Al-Ola A Abdallah: 10 ASH Abstracts from ASH2025

Al-Ola A Abdallah, Associate Professor and Plasma Cell Disorder Program Director of the Division of HMCT at the University of Kansas Medical Center, shared 10 ASH Abstracts from ASH2025:

1.st ASH Abstract

“ASH Abstract ASH2025 OL-101, a BCMA/GPRC5D dual-targeting autologous CAR-T for relapsed/ refractory multiple myeloma (R/R MM): Results from a Phase I study from 1/New bispecific CAR-T for multiple myeloma! OL-101 targets both BCMA & GPRC5D using VHH binders to overcome antigen escape — a major hurdle for R/R MM. Preliminary phase 1 data (NCT06644118) just dropped.

Study design:

• Phase I, first-in-human trial •Dose escalation (1.0, 2.0, 1.5 ×10⁶ cells/kg)
• 10 pts with ≥3 prior lines (median 5)
• All triple-class exposed (PI, IMiD, anti-CD38)
• 30% had prior BCMA/GPRC5D therapy.

Safety:

• CRS in all pts (60% grade 1–2; 40% ≥grade 3)
• One DLT (grade 4 CRS) at 2.0×10⁶, fully resolved
• No ICANS observed
• Other grade ≥3 AEs: neutropenia (90%), thrombocytopenia (80%), anemia (30%)

After updating CRS management, no further grade 4 CRS occurred. Median CRS onset: Day 2; duration ~6.5 days. No grade ≥3 infections. Safety profile = manageable & consistent with CAR-T expectations.

Efficacy (as of Jul 30, 2025):

• ORR = 100% (!)
• ≥VGPR = 70%
• ≥CR = 40%
• Responses deepened over time
• MRD negativity (10⁻⁵) in all 10 pts by Day 28 and ongoing

By dose:

• DL1: 67% ≥VGPR, 33% ≥CR
• DL2: 83% ≥VGPR, 50% ≥CR
• Deeper responses at higher dose

Tough-to-treat groups:

• Extramedullary disease: 75% ≥VGPR, 50% ≥CR
• Prior BCMA/GPRC5D therapy: all responded (1 sCR, 2 PR) OL-101 active even post-targeted relapse!

Cell kinetics:

• Peak expansion: Day 10–21
• Median: 1.29×10⁵ copies/μg DNA
• CAR-Ts persisted ≥12 weeks

OL-101 = dual BCMA/GPRC5D VHH CAR-T

• 100% ORR & MRD negativity
• Manageable CRS, no ICANS
• Activity in BCMA/GPRC5D-exposed & EMD pts

Title: OL-101, a BCMA/GPRC5D dual-targeting autologous CAR-T for relapsed/ refractory multiple myeloma (R/R MM): Results from a Phase I study

2nd ASH Abstract

New data alert! A novel biparatopic nanobody-based BCMA CAR-T combined with pomalidomide shows promising potency for RRMM: In-vitro characterisation and phase 1 dose-escalation study. Here’s what you need to know. Another study from China 1/ Why this matters: RRMM remains tough to treat. Current BCMA CAR-T therapies work well—but many patients still relapse. Adding pomalidomide (an IMiD) could boost CAR-T performance.

What’s new? Researchers engineered a biparatopic nanobody CAR that binds two different BCMA epitopes at once, aiming for stronger tumor targeting and more durable responses.

In-vitro highlights:

•  Greater cytotoxicity vs commercial cilta-cel (Carvykti)
•  Maintained killing across 5 tumor re-challenge cycles
•  Pomalidomide ↑ stem/central memory T cells
•  Sustained killing boosted by 1.8× within 48h

Clinical trial design:

Single-center, phase 1, 3+3 dose escalation. Patients received CAR-T at:

•  DL1: 0.75×10⁶/kg
•  DL2: 1×10⁶/kg
•  DL3: ≥1.5×10⁶/kg

Plus pomalidomide 1–2 mg/day as maintenance

Who was treated?

16 infused patients (13 MM, 3 PCL)

Median age: 63

• ~69% had extramedullary disease
• ~69% were triple-refractory
• Median prior therapies: 4 lines
• A very heavily pretreated population.

Safety:

•  CRS in 93% (Grade ≥3: only 6.7%)
•  ICANS Grade 1 in 13%
•  No dose-limiting toxicities MTD = DL2 (1×10⁶/kg)

Efficacy:

Among 14 evaluable patients:

•  ORR: 100% • CR: 57% (8/14)
•  MRD negativity: 93% Deep responses even in refractory disease.

Dose matters:

DL2 showed the highest CR rate (71%) and highest CAR expansion (median 22,688 copies/µg gDNA).

This was selected as the RP2D.

Disease site matters, too:

•  Medullary-only disease: 100% CR, higher CAR expansion
•  Extramedullary disease: 44% CR Suggests disease distribution influences CAR-T performance.

Survival outcomes:

One-year:

•  PFS: 63.6%
•  OS: 69.1% Promising durability for a phase 1 RRMM cohort.

Takeaway:

This biparatopic BCMA CAR-T + pomalidomide combo shows:

• Superior in-vitro potency
• Manageable safety
• Deep MRD-negative responses

Next stop → Phase 2 evaluation.

Title: Combined biparatopic nanobody-based B cell maturation antigen chimeric antigen receptor T cell therapy and pomalidomide for relapsed or refractory multiple myeloma: In-vitro characterisation and phase 1 dose-escalation study

Presentation ID 253

From ASH25 Day 3

Thread: Phase 2 Study of Aponermin + KT-DECP in RRMM with EMD a study from China Kudus for the group to design a study focusing on EMD

RRMM with extramedullary disease (EMD) remains a high-risk population (3-yr OS ≈ 58%). Aponermin (Apo), a DR4/DR5 agonist, activates the extrinsic apoptosis pathway via caspase signaling. This trial evaluated Apo + KT-DECP in RRMM + EMD.

Study Design

• Multicenter, single-arm phase 2 (NCT05013190)
• Planned N=31; current N=23 •EMD confirmed per IMWG
• Apo-KT-DECP for 4–6 cycles; RT added if <CR
• Primary endpoint: ORR after 2 cycles
• Secondary: CR, ≥VGPR, time to response (TOR), safety

Patient Characteristics

• Median age: 62 yrs
• Prior lines: 3 (range 1–9)
• 43.5%: ≥3 EMD sites
• 60.9%: mixed bone-independent + paraskeletal lesions
• 30.4%: large EMD ≥5 cm
• High-risk cytogenetics: 37.5%
• Anaplastic/blastoid: 4 pts
• Malignant pleural effusion: 2 pts
• TCR: 56.5%
• No prior BCMA exposure

Efficacy

• Median follow-up: 7.5 mo
• Median PFS: Not reached
• 5-mo PFS: 77%
• ORR after 2 cycles: 90% (18/20)
• Best responses:
• ≥VGPR: 30%
• ≥CR: 25% (including 2 pts post-RT)
• Rapid onset: Median TOR = 0.5 mo Apo-KT-DECP produced fast and deep responses in a very high-risk cohort.

Safety

Any-grade AEs: 78.3% Most common:

• Thrombocytopenia: 65.2%
• Granulocytopenia: 56.5%
• Infection: 34.8%
• TLS: 8.7% Grade 3/4:
• Granulocytopenia: 17.4%
• Thrombocytopenia: 13.0%
• Pneumonia: 17.4% Overall, manageable toxicity profile.

Conclusion

• The Aponermin + KT-DECP regimen shows:
• Rapid responses
• Deep responses (↑CR/VGPR)
• Promising PFS
• Acceptable toxicity

A promising option for RRMM with EMD, a particularly challenging subgroup.

Title: Phase 2 study of aponermin +kt-decp in patients(pts) with Relapsed/Refractory multiple myeloma and extramedullary disease

presentation ID 2280

4th ASH abstract in myeloma

BCMA CAR-T in Newly Diagnosed, Transplant-Ineligible Myeloma (CAREMM-001 Study) from China

•  Study Design (NCT05860036) Single-arm, phase 2
• Pts ineligible for ASCT due to age, frailty, comorbidities, or failed mobilization
• 3–4 cycles of VRd → lymphodepletion → single infusion of academic BCMA CAR-T (3×10⁶ cells/kg)
• Consolidation + lenalidomide maintenance Primary: Safety + MRD− Secondary: CR, PFS, OS, DOR

Patients Apr 2023–Dec 2024 40 enrolled, 36 infused Median age: 68 yrs High-risk disease: • 45% ISS III • 38.5% ultra-high-risk (EMD, CPC ≥2%, or double-hit cytogenetics)

Efficacy

At 12.8-mo median follow-up: 100% MRD-negative at Day 28 (sustained in all pts!) ORR 100% 88.9% sCR Among evaluable pts (n=23): All maintained MRD-negative ≥12 months No relapses to date Median PFS, OS, DOR → not reached

Safety

Most AEs related to lymphodepletion: • Grade ≥3 neutropenia 88.9% • Lymphopenia 100% Infections in 31.2% (≥G3 in 18.8%) Hypogammaglobulinemia 44.4% (often improved with reduced IVIG) CRS: 52.8% (all G1–2), median onset 2 days ICANS: 2 cases (G1)

CAR-T Kinetics

• Median Cmax: 56,742 copies/µg gDNA
• Median T-max: 11 days
• AUC₀₋₂₈: 605,180

Title: BCMA CAR T-cell therapy in newly diagnosed transplant-ineligible multiple myeloma: An open label, single-arm, phase 2 study (CAREMM-001)

5th ASH abstract in myeloma

This one must make the list!!

Promising new real-world data from China !

Equecabtagene autoleucel (eque-cel) after ASCT shows strong safety & efficacy in ultra–high-risk multiple myeloma (UHR-MM) patients.

Why it matters:

UHR-MM patients still face poor outcomes despite advances in MM therapy. New strategies are urgently needed. Eque-cel, a BCMA-CAR-T therapy, is being explored earlier in treatment.

Study design:

• Retrospective review of 12 UHR-MM patients treated with ASCT ➜ eque-cel (Day 2–4). UHR defined by:
• High-risk cytogenetics (del17p ≥60%, TP53, t(4;14), etc.)
• Primary refractory disease
• Early relapse
• Primary PCL history

Who were the patients?

• Median age: 53
• 92% male
• 73% had genetic UHR features
• 17% had extramedullary disease
• Median prior lines: 2
• Most previously received daratumumab-based therapies

Treatment details: 

• ASCT conditioning primarily melphalan
• Eque-cel infused at 1×10⁶ cells/kg
• Robust CAR-T expansion: median Tmax 11 days, median Cmax 665 cells/µL

Safety: 

• CRS: Grade 1 (58%), Grade 2 (25%) — all recovered
• No ICANS
• Expected hematologic toxicities
• 100% hematopoietic recovery within ~1 month

Efficacy (as of July 1, 2025):

ORR 100% CR 100% All patients MRD-negative Median DOR, PFS & OS not yet reached Only 1 early-progression patient relapsed (Day 55)

Notable case:

Two pts had eque-cel before ASCT with only VGPR → After ASCT + second eque-cel: Achieved sCR & MRD-negativity As early as Day 23 post-ASCT in one case!

Conclusion:

Eque-cel after ASCT delivers deep, rapid & durable responses with a manageable safety profile in UHR-MM. A promising strategy deserving further clinical exploration.

Title: Promising safety and efficacy of equecabtagene autoleucel (eque-cel) followed ASCT in ultra high-risk multiple Myeloma (UHR-MM) patients: primary real world data from a single center

6th Abstract from ASH25 

Early data from the phase 1b MagnetisMM-30 trial show that combining elranatamab (ELRA) + iberdomide (IBER) delivers promising efficacy with a manageable safety profile in relapsed/refractory multiple myeloma (RRMM).

Why this matters

ELRA is a BCMA×CD3 bispecific with deep responses in prior trials. IBER is a next-gen CELMoD with enhanced immunomodulatory & antimyeloma activity. Together, they may offer a potent, fully off-the-shelf combination for RRMM

Study design:

MagnetisMM-30 (Part 1) • Phase 1b, open-label, dose-escalation • RRMM patients (2–4 prior lines, IMiD + PI exposed; no prior BCMA or CELMoD) • ELRA step-up dosing + QW or Q2W schedule • IBER: 0.75–1.3 mg D1-21 each cycle

Who were the patients? (n=22) 

• Median age: 68
• High-risk cytogenetics: 40.9%
• Extramedullary disease: 18%
• Triple-class refractory: 50% This is a tough-to-treat RRMM population.

Safety

• DLTs in 4 pts (G3 anorexia; G3 febrile neutropenia; G4 neutropenia ×2)
• TEAEs in 100% (G3/4: 68%) Most common:
• CRS 68% (all ≤G2) • Fatigue 64% • Neutropenia 59% (G3/4: 59%)
• Diarrhea 46%
• Anemia 32%
• Infections: 41% (G3/4: 5%)
• ICANS: 9% (G1–2)

Efficacy (preliminary)

• At 6.1-month median follow-up:
• Unconfirmed ORR: 90.9%
• CR or better: 45.5%
• VGPR+: 68.2%
• Confirmed ORR: 77.3%
• Median time to response: 1.1 months These are high response rates in early-phase RRMM combination testing.

Treatment exposure Median ELRA duration: 

• 3.1 mo overall
• 6.1 mo in DL1 ELRA + IBER still ongoing in 77% of patients at data cutoff.

Conclusion The ELRA + IBER combination shows:

• Favorable safety
• Rapid, deep, and high response rates
• Manageable CRS and cytopenias Enrollment and dose optimization continue, with longer follow-up to come.

Title : Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: Results from the phase 1b MagnetisMM-30 trial

7th Abstract from ASH25

Phase 2 IMMUNOPLANT Study Update! Exploring abbreviated, fixed-duration (4 cycles) linvoseltamab (Linvo) immuno-consolidation to deepen responses in newly diagnosed multiple myeloma patients who remain MRD-positive after triplet/quad therapy. A study from USA

Why this matters: Even with modern quadruplet regimens (PI + IMiD + anti-CD38), about 50% of NDMM patients stay MRD-positive. Linvoseltamab (a CD3xBCMA bispecific) may push responses deeper — without HDM-ASCT for those who defer it

Study design:

Single-center Phase 2 Up to 25 evaluable NDMM pts Must have VGPR+ but MRD-positive by clonoSEQ Receive 4–6 cycles of Linvo (step-up dosing) Primary goal: MRD conversion Secondary goals: sustained MRD-negativity, PFS, OS, safety

Treatment schedule: 

• Step-up doses: 5mg → 25mg → 200mg (C1–C3 weekly) • C4+: every 2 weeks
• MRD check after C4
• If still +, give C5–C6
• Afterwards → maintenance (typically lenalidomide)

Prophylaxis:

• Tocilizumab pre-dose to prevent CRS
• Dexamethasone C1
• Standard antimicrobials, IViG, VTE prophylaxis

Results (as of July 23, 2025):

19 enrolled (median age 60). Therapy history: KRd, D-VRd, D-KRd, DRd, Isa-VRd. All patients MRD-positive at entry.

Big headline:

Among the 14 who completed 4 cycles & had MRD assessed… 100% achieved MRD negativity by both:

• NGS clonoSEQ (10⁻⁶)
• Flow cytometry (10⁻⁵) (13 sCR, 1 VGPR) No relapses so far.

Safety:

• No CRS
• No ICANS

Most AEs were mild (URI, rash, cough, bone pain, neutropenia). Only two grade 3 events; no grade 4/5 AEs.

Conclusion:

Short-course Linvo immuno-consolidation shows exceptional MRD-negative rates (100% so far) in NDMM patients still MRD-positive after modern combos. The study moves into Part 2 (target: 50 pts). More data coming at the Meeting!

Title: A phase 2 trial of abbreviated fixed-duration (Default 4 Cycles) linvoseltamab immuno-consolidation to deepen responses post newly diagnosed multiple myeloma combination therapy for minimal residual disease positivity (the IMMUNOPLANT Study)

Abstract 8th: ASH25

New data alert in Multiple Myeloma!

Interim results from the Phase III COBRA trial compare KRd (carfilzomib/lenalidomide/dex) versus VRd (bortezomib/lenalidomide/dex) in newly diagnosed MM (NDMM).

Why it matters: VRd is the current frontline standard. KRd has shown strong activity, but previous head-to-heads (e.g., ENDURANCE) didn’t show PFS benefit. COBRA revisits this across all NDMM patients, regardless of transplant eligibility or cytogenetics.

Study design: 250 patients randomized 1:1 to KRd versus VRd.Co-primary endpoints:

• MRD-negative CR at 12 months
• Progression-free survival (PFS) Both were met at interim analysis.

MRD results: At 10⁻⁵ sensitivity:

• KRd: 31%
• VRd: 18%

At 10⁻⁶ sensitivity:

• KRd: 19%
• VRd: 7% KRd significantly improves depth of response.

Progression-free survival: KRd significantly prolonged PFS versus VRd.

• Median PFS: Not reached (KRd) versus 49 months (VRd)
• HR = 0.57 (p = 0.0095) A notable PFS advantage not seen in ENDURANCE.

Other efficacy findings:

• ORR high in both arms: 94% KRd versus 91% VRd
• CR or better: 71% KRd versus 53% VRd

Clear improvement in depth of response with KRd.

Safety:

• Grade ≥3 AEs: 72% KRd versus 62% VRd
• Neutropenia ≥3: 21% KRd versus 11% VRd
• Peripheral neuropathy (any grade): 17% KRd versus 56% VRd
• Cardiac events (any grade): 18% KRd versus 10% VRd

Two KRd treatment-related deaths reported.

Takeaway: COBRA demonstrates superior efficacy of KRd over VRd in frontline NDMM, including MRD-negativity and PFS—with expected, manageable toxicity profiles. Supports further evaluation of KRd-based induction strategies.

Abstract Number: abs25-10191.”

Title: Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) – interim results from the randomized Phase III COBRA trial.

Abstract 9th from ASH25;

From the world

Abstract abs25-7875 Updated efficacy & safety data for JNJ-5322, a next-gen BCMA × GPRC5D × CD3 trispecific antibody for relapsed/refractory multiple myeloma (RRMM)!

What is JNJ-5322?

A novel trispecific antibody targeting BCMA + GPRC5D + CD3 — designed to improve binding, overcome clonal heterogeneity, & reduce antigen escape. Built for deep, durable responses.

Study population

• (RP2D cohort, n=36)
• Median follow-up: 14.4 mo
• Median prior lines: 4
• 75% BCMA/GPRC5D-naive
• 52.8% triple-class refractory
• High-risk cytogenetics: 26.5%

Safety 

• Common TEAEs: infections (80.6%), skin (66.7%), nails (61.1%)
• Cytopenias: lymphopenia (47.2%), neutropenia (44.4%)
• CRS: 52.8% (mostly grade 1)
• No ICANS observed
• Taste changes in 58.3% (median 57 days)

IVIg use was recommended to keep Ig ≥400 mg/dL 

• 91.7% received IVIg
• Hypogammaglobulinemia in 52.8%

Efficacy in BCMA/GPRC5D-naive (n=27)

• ORR: 100%
• ≥CR: 77.8%
• 12-mo PFS: 96.3%
• MRD-negativity (10⁻⁵): 100% (10/10) Durable, deep responses with continued improvement

Only 1 death (pneumonia in the setting of Ig <200 mg/dL). All remaining pts in ongoing response at 15-mo median follow-up.

Conclusion

JNJ-5322 shows CAR-T-like response rates with off-the-shelf convenience, Q4W dosing, and low grade ≥2 CRS — a promising approach for dual-antigen myeloma targeting. More data coming!

Title: Updated efficacy and safety results of JNJ-5322, a novel, next-generation BCMA×GPRC5D×CD3 trispecific antibody, in patients with Relapsed/Refractory multiple myeloma

Finally I found the 10th abstract for ASH25

Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of DPd/DVd in Pts with RRMM: majestec-3

Practice-changing data in RRMM! MajesTEC-3 is the first phase 3 trial of a BCMA×CD3 bispecific in MM, comparing Teclistamab + Daratumumab (Tec-Dara) vs DPd/DVd in pts with 1–3 prior lines. Results: Profound PFS & OS benefit with Tec-Dara.

Why this matters:

In RRMM, attrition rises & response durability falls with each LOT. Early introduction of effective immunotherapies is crucial. Dara creates an immune-permissive microenvironment → synergistic with Tec’s T-cell redirection.

Population:

587 pts, median age 64 (range 25–88), median 2 prior LOTs. Included: len-refractory, high-risk cytogenetics, soft-tissue plasmacytomas, prior anti-CD38 exposure. Excluded: anti-CD38–refractory, prior BCMA-therapy.

Primary Endpoint:

PFS Tec-Dara reduced risk of progression/death by 83% vs DPd/DVd. HR 0.17 (95% CI 0.12–0.23, P<0.0001) mPFS: NR vs 18.1 mo 36-mo PFS: 83.4% vs 29.7%

Consistent across ALL prespecified subgroups—including ≥75 yrs & high-risk disease.

Depth of response:

Tec-Dara delivered substantially higher response quality. ≥CR: 81.8% vs 32.1% ORR: 89.0% vs 75.3% MRD-neg (10⁻⁵): 58.4% vs 17.1% These are benchmark-level results for early-relapse RRMM

Overall Survival:

Tec-Dara significantly improved OS. HR 0.46 (95% CI 0.32–0.65; P<0.0001) 36-mo OS: 83.3% vs 65.0%

90% of pts alive at 6 months lived to 30 months

Treatment exposure:

Pts stayed on Tec-Dara much longer:

• Median tx duration: 32.4 vs 16.1 mo
• 71% on therapy at cutoff vs 28.3% (DPd/DVd).

Safety:

Overall grade 3/4 & grade 5 TEAEs similar across arms. CRS: 60.1% (mostly grade 1/2) ICANS: 1.1% Infections higher with Tec-Dara (96.5% any grade; 54.1% grade 3/4) but decreased over time with Q4W dosing + Ig & antimicrobial prophylaxis. Discontinuation due to AEs stayed low (4.6%)

Conclusion:

Tec-Dara demonstrates clinically remarkable, statistically robust improvements in PFS, OS, MRD, and depth of response. With 83% of pts PFS-alive at 3 yrs, this off-the-shelf immunotherapy is poised to become a new standard of care at first relapse.”

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