🔬🩸 Hematology Updates: Functional Cure Signals, Head-to-Head CAR-T, Outpatient Bispecifics, BTK Approval, and More
From five-year MRD-negative remissions in myeloma to Lyell’s Phase 3 CAR-T, outpatient epcoritamab, Singapore’s orelabrutinib approval, and key AML and thalassemia milestones—this week showcases meaningful advances across blood cancers and rare diseases.
In Today’s Newsletter
🧪 Inobrodib + BCMA bispecifics start dosing in RRMM (CellCentric) [1] [03 Sep 2025]
https://firstwordpharma.com/story/5994455
Context: First-in-class oral p300/CBP inhibitor; ongoing Phase 1/2 in R/R MM; ~40 pts planned across combos.
Key point: New cohorts initiated combining inobrodib with teclistamab or elranatamab; initial safety readout targeted by end-2025 (endpoint specifics not stated).
Implication: Signals pipeline investment and modality expansion.
💉 Cilta-cel at SOHO: 5-yr CR/MRD-neg patients off maintenance 🟢 [2] [07 Sep 2025]
https://www.cancernetwork.com/view/after-5-years-of-no-cr-mrd-with-cilta-cel-no-maintenance-required
Context: CARTITUDE-1 (phase 1b/2) in heavily pretreated R/R MM; investigator interview.
Key point: One-third PFS at ~5 years; 12 pts with annual MRD/PET-CT negativity for 5 years reported as not needing maintenance; “cure” suggested by investigator (interpret cautiously).
Implication: May influence prescriber choice and payer reviews pending full data.
🧬 Lyell starts Phase 3 H2H: ronde-cel vs CD19 CAR-Ts in 2L LBCL [3] [US • 03 Sep 2025]
Context: PiNACLE-H2H to randomize ~400 pts to ronde-cel vs liso-cel/axi-cel; primary endpoint EFS.
Key point: Dual-target CD19/CD20 CAR-T (ronde-cel; RMAT + Fast Track) moves into first-of-its-kind head-to-head trial; outpatient option included per safety to date.
Implication: Signals pipeline investment and modality expansion.
🏥 Epcoritamab outpatient feasibility in R/R DLBCL (EPCORE NHL-6) [4] [EU • 03 Sep 2025]
Context: Phase 2, n=92; US community + academic sites; subcutaneous CD3xCD20 bispecific.
Key point: 92% received first full 48-mg dose outpatient; CRS mostly grade 1–2; after one prior line (n=42), ORR 64.3% and CR 47.6% at 5.8-mo median follow-up.
Implication: May expand screening, initiation, and follow-up at scale.
🌏 Orelabrutinib approved for R/R MZL in Singapore (InnoCare) [5] [Singapore • 08 Sep 2025]
Context: Highly selective BTK inhibitor; second indication in Singapore.
Key point: HSA approval for adult R/R MZL broadens regional access; company cites efficacy/safety profile (metrics not specified).
Implication: Introduces competition that may affect pricing and formulary access.
🧠CX-5461 (pidnarulex) IND cleared for MYC-driven B-cell lymphomas (Senhwa) [6] [05 Sep 2025]
https://www.senhwabio.com/en/news/20250905
Context: First-in-class G-quadruplex stabilizer; prior signals in lymphoma via PMCC (Australia).
Key point: FDA cleared Phase 1b/2 in MYC-aberrant B-cell lymphoma subtypes; company highlights cross-cancer potential (study details not fully specified).
Implication: Signals pipeline investment and modality expansion.
⚡ CER-1236 gets FDA Fast Track in AML (CERo Therapeutics) [7] [US • 05 Sep 2025]
Context: Adds to Orphan Drug status; first-in-human Phase 1/1b ongoing (R/R AML, MRD-positive, TP53-mut MDS/AML).
Key point: Fast Track enables enhanced FDA interactions and rolling review; platform uses chimeric engulfment receptor T cells (CER-T).
Implication: Signals pipeline investment and modality expansion.
🏫 BBCI AML conference focuses on diagnostics, MRD, access (India) [8] [India • 05 Sep 2025]
https://vohnetwork.com/news/policy/bbci-hosts-conference-on-advances-in-acute-myeloid-leukemia-care
Context: One-day meeting in Guwahati with national centers; 90+ postgraduates.
Key point: Sessions covered risk stratification, flow/NGS, MRD, novel agents, transplant, supportive care; emphasis on earlier referral and equitable transplant access.
Implication: May expand screening, initiation, and follow-up at scale.
🩸 PYRUKYND (mitapivat) thalassemia sNDA PDUFA extended to Dec 7, 2025 (Agios) [9] [US • 04 Sep 2025]
https://investor.agios.com/news-releases/news-release-details/agios-provides-update-us-pdufa-goal-date-pyrukyndr-mitapivat
Context: FDA requested REMS proposal addressing hepatocellular injury risk; ENERGIZE/ENERGIZE-T support the filing.
Key point: 3-month extension; no new efficacy/safety data requested; current US indication is PK deficiency (not thalassemia).
Implication: Introduces competition that may affect pricing and formulary access.
🧒 ACCRUFeR/FeRACCRU (ferric maltol) gets US Priority Review in adolescents with IDA (Shield) [10] [UK • 04 Sep 2025]
Context: Clinical Supplement filed June 2025; based on FORTIS/ST10-01-305 Phase 3 pediatric data.
Key point: FDA Priority Review to extend label to ≥10 years; EU submission by Norgine also filed; broader 1-month+ suspension NDA planned.
Implication: Introduces competition that may affect pricing and formulary access.
Why it matters
Outpatient bispecific dosing (epcoritamab) could relieve inpatient bottlenecks and widen community access [4].
First H2H CAR-T trial in LBCL sets a new evidentiary bar for dual-target designs vs approved CD19 products [3].
Regional BTK expansion (orelabrutinib) underscores Asia-Pacific lymphoma market dynamism [5].
Early-phase pushes on MYC targeting and novel T-cell constructs diversify lymphoma/AML modalities [6][7].
Pediatric ID/IDA and thalassemia filings show steady movement on non-malignant hematology access [9][10].
📢 Stay Ahead in Hematology!
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FAQ
What exactly did CellCentric kick off in myeloma?
Initiated dosing of inobrodib with teclistamab or elranatamab in a Phase 1/2 R/R MM study (~40 pts across combos); early safety readout aimed by end-2025 [1].
Is cilta-cel now considered a “cure” for some patients?
An investigator at SOHO reported CARTITUDE-1 5-year outcomes with a subset MRD/PET-CT-neg for 5 years without maintenance and described this as “cure”; it’s a phase 1b/2 context, so interpret cautiously [2].
What does Lyell’s Phase 3 compare?
Ronde-cel (dual CD19/CD20) vs investigator’s choice liso-cel or axi-cel in 2L LBCL; primary endpoint event-free survival; ~400 pts planned [3].
How “outpatient” is epcoritamab in NHL-6?
92% received the first full 48-mg dose as outpatients; CRS largely grade 1–2; in 1-prior-line pts, ORR 64% with 47.6% CR at ~5.8 months median follow-up [4].
Where is orelabrutinib newly approved, and for what?
Singapore HSA approved Innochem (orelabrutinib) for adult R/R marginal zone lymphoma; second indication there [5].
What changed for PYRUKYND’s thalassemia review?
FDA extended the PDUFA goal date to 07 Dec 2025 after a REMS submission; no new efficacy/safety data were requested [9].
Entities / Keywords
CellCentric; inobrodib (p300/CBP inhibitor) • Janssen/Legend; ciltacabtagene autoleucel (Carvykti; cilta-cel) • Lyell; rondecabtagene autoleucel (ronde-cel; LYL314) • Genmab/AbbVie; epcoritamab (EPKINLY/TEPKINLY) • InnoCare; orelabrutinib (Innochem/HIBRUKA) • Senhwa; pidnarulex (CX-5461) • CERo; CER-1236 (CER-T) • Agios; PYRUKYND (mitapivat) • Shield/Norgine; ferric maltol (ACCRUFeR/FeRACCRU) • LBCL, DLBCL, MZL, AML, MM, thalassemia, IDA.
References
https://firstwordpharma.com/story/5994455
https://www.cancernetwork.com/view/after-5-years-of-no-cr-mrd-with-cilta-cel-no-maintenance-required
https://www.senhwabio.com/en/news/20250905
https://vohnetwork.com/news/policy/bbci-hosts-conference-on-advances-in-acute-myeloid-leukemia-care