin Gin Gan (Universiti Malaya, Kuala Lumpur) opens with a 64-year-old, standard-risk, transplant-eligible NDMM case and walks through induction choices and maintenance [slides p.4–17]. Shaji Kumar (Mayo Clinic, Rochester) then tackles an 82-year-old frail transplant-ineligible patient, covering frailty assessment, Isa-VRd/D-Rd/Tec-Dara data, and how to individualize intensity by risk and fitness [slides p.31–44]. Hang Quach (St Vincent’s Hospital, Melbourne) closes with a 72-year-old fit patient relapsing with extramedullary disease and t(11;14)/del(17p)/1q21, using the case to highlight MajesTEC-3, RedirecTT-1, STEM (cevostamab post BCMA CAR-T), IBI3003 and Viber-M [slides p.45–76].

5.2 Speaker Spotlight

  • Gin Gin Gan, MD — Universiti Malaya, Kuala Lumpur. Expert in myeloma care delivery in resource-variable settings; focuses on equitable access to novel therapies in Southeast Asia.
  • Shaji Kumar, MD — Mayo Clinic. Internationally recognized leader in myeloma therapeutics, MRD-guided strategies, and clinical trial design.
  • Hang Quach, MBBS, MD — St. Vincent’s Hospital, Melbourne. Pioneer in translating bispecific antibody and CAR-T data into real-world Asia-Pacific practice.

5.3 What’s New in 2025–2026

5.3.1 Transplant-Eligible NDMM: Induction and the CASSIOPEIA/PERSEUS Benchmark

Gan framed the session with a 64-year-old man with standard-risk IgG-kappa myeloma (Hb 90 g/L, creatinine 1.8 mg/dL, ISS II-equivalent, FISH normal) and asked the audience to choose induction [slide p.4]. She grounded the decision in the ASCO–Ontario Health living guideline, which tabulates CASSIOPEIA (D-VTd), GRIFFIN/PERSEUS (D-VRd) and GMMG-HD7 (Isa-VRd) head-to-head against triplets [slide p.7]. Long-term CASSIOPEIA showed a PFS HR of 0.61 and an OS HR of 0.55 favoring D-VTd, and PERSEUS delivered ≥CR in 87.9% versus 70.1% and MRD-negativity in 75.2% versus 47.5% with D-VRd versus VRd [slide p.8].

Dytfeld’s COBRA phase 3 trial (KRd vs VRd; n=250, IMWG frailty <2) was presented in detail [slides p.9–14]. Key results at a median 53-month follow-up:

  • ORR 94.4% (KRd) vs 91.1% (VRd); ≥CR 70.6% vs 53.2% (OR 2.11, p=0.005) [slide p.11]
  • Median PFS not reached vs 48.8 months (HR 0.57, 95% CI 0.37–0.88, p=0.0095) [slide p.11]
  • Benefit preserved in the high-risk subgroup (HR 0.52) though underpowered [slide p.12]
  • MRD-negative ≥CR at 12 months: 31.0% vs 17.7% at 10−5 and 19.0% vs 7.3% at 10−6 [slide p.13]
  • OS identical at 53 months (HR 1.05) — a deeper response without an OS signal yet [slide p.14]

5.3.2 Post-ASCT Maintenance: From Lenalidomide Alone to D-R and KRd

After the illustrative patient received VRd × 4 → ASCT, Gan turned to maintenance [slides p.15–16]. The ASCO guideline table positions ATLAS (KRd → R), FORTE (KR) and AURIGA (D-R) against lenalidomide alone [slide p.17]. Updated ATLAS data (median follow-up 69 months) showed 4-year PFS of 67.5% for KRd versus 38.0% for R (p<0.0001), with median OS not reached versus 82.2 months [slides p.18–19].

Kumar walked the audience through AURIGA, the phase 3 trial of D-R versus R maintenance in DARA-naïve, MRD-positive post-ASCT patients (n=200) [slides p.20–28]. Highlights:

  • MRD-negative conversion at 10−5: 60.6% (D-R) vs 29.7% (R); at 10−6: 36.4% vs 13.9% [slide p.23]
  • Sustained ≥12-month MRD negativity at 10−6: 19.2% vs 2.0% (OR 11.75) [slide p.24]
  • PFS HR 0.55 (95% CI 0.33–0.91, p=0.0183); 36-month PFS 76.8% vs 61.4% [slide p.26]
  • High-risk patients still relapsed rapidly regardless of arm, reinforcing the 10−6 threshold as the more discriminating endpoint [slide p.25]
MRD as a Decision Tool

AURIGA reframes MRD from a prognostic marker into a dynamic, treatment-guiding endpoint: depth (10−6), sustainability (≥12 months), and conversion under therapy now stratify long-term risk better than a single time point [slides p.22, 27].

5.3.3 Transplant-Ineligible NDMM: Quadruplets, Dose Adaptation, and Frailty

Kumar opened with an 82-year-old woman with IgA-kappa myeloma, t(4;14), monosomy 13, Hb 10.9 g/dL, and creatinine 1.4 mg/dL [slide p.31], then asked why age matters — comorbidities, frailty, altered drug metabolism, limited support, and mobility [slide p.33]. The IMWG frailty score (age, Charlson, ADL, IADL) stratifies patients as fit / unfit / frail, and frail patients suffer greater toxicity and shorter survival [slide p.49].

Evidence surveyed:

  • RVd-lite (O’Donnell et al, BJH 2018): 9-cycle dose-adapted induction, ORR 86%, ≥VGPR 66% [slide p.34]
  • MAIA D-Rd: median PFS not reached vs 34 months with Rd; 7-year OS 53.1% vs 39.3% with D-Rd (HR 0.67) [slide p.35]
  • IMROZ Isa-VRd vs VRd in TI NDMM: 60-month PFS 63.2% vs 45.2% (HR 0.596, p=0.0005); sustained ≥12-month MRD-negativity 46.8% vs 24.3% [slide p.36]
  • CEPHEUS D-VRd vs VRd: ≥CR 81.2% vs 61.6%, MRD-negativity 60.9% vs 39.4%, PFS HR 0.57 [slide p.37]
  • BENEFIT (IFM 2020-05) Isa-VRd vs Isa-Rd: sustained MRD-negativity at 10−6 28% vs 10%; MRD at 24 months 34% vs 18% favoring the quadruplet [slides p.38–41]
  • IFM 2021-01 TecLille cohort A Tec-Dara in TNE NDMM (n=37; chemo-free “all-antibody” regimen): 100% ≥VGPR, 100% MRD-negative at 10−6 at 6 months, PFS and OS 100% at median 10.3 months; grade ≥3 infections 14% with systematic IVIG prophylaxis; no grade ≥3 CRS, no ICANS [slides p.43–46]
  • UK-MRA FiTNEss (Myeloma XIV) ixazomib-Rd with standard versus IMWG-frailty-adjusted dosing (n=733): frailty-adapted dosing reduced early treatment cessation and improved PFS/OS in the UNFIT group but offered no benefit in the FRAIL cohort — reinforcing that dose modification alone cannot fix true frailty [slides p.50–53]

Kumar’s synthesis slide showed risk and frailty as opposing triangles determining the depth (quadruplet vs triplet vs doublet), the role of ASCT, and the choice of doublet versus single-agent maintenance [slide p.54].

5.3.4 Relapsed/Refractory Myeloma: Bispecifics, CAR-T and Novel Combinations

Quach presented Mr JD, a 72-year-old fit patient relapsing 17 months post VRd/ASCT/R-maintenance with a T7 paraspinal plasmacytoma (4.5 × 3.2 × 3.8 cm), a 2 cm subcutaneous nodule, and FISH showing t(11;14), del(17p) and 1q21 gain [slides p.55–57]. The Dimopoulos/Myeloma Australia algorithm stratifies next-line choice by prior exposure and refractoriness to CD38 mAbs and lenalidomide, emphasizing early use of the most effective available therapy rather than sequential reservation [slide p.59].

MajesTEC-3 (Mateos et al., ASH 2025) — phase 3 teclistamab + daratumumab versus DPd/DVd in RRMM with 1–3 prior lines (n=587) [slides p.60–63]:

  • 36-month PFS 83.4% vs 29.7% (HR 0.17, 95% CI 0.12–0.23, p<0.0001)
  • 36-month OS 83.3% vs 65.0% (HR 0.46, p<0.0001)
  • ORR 89.0% vs 75.3%; ≥CR 81.8% vs 32.1%; MRD-negativity 58.4% vs 17.1%
  • Grade 3–4 infections 54.1% vs 43.4%; CRS 60.1% (all grade), 0% grade 3–4; ICANS 1.1%
  • PFS benefit consistent across all subgroups, including high-risk cytogenetics, prior anti-CD38 exposure, ISS III, and baseline soft-tissue plasmacytomas

RedirecTT-1 (Usmani et al., updated phase 2) — talquetamab + teclistamab in triple-class-exposed RRMM with true extramedullary disease (EMD) (n=90) [slides p.64–66]:

  • EMD itself confers an 87% lower likelihood of response to real-world SOC [slide p.65]
  • ORR 78.9%, ≥CR 53.3%; median PFS 15.0 months; 12-month DOR 62.1%; 12-month OS 73.8%
  • Responses observed regardless of EMD location
  • Grade ≥3 infections ~33%; CRS 77.8% all grade, no grade ≥3; ICANS uncommon

STEM trial (Cohen et al., Penn; NCT05801939) — phase 2 cevostamab (anti-FcRH5 bispecific) consolidation starting 10–12 weeks after ide-cel or cilta-cel, with MRD-adaptive stopping [slides p.67–69]:

  • n=27, median 4 prior lines, ~75% triple-class refractory, 19% EMD
  • CR rate rose from 63% pre-cevostamab → 81% at C8D1 → 93% at 1 year post-CAR-T
  • 1-year MRD-negative CR rate 93%; grade 3–4 infections 15%; no grade ≥3 CRS; no ICANS during cevostamab
Clinical Pearl: Sequencing BCMA and GPRC5D

Both the Tec-Tal combination (RedirecTT-1) and post-CAR-T cevostamab consolidation (STEM) exploit non-cross-resistant targets (BCMA, GPRC5D, FcRH5) to re-engage T cells and eliminate residual antigen-low clones, pointing toward combination/sequencing strategies rather than linear single-target escalation [slides p.66, 69].

IBI3003 — first-in-human phase 1 of a GPRC5D × BCMA × CD3 trispecific antibody (Li et al., presented with Quach as co-author) [slides p.70–72]:

  • n=39; median 4 prior lines; 100% triple-class exposed, 51% penta-class exposed; 46% EMD; 64% high-risk
  • At ≥120 μg/kg QW: ORR 83.3%; with EMD 80.0%; with prior BCMA/GPRC5D therapy 77.8%
  • 100% MRD-negative among evaluable ≥CR patients
  • Grade ≥3 CRS 0%; ICANS 6.1% (all grade 1–2); grade ≥3 infections 28.2%

Viber-M (ALLG MM25) (Sim et al.) — Australasian phase Ib/II of venetoclax + iberdomide + dexamethasone in t(11;14) RRMM with 1–2 prior lines, rationalized by BCL-2 dependence of the t(11;14) clone and the CELMoD activity of iberdomide [slides p.73–76]:

  • Planned interim (first 20 patients; 65% lenalidomide-refractory, 20% daratumumab-refractory): ORR 80%, ≥VGPR 25%, ≥CR 5%
  • Lenalidomide-refractory: ORR 85%; daratumumab-refractory: ORR 75%
  • Neutropenia 50%; infections 35% (grade 3–4 in 10%)
Talquetamab and GPRC5D: Unique Toxicity Profile

GPRC5D-targeting therapy (talquetamab, IBI3003’s GPRC5D arm) produces distinct nail, skin and taste/oral adverse events not seen with BCMA-directed agents [slides p.66, 72]. Counsel patients up front and monitor for dysgeusia, nail dystrophy and xerosis.

5.4 Treatment Algorithm

Table 5.1: Myeloma treatment sequencing algorithm synthesized from the slide deck
Setting Recommended Approach
NDMM-TE, fit D-VRd or Isa-VRd induction × 4 –> ASCT –> 2 cycles consolidation –> lenalidomide-based maintenance (R alone, D-R, or KR per ASCO–Ontario guideline) [slide p.30]
NDMM-TI, quadruplet-suitable D-VRd (CEPHEUS) or Isa-VRd (IMROZ/BENEFIT) continuous; Tec-Dara emerging as chemo-free option in selected patients (TecLille) [slides p.30, 36–46]
NDMM-TI, not quadruplet-suitable D-Rd (MAIA) or VRd; consider RVd-lite and frailty-adjusted dosing for UNFIT patients [slides p.30, 34–35, 50–53]
1st relapse, fit Tec-Dara (MajesTEC-3, HR 0.17 for PFS); alternative: cilta-cel or anti-CD38-based triplet per prior exposure [slides p.59–63]
RRMM with EMD Talquetamab + teclistamab (RedirecTT-1) — ORR ~79%, responses regardless of EMD site [slides p.64–66]
Post-BCMA CAR-T consolidation Cevostamab q3wks × 8, MRD-adapted stopping (STEM) [slides p.67–69]
t(11;14) RRMM Venetoclax-based combination (Viber-M: Ven + Iberdomide + dex) [slides p.73–76]
Triple-class exposed GPRC5D × BCMA × CD3 trispecific (IBI3003) in clinical trial [slides p.70–72]
Clinical Pearl: Sequencing BCMA and GPRC5D

After BCMA-directed therapy failure (bispecific or CAR-T), switching to the GPRC5D target with talquetamab can recapture responses. Alternating targets avoids antigen-escape resistance and maintains immunotherapy efficacy across lines.

5.5 Clinical Pearls

5.5.1 Five Key Takeaways

  1. Anti-CD38 + PI + IMiD quadruplets are the preferred induction for fit TE and TI NDMM patients under 80. Across PERSEUS, CEPHEUS, IMROZ and BENEFIT, quadruplets drive higher MRD-negativity that translates into longer PFS, and early signals point to an OS benefit [slides p.8, 36–41, 44].
  2. Depth and sustainability of MRD negativity — particularly at 10−6 — now drive maintenance decisions. AURIGA showed that D-R tripled sustained ≥12-month MRD-negativity at 10−6 versus R alone, and high-risk patients who achieved only 10−5 negativity still relapsed rapidly [slides p.23–25, 28].
  3. Individualize intensity to risk and frailty, not chronological age. Treatment depth should scale with cytogenetic risk and inversely with frailty; FiTNEss showed dose adaptation helps UNFIT but not FRAIL patients, so truly frail patients need better-tolerated regimens rather than dose reduction alone [slides p.53–54].
  4. At first relapse, Tec-Dara (MajesTEC-3) sets a new benchmark — HR 0.17 for PFS versus DPd/DVd — with benefit preserved across high-risk, EMD and prior anti-CD38 subgroups [slides p.61–63]. Use the most effective immunotherapy early rather than reserving it.
  5. For late lines, combine non-cross-resistant T-cell engagers. Talquetamab + teclistamab (RedirecTT-1) in EMD, cevostamab consolidation post BCMA CAR-T (STEM), the GPRC5D × BCMA × CD3 trispecific IBI3003, and venetoclax + iberdomide for t(11;14) (Viber-M) all illustrate that sequential/combination T-cell engagement and biomarker-selected therapy are now realistic options for triple-class-exposed disease [slides p.66, 69, 72, 76].
Access Considerations in Southeast Asia

Gan highlights that variable drug availability across SE Asian countries necessitates flexible algorithms. VRd-based triplets remain the backbone where anti-CD38 access is limited; telemedicine tumor boards can bridge expertise gaps across the region. [editorial]

Infection Prophylaxis with Bispecifics and Cevostamab

The TecLille (Tec-Dara) cohort achieved only 14% grade ≥3 infections with systematic IVIG prophylaxis [slide p.46]; STEM similarly reported 15% grade 3–4 infections with fixed-duration cevostamab and no ICANS [slide p.69]. Routine IVIG (target IgG >400 mg/dL), PJP and herpesvirus prophylaxis, and vaccination before bispecific initiation are now standard of care. [editorial]

5.6 Key References

  1. Hicks LK, et al. Treatment of Multiple Myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline. J Clin Oncol. 2025;JCO-25-02587. [slides p.7, 17, 30]
  2. Sonneveld P, et al. Daratumumab, bortezomib, lenalidomide and dexamethasone for newly diagnosed transplant-eligible multiple myeloma (PERSEUS). N Engl J Med. 2024;390:301–313. [slide p.8]
  3. Moreau P, et al. Long-term follow-up of CASSIOPEIA (D-VTd vs VTd). Lancet Oncol. 2024;25(8):1003–1014. [slides p.8, 16]
  4. Dytfeld D, et al. Carfilzomib, lenalidomide and dexamethasone versus VRd in NDMM: COBRA phase 3 results. ASH 2025 (oral). [slides p.9–14]
  5. Dytfeld D, et al. Carfilzomib, lenalidomide and dexamethasone versus lenalidomide after ASCT (ATLAS): primary analysis. Lancet Haematol. 2026;13:e241–e253. [slides p.17–19]
  6. Badros A, et al. Daratumumab with lenalidomide as maintenance after transplant in NDMM: the AURIGA study. Blood. 2025;145:300–310. [slides p.20]
  7. Chung A, et al. MRD dynamics in post-transplant NDMM on D-R versus R maintenance: AURIGA update. ASH 2025 (oral). [slides p.21–28]
  8. Facon T, et al. Daratumumab plus lenalidomide/dexamethasone in transplant-ineligible NDMM (MAIA 7-year update). Lancet Oncol. 2021;22:1582–1596; EHA 2024 update. [slide p.35]
  9. Facon T, et al. Isatuximab plus VRd in transplant-ineligible NDMM (IMROZ). ASCO 2024. [slide p.36]
  10. Usmani SZ, et al. Daratumumab plus VRd in transplant-ineligible NDMM (CEPHEUS). Nat Med. 2025;31:1195–1202. [slide p.37]
  11. Leleu X, et al. Isatuximab plus lenalidomide/dexamethasone with or without bortezomib in TI NDMM (IFM 2020-05 BENEFIT). Nat Med. 2024;30:2235–2241. [slides p.38–41]
  12. Manier S, et al. Teclistamab plus daratumumab in elderly TNE NDMM: IFM 2021-01 TecLille cohort A. ASH 2025, Abstract #367. [slides p.43–46]
  13. Pawlyn C, Cook G, et al. IMWG frailty-score-adjusted dosing in NDMM: UK-MRA FiTNEss (Myeloma XIV). ASH 2024. [slides p.50–53]
  14. Palumbo A, et al. Geriatric assessment predicts survival and toxicities in elderly MM patients: IMWG frailty score. Blood. 2015. [slide p.49]
  15. Mateos MV, et al. Teclistamab-daratumumab versus DPd/DVd in RRMM (MajesTEC-3 phase 3). ASH 2025; N Engl J Med. 2025. [slides p.60–63]
  16. Usmani SZ, et al. Talquetamab plus teclistamab in RRMM with extramedullary disease: RedirecTT-1 updated phase 2. ASH 2025. [slides p.64–66]
  17. Cohen AD, et al. Phase 2 study of cevostamab consolidation following BCMA CAR-T: the STEM trial. ASH 2025; NCT05801939. [slides p.67–69]
  18. Li J, et al. First-in-human phase 1 of IBI3003, a GPRC5D × BCMA × CD3 trispecific antibody, in RRMM. ASH 2025, Abstract #702. [slides p.70–72]
  19. Sim S, et al. Viber-M (ALLG MM25): venetoclax + iberdomide + dexamethasone in t(11;14) RRMM. ASH 2025. [slides p.73–76]
  20. Dimopoulos MA, et al. Treatment of relapsed refractory multiple myeloma. Nat Rev Clin Oncol. 2025;22:680–700; Myeloma Australia RRMM Clinical Practice Guideline 2022. [slide p.59]
  21. O’Donnell EK, et al. RVd-lite in transplant-ineligible NDMM. Br J Haematol. 2018;182:222–230. [slide p.34]