The throughline of 2025 was not a single modality—it was the convergence of deep response signals (often tracked by MRD), multi-region regulatory momentum, and more explicit proof points on deliverability for complex therapies.
Dive deeper
The year’s storyline: Three Consistent Shifts Shaping Hematology in 2025
Hematology’s 2025 updates clustered around three consistent shifts.
MRD Negativity in Frontline Multiple Myeloma: Depth of Response as a Marker of Durable Benefit
Regulators and payers increasingly framed sustained (minimal/measurable residual disease), negativity as a marker of durable benefit in communications around frontline myeloma regimens
Fixed-Duration Regimens in Hematology 2025: Policy Momentum Led by CLL
In CLL, fixed-duration oral combinations moved beyond “preferred strategy” into concrete regional action, including European Union clearance and CHMP support for approval.
Hematology 2025: Delivery and Execution Become Measurable Endpoints
Outpatient feasibility, manufacturing cycle times, and safety syndromes such as CRS (cytokine release syndrome) and ICANS (immune effector cell–associated neurotoxicity syndrome) were repeatedly reported as quantifiable variables that shape real-world execution for bispecifics and CAR‑T as well as next‑generation antibodies
Practice-Shaping Clinical Readouts in Hematology That Defined 2025
Multiple Myeloma 2025: Frontline MRD Depth and Durable Outcomes in PERSEUS and CEPHEUS
Johnson & Johnson’s DARZALEX FASPRO (daratumumab) featured prominently in myeloma updates. In PERSEUS, newly diagnosed patients receiving D-VRd and D-R maintenance achieved ninety-five percent progression-free survival at four years, with fifty-six percent maintaining MRD negativity for over twenty-four months. In CEPHEUS, transplant-ineligible patients had sixty percent MRD negativity and sixty-nine percent progression-free survival at fifty-four months.
Multiple Myeloma in 2025: Trispecific Antibody Momentum and Regulatory Designation (ISB 2001)
IGI’s trispecific antibody ISB 2001 (BCMA/CD38/CD3) reported an overall response rate of seventy-nine percent, with thirty percent complete or stringent complete responses, and CRS described as predominantly Grade 1. The program also received FDA Fast Track Designation.
These data emerged against an already crowded BCMA/bispecific backdrop, suggesting trispecific constructs may find room for incremental depth with manageable low‑grade CRS
Diffuse Large B-Cell Lymphoma in 2025: Five-Year POLARIX Outcomes
Long-term POLARIX results continued to be emphasized for frontline diffuse large B-cell lymphoma. At five years, progression-free survival was sixty-four point nine percent for Polatuzumab-R-CHP versus fifty-nine point one percent for R-CHOP, while overall survival was eighty-two point three percent versus seventy-nine point five percent, respectively.
CLL: fixed-duration oral therapy in Europe (AMPLIFY; EU approval and CHMP recommendation)
A fixed-duration, all-oral combination of Calquence (acalabrutinib) + venetoclax, with or without obinutuzumab, received European Union approval for frontline CLL. In AMPLIFY, the regimen showed three-year progression-free survival rates of seventy-seven to eighty-three percent and reduced the risk of progression or death by up to fifty-eight percent versus chemoimmunotherapy. Separately, the EMA’s CHMP recommended approval for this combination in previously untreated patients.
Follicular lymphoma: first FDA-approved bispecific antibody combination in lymphoma (EPCORE FL-1)
AbbVie announced FDA approval of EPKINLY (epcoritamab-bysp) plus rituximab and lenalidomide (R2) for adults with relapsed/refractory follicular lymphoma after at least one prior systemic therapy. In Phase 3 EPCORE FL-1, epcoritamab + R2 reduced risk of progression or death by seventy-nine percent versus R2 alone (hazard ratio 0.21). Overall response was eighty-nine percent versus seventy-four percent, and complete response was seventy-four percent versus forty-three percent. CRS occurred in twenty-four percent (mostly grade 1–2), and one grade 1 ICANS event was reported.
This represented the first FDA-approved bispecific antibody combination regimen in lymphoma, establishing an outpatient‑feasible, fixed‑duration option beyond CAR‑T
Delivery proof point: outpatient feasibility for epcoritamab in DLBCL
Epcoritamab was also described as outpatient-feasible in relapsed/refractory DLBCL: ninety-two percent received the first full forty-eight milligram subcutaneous dose as outpatients; CRS was Grade 1–2 only; ICANS occurred in seven point six percent, was low-grade, and resolved.
CAR-T in myeloma: long-term durability and the impact of bridging response (CARTITUDE-1; CARTITUDE-4)
For cilta-cel, CARTITUDE-1 was summarized as follows: thirty-two of thirty-seven patients were alive and progression-free at or beyond five years after a single infusion; twelve sustained complete response, remained MRD-negative and PET/CT-negative for five years, and required no maintenance; median overall survival reached sixty point seven months in a heavily pretreated population.
Separately, CARTITUDE-4 bridging-response analysis linked depth of response to outcomes and safety signals. Patients achieving at least partial response (≥PR) with bridging had better outcomes and fewer fatal adverse events than those with <PR. VGPR+ bridging responders were reported to have approximately seventy-six percent progression-free survival and eighty-five percent overall survival at thirty months, with lower infections, less prolonged cytopenias, and no delayed Parkinson-like neurotoxicity reported in that subgroup.
These findings intersect with evolving safety expectations and REMS updates for cilta‑cel, underscoring that depth and durability must be balanced with neurotoxicity and infection vigilance in real‑world use
Ultra-fast manufacturing: UF-Kure19 in relapsed/refractory non-Hodgkin lymphoma
UF-Kure19 CAR-T was described as achieving eighty percent complete response in a recent trial, while reducing manufacturing to less than one day. CRS occurred in twenty percent and neurotoxicity in ten percent, with both resolving within 24 hours.
Sub‑24‑hour manufacturing was positioned as a way to reduce wait‑list attrition and intensive‑care utilization, directly linking cycle time to capacity and access
Key Hematology Approvals, Guidelines, and Access Decisions in 2025
Hematology in the United States 2025: FDA Actions and Clinical Guidance
KOMZIFTI (ziftomenib) was added to the NCCN AML Guidelines as a Category 2A option for adults with relapsed/refractory NPM1-mutated AML, following FDA approval on 13 Nov 2025 supported by KOMET-001 (CR/CRh twenty-one point four percent, median duration five months). The label carries a boxed warning for differentiation syndrome. The NPM1‑mut focus underlined the continued shift toward biomarker‑defined AML niches
Other U.S. actions described during the year included AbbVie’s FDA approval announcement for EPKINLY in follicular lymphoma and Grifols’ FDA pediatric label expansion for THROMBATE III.
In thalassemia, the FDA extended the PDUFA date for PYRUKYND (mitapivat) to December 7, 2025, following submission of a REMS to mitigate hepatocellular injury (no new efficacy or safety data were requested).
EU Hematology 2025: Approvals and CHMP Recommendations
ADCETRIS + BrECADD was approved in the EU for previously untreated advanced Hodgkin lymphoma, based on HD21 safety framing and non-inferior progression-free survival versus historical eBEACOPP.
Bristol Myers Squibb received European Commission approval expanding Breyanzi (lisocabtagene maraleucel) to adult relapsed/refractory mantle cell lymphoma after at least two lines including a BTK inhibitor, citing TRANSCEND MCL outcomes.
The European Commission also approved Regeneron’s Lynozyfic (BCMAxCD3 bispecific) for relapsed/refractory multiple myeloma after at least three prior therapies; results cited included a seventy-one percent overall response rate and fifty percent complete response or better in LINKER-MM1, along with response-adapted dosing every four weeks following response onset.
England and Wales 2025: NICE and NHS Commissioning Decisions in Hematology
NICE recommended AUCATZYL (obe-cel) for routine NHS commissioning in England and Wales for adults aged 26 and older with relapsed/refractory B-cell precursor acute lymphoblastic leukemia, following MHRA conditional authorization in April 2025.
Global Hematology 2025: Regulatory and Access Updates From Canada, Japan, Germany, Austria, Spain, and Singapore
In Canada, the Canadian Drug Agency recommended conditional public reimbursement for belantamab mafodotin combination regimens (BPd and BVd) for relapsed/refractory multiple myeloma, following Health Canada’s July 2025 approval and urging progression to pCPA negotiations.
In Japan, Chugai and Nippon Shinyaku updated the electronic package insert for Gazyva (obinutuzumab) enabling use with venetoclax for previously untreated CD20-positive CLL and SLL, referencing Phase II M20-353 in Japan and global Phase III CLL14.
In Germany, the Paul Ehrlich Institut granted first approval for Prufibry (fibrinogen concentrate) across age groups; Austria and Spain were expected to follow via decentralized procedure, while U.S. BLA review was ongoing with a decision anticipated by year end. As a fibrinogen concentrate, Prufibry also contributed to the supportive‑care infrastructure underpinning complex hematologic and oncologic procedures.
In Singapore, orelabrutinib was approved for relapsed/refractory marginal zone lymphoma (its second indication in the country).
Safety and Delivery Considerations Shaping Hematology Practice in 2025
Several 2025 updates paired efficacy with practical safety framing.
For bispecific combinations and T-cell redirection, CRS and ICANS were repeatedly reported with event rates and severity. In EPCORE FL-1, CRS occurred in twenty-four percent (mostly grade 1–2) with one grade 1 ICANS event reported. In DLBCL, epcoritamab outpatient feasibility was described alongside CRS limited to Grade 1–2 and ICANS at seven point six percent (low-grade, resolved).
For targeted AML, the ziftomenib label’s boxed warning for differentiation syndrome was highlighted alongside FDA approval and NCCN guideline placement.
For CAR-T, measurable links were reported between disease control during bridging and downstream safety-relevant outcomes such as infections and prolonged cytopenias (CARTITUDE-4 analysis).
MRD and Diagnostics in Hematology 2025: How Measurement Informed Clinical Decisions
MRD was presented as both a response-depth marker and an outcome-linked variable.
In newly diagnosed myeloma, PERSEUS and CEPHEUS linked MRD negativity to longer-horizon endpoints, and in CARTITUDE-1, a subset of long-term responders were described as remaining MRD-negative and PET/CT-negative for five years. Taken together, these programs positioned sustained MRD negativity as a potential surrogate that future trials and guideline panels may leverage more formally.
MRD also appeared in transplant-adjacent care. In the Phase 2 EndRAD trial across 45 North American centers, pediatric/AYA B-ALL patients who were NGS-MRD negative in CR1/CR2 before allogeneic HCT received non-TBI conditioning; reported outcomes included two-year EFS of seventy-six point three percent and OS of eighty-two point zero percent, with post-HCT NGS-MRD positivity predicting worse outcomes. EndRAD illustrated how MRD status can influence not only prognosis but also conditioning intensity and modality choices in transplant pathways.
In AML, Ingenium Therapeutics’ Gengleucel was cleared to proceed directly to Phase 2 in MRD-positive AML, using MRD-negativity as a primary endpoint; prior treatment experience in South Korea and planned U.S. trial initiation in early 2026 were also noted. However, the real‑world impact of MRD‑driven strategies will hinge on reliable NGS/MRD testing availability and reimbursement beyond major academic centers.
Catalyst calendar (timelines explicitly flagged during the year)
Late 2025: Near-Term Hematology Clinical Catalysts
- Halia Therapeutics: HT-6184 low-risk MDS topline results expected by late 2025.
- CellCentric: initial safety readout expected by end of 2025 for inobrodib + BCMA bispecific combinations (teclistamab or elranatamab); separate Phase 2 dose-optimization data for inobrodib + pomalidomide/dexamethasone expected in late 2025.
- Moleculin Biotech: MIRACLE Phase 3 trial results expected later in the year (adult context referenced).
October–December 2025: Regulatory Milestones
- FDA PDUFA date for PYRUKYND (mitapivat) in thalassemia extended to December 7, 2025.
Early 2026: Trial Initiations and Program Advancements
- Lyell: enrollment expected to begin by early 2026 for Phase 3 ronde-cel head-to-head trial in second-line large B-cell lymphoma (outpatient option included).
- Ingenium: Phase 2 trial in MRD-positive AML set to begin in U.S. centers in early 2026.
Q2 2026: First-in-Human Programs
- CHARM Therapeutics: first-in-human evaluation targeted for Q2 2026 for CHM-029 (pan-menin inhibitor).
What These Catalysts Signal for Hematology
Collectively, these milestones will test whether 2025’s themes—MRD‑anchored depth, outpatient T‑cell redirection, and ultra‑fast manufacturing—translate into broader indications and earlier‑line use.
Key Hematology Takeaways for 2025
Hematology in 2025 combined higher response-depth and durability signals in major malignancies (often including MRD), a dense set of approvals and access decisions across the United States, European Union, and multiple individual countries, and more explicit reporting of delivery variables—outpatient feasibility, manufacturing cycle time, and safety syndromes that shape how therapies are deployed in practice.
As safety frameworks, HTA decisions, and diagnostic access catch up, competitive advantage in 2026–2027 will sit at the intersection of depth of response, access economics, and deliverability at scale
🚀 Accelerate your success. Contact us now
📂 Explore our case studies. See examples of our work.
💡 Read our insights. Learn from our latest reports and analysis
🎬 Watch on YouTube. Subscribe and never miss a video.
🧰 See our full range of services. Discover how we can help you.
📚 View the full Hematology archive on our research hub page.