NegativePractice-confirming
PASHA · AML
Gilteritinib vs midostaurin in newly diagnosed FLT3-mutated AML. OS was not improved (HR 1.02, P=0.864). Midostaurin plus intensive chemotherapy remains standard of care.
CPD working notes from the EHA Congress, Stockholm, June 11 to 14, 2026
Fact-checked clinical education notes distilled into practical haematology take-home messages. Every figure below is drawn from the EHA 2026 Congress working notes; where evidence is preliminary, early phase, or not yet practice-changing, this is stated plainly.
The fastest read for a busy consultant. Impact tags are an MHA teaching judgement, not a guideline statement.
Fixed-duration pirtobrutinib plus venetoclax-rituximab cut progression or death by 45% (PFS HR 0.547) with deeper MRD; pirtobrutinib is already licensed after a covalent BTK inhibitor.
Tafasitamab-lenalidomide-R-CHOP improved PFS (HR 0.75) in high-risk disease. Overall survival is not yet mature, so adoption should wait for OS and health-economic data.
INCA033989 produced clinical and molecular responses across MF and ET (87% haematologic response, 70% complete in ET). Still phase 1, but with Breakthrough Therapy Designation.
Nipocalimab gave a durable haemoglobin response roughly three times placebo in the first randomised wAIHA trial. The filing already holds FDA Priority Review.
LB2501 (in vivo CD19/CD20) reached infusion in a median of 17.5 days with no ICANS; REVSTAR-123 brings a switchable allogeneic CD123 product to AML. Both are early phase 1.
Where each signal sits on the path from current practice to the future, based only on what was reported.
PASHA was negative for overall survival, and ATG stays standard for unrelated-donor transplant. EPO remains first-line for lower-risk MDS anaemia.
BRUIN CLL-322 supports pirtobrutinib combinations; the drug is already licensed after a covalent BTK inhibitor. Awaiting overall survival.
frontMIND supports a frontline DLBCL submission; nipocalimab for wAIHA holds FDA Priority Review; the ropeginterferon ET decision is due 30 August 2026; mezigdomide submissions are expected.
INCA033989 has a planned phase 3 in CALR-mutant ET; mezigdomide builds on the SUCCESSOR programme in relapsed myeloma.
In vivo CAR-T (LB2501) and off-the-shelf allogeneic CD123 CAR-T (REVSTAR-123) are phase 1 today, plausibly 5 to 10 years from routine use if validated.
This page was checked against EHA 2026 congress press releases and haematology news coverage (company releases, OncLive, AJMC and similar). Trial names, abstract numbers, presenters and most headline statistics verified accurately. The following corrections were applied; the original EHA Library abstracts remain the definitive source.
Six headline readouts from the congress, kept concise and evidence-balanced. Badges indicate the nature of each result rather than a recommendation.
Gilteritinib vs midostaurin in newly diagnosed FLT3-mutated AML. OS was not improved (HR 1.02, P=0.864). Midostaurin plus intensive chemotherapy remains standard of care.
Selinexor plus ruxolitinib. Spleen response was improved (SVR35 49.8% vs 28.0%, P<0.0001) but symptom score was not (TSS P=0.825).
Pirtobrutinib plus venetoclax-rituximab cut progression or death risk by 45% (PFS HR 0.547, P=0.0001) and improved deep undetectable MRD at 10⁻⁶ (52.1% vs 35.0%) at end of treatment.
Mezigdomide plus carfilzomib-dexamethasone (MeziKd) improved PFS in RRMM (18.0 vs 8.3 months, HR 0.48, P<0.0001). Mezigdomide is not yet approved.
Tafasitamab-lenalidomide-R-CHOP improved PFS over R-CHOP (HR 0.75, P=0.019) in high-risk frontline DLBCL. OS data are not yet mature.
Nipocalimab (anti-FcRn) produced a durable haemoglobin response signal in warm AIHA (24% vs 8% placebo, P=0.015). First targeted randomised data in this condition.
An at-a-glance verdict for every trial. The impact score and verdict are an MHA teaching judgement to aid revision, not a guideline or a recommendation. Local policy, licensing, reimbursement and MDT discussion always govern practice.
| Trial | Practice impact | Monday morning? | Why |
|---|---|---|---|
| BRUIN CLL-322 CLL |
8/10 |
Probably yes | Strong PFS (HR 0.547) and deeper MRD; pirtobrutinib already licensed post-cBTKi. |
| frontMIND DLBCL |
7/10 |
Not yet | First frontline win over R-CHOP since rituximab, but OS immature and toxicity higher. |
| SUCCESSOR-2 Myeloma |
7/10 |
Not yet | PFS doubled (18 vs 8.3 mo), but mezigdomide is not yet approved. |
| Menin inhibitors AML |
6/10 |
Selected use | Revumenib and ziftomenib already approved in R/R disease; combinations remain investigational. |
| ImmunoPRISM Smouldering myeloma |
6/10 |
Investigational | Striking depth of response, but phase 2 in pre-malignant disease with real toxicity. |
| ENERGY Warm AIHA |
6/10 |
Not yet (filing) | First targeted randomised data; nipocalimab wAIHA application holds FDA Priority Review. |
| SENTRY Myelofibrosis |
5/10 |
Not yet | Spleen benefit and an early OS signal, but symptom endpoint not met. |
| RISE UP Sickle cell |
5/10 |
Not yet | Clear haemoglobin benefit, but the pain-crisis endpoint was not met. |
| INCA033989 MF / ET |
5/10 |
Watch | Promising clinical and molecular responses, but still phase 1. |
| SURPASS-ET Essential thrombocythaemia |
5/10 |
Watch | Ropeg approved for PV; ET under FDA review, decision due 30 August 2026. |
| MonumenTAL-3 Myeloma |
5/10 |
Watch | Talquetamab versus DPd; EHA 2026 efficacy figures not independently verified here. |
| ATG in MUD-HCT Transplant |
4/10 |
Confirms practice | Settles the question: ATG stays standard in unrelated-donor transplant. |
| INDEPENDENCE Myelofibrosis |
4/10 |
Watch | Luspatercept for MF anaemia on JAKi; specifics not independently verified here. |
| PASHA AML |
3/10 |
Confirms practice | Negative for OS; midostaurin plus chemotherapy remains standard. |
| EPO-PRETAR MDS |
3/10 |
Confirms practice | Reinforces EPO first-line for lower-risk MDS anaemia (item not independently verified). |
| REVSTAR-123 AML |
2/10 |
Early phase | Phase 1a off-the-shelf CD123 CAR-T; remissions reported, no GVHD or ICANS. |
| LB2501 B-cell NHL |
2/10 |
Early phase | First-in-human in vivo CAR-T; striking early responses but n=6 at the higher dose. |
| BCMA CAR-T (ITP) Autoimmune |
2/10 |
Proof of concept | 8 dosed, 4 evaluable, all in CR; landmark concept, not practice. |
| CD5 inhibition Cellular therapy concept |
1/10 |
Concept | Biological idea to boost bispecifics; awaiting trials (not independently verified). |
A negative frontline FLT3 readout that confirms current practice, alongside early-stage cellular therapy and ongoing menin inhibitor combinations.
First head-to-head phase 3 of a 2nd-generation FLT3 inhibitor (gilteritinib) vs a 1st-generation inhibitor (midostaurin), each with intensive chemotherapy, in newly diagnosed FLT3-mutated AML (ITD and TKD).
Interpretation: A clear negative primary result. Gilteritinib did not improve OS over midostaurin in the frontline intensive setting. The investigators attribute OS equivalence partly to frequent gilteritinib salvage after midostaurin progression and a higher rate of allogeneic transplant in the midostaurin arm. Secondary coverage confirmed longer event-free and relapse-free survival with gilteritinib but did not publish the exact medians, so the working-notes EFS figures of 51.1 vs 19.9 months (HR 0.83, P=0.052) should be treated as provisional pending the full abstract.
First-in-class switchable allogeneic (off-the-shelf) CAR-T targeting CD123 in relapsed/refractory AML. The switchable design allows external on/off control of CAR activity to limit on-target myelosuppression and cytokine release.
Why it matters: CD123 is broadly expressed on AML blasts and leukaemic stem cells. An allogeneic product avoids the 4 to 6 week manufacturing time that often makes autologous CAR-T impractical given AML kinetics.
Menin inhibitors target the menin-KMT2A interaction in NPM1-mutated and KMT2A-rearranged AML. Revumenib holds FDA accelerated approval (2023) for relapsed/refractory KMT2A-rearranged AML.
EHA 2026 combination data (menin inhibitor plus venetoclax plus azacitidine) showed deep responses in NPM1-mutated AML, including venetoclax-pre-exposed patients, suggesting menin inhibition may partly restore differentiation competency.
A split-endpoint myelofibrosis combination, an anaemia trap-ligand, and the arrival of mutation-specific CALR targeting.
Selinexor (oral XPO1 inhibitor) plus ruxolitinib vs ruxolitinib plus placebo in JAKi-naive myelofibrosis. Co-primary endpoints: SVR35 and absolute change in total symptom score (TSS, excluding fatigue) at week 24.
Interpretation: Spleen benefit is unambiguous and clinically meaningful (21.8% absolute SVR35 gain). Symptom control was not improved over ruxolitinib alone. The investigators reported an overall survival benefit appreciated as early as week 24 versus ruxolitinib, which has not been shown before for a ruxolitinib combination, and transformation to AML was rare (1.7% in both arms). Because regulators typically require both co-primary endpoints, the spleen-only symptom result still complicates the regulatory picture. Full results are published in the Journal of Clinical Oncology.
Luspatercept (activin receptor ligand trap) added to background JAKi therapy in MF patients with red cell transfusion dependence. It works downstream of EPO signalling and is already approved in MDS and beta-thalassaemia.
Why it matters: Anaemia in MF is debilitating and often undertreated once a patient is stabilised on a JAKi, with limited current options. Adding luspatercept without changing the JAKi is the practical advantage.
A monoclonal antibody targeting the neoantigenic mutant-CALR C-terminus, present in roughly 25% of MF and 30% of ET. EHA 2026 data showed spleen responses, anaemia improvement, and molecular responses (VAF reduction) in MF, both as monotherapy and with ruxolitinib. In ET, 87% of patients achieved a haematologic response (70% complete), reached rapidly (about 2 weeks) and durable (median response duration around 23 weeks).
Interpretation: Unlike JAK inhibitors, which suppress signalling without targeting the clone, this is the first therapy to exploit the CALR mutation as a direct tumour antigen. Molecular responses suggest genuine cytoreductive activity. If durable, this could shift CALR-mutant MPN from symptom control toward disease modification.
Ropeginterferon alfa-2b vs anagrelide in high-risk essential thrombocythaemia. Interferon preferentially suppresses the JAK2 or CALR-mutant clone and can achieve molecular remission, whereas anagrelide lowers platelets only without targeting the clone.
Interpretation: If the 2-year data confirm durable haematological and molecular benefit alongside favourable thrombosis and bleeding outcomes, the case strengthens for ropeg as a preferred cytoreductive agent in younger high-risk ET where disease modification and pregnancy compatibility matter.
EPO-PRETAR (phase 3): confirms erythropoietin as the first-line backbone for anaemia in lower-risk MDS with serum EPO below 500 IU/L. Useful validation for guideline adherence.
Ofirnoflast (PDE4 inhibitor): early-phase data showing erythroid responses in difficult-to-treat lower-risk MDS, including RARS / SF3B1-mutated subtypes.
CALR mutation status in MPN is moving from a purely prognostic marker toward identifying a therapeutically distinct population, echoing the trajectory of BCR-ABL testing in CML.
This argues for systematic CALR testing in MPN, though the antibody approach is not yet approved.
The first phase 3 superiority readout for a non-covalent BTK inhibitor.
Fixed-duration pirtobrutinib (non-covalent BTKi) plus venetoclax-rituximab (PVR) vs venetoclax-rituximab (VR) in previously treated CLL or SLL. Primary endpoint: IRC-assessed PFS.
Interpretation: The first non-covalent BTK inhibitor to show phase 3 superiority head-to-head. Around 80% of patients had already received a covalent BTK inhibitor, and the control-arm PFS (about 72%) was lower than in earlier venetoclax-rituximab studies, pointing to a high-risk population. The non-covalent mechanism overcomes the common C481S resistance mutation, and this trial suggests benefit even without prior BTKi failure. Results are to be published in the Lancet.
For previously BTKi-treated patients (ibrutinib, acalabrutinib, zanubrutinib), pirtobrutinib-based combinations are now strongly supported by phase 3 data.
For BTKi-naive relapsed patients, the PVR triplet may offer greater depth of response than the VR doublet. Pirtobrutinib tolerability is generally favourable, with lower rates of atrial fibrillation and hypertension than ibrutinib.
A next-generation CELMoD doubling PFS, a bispecific tested in pre-malignant disease, and a GPRC5D-directed phase 3.
Mezigdomide (CELMoD) plus carfilzomib-dexamethasone (MeziKd) vs carfilzomib-dexamethasone (Kd) in relapsed/refractory myeloma. Primary endpoint: PFS.
Interpretation: Mezigdomide binds cereblon more selectively than lenalidomide or pomalidomide and retains activity in IMiD-refractory settings. Doubling median PFS is a compelling result, building on SUCCESSOR-1. Results were published in the Lancet on 14 June 2026; the working-notes 95% CI of 0.36 to 0.63 should be confirmed against the published paper, as one congress report listed an upper bound of 0.83.
Teclistamab (BCMA x CD3 bispecific) vs lenalidomide-dexamethasone (Rd) in high-risk smouldering myeloma. The first randomised trial of a bispecific in smouldering disease.
Interpretation: A striking depth-of-response difference in a setting where early intervention has been debated. Potentially paradigm-shifting, but this is phase 2 with a relatively small sample.
GPRC5D is highly and homogeneously expressed on myeloma cells with limited critical-tissue expression. Talquetamab is already approved in later-line RRMM. The phase 3 talquetamab-versus-DPd programme is MonumenTAL-3.
The first positive frontline DLBCL readout since rituximab, and a first-in-human in vivo CAR-T signal.
Tafasitamab (anti-CD19) plus lenalidomide plus R-CHOP vs R-CHOP plus placebo in previously untreated IPI high-intermediate or high-risk DLBCL or high-grade B-cell lymphoma. Primary endpoint: investigator-assessed PFS.
Interpretation: The first positive phase 3 to improve on R-CHOP in newly diagnosed high-risk DLBCL since rituximab, with an 8.2% absolute 24-month PFS gain, and a tighter hazard ratio in centrally confirmed subtypes.
Dose-escalation of an in vivo (non-ex-vivo manufactured) CD19/CD20 dual-targeting CAR-T in relapsed/refractory B-cell NHL. The construct is delivered directly to the patient, reprogramming T-cells in situ and avoiding apheresis and weeks of manufacturing. Median time from consent to infusion was 17.5 days.
Interpretation: A potentially transformative delivery approach, with no neurotoxicity observed and dual targeting designed to reduce antigen escape.
Targeted therapy reaching conditions previously managed with broad immunosuppression.
Nipocalimab (anti-FcRn) blocks FcRn-mediated IgG recycling, accelerating clearance of pathogenic anti-red-cell IgG in warm AIHA. The primary endpoint was a stringent durable haemoglobin response sustained from week 16 to 24 without rescue.
Interpretation: An important positive trial in a condition with no approved targeted therapy in Europe. The stringent endpoint understates clinical benefit, and the steroid-sparing effect matters for long-term morbidity. Pharmacodynamic data showed roughly 60 to 70% total IgG reduction correlating with haemoglobin improvement.
BCMA-directed CAR-T targeting the plasma cells that produce pathogenic anti-platelet IgG in refractory primary ITP.
Interpretation: A landmark proof-of-concept for CAR-T in autoantibody-mediated disease. BCMA targeting depletes long-lived plasma cells more completely than CD19, which can achieve deep drug-free remission that current treatments cannot.
A PK activator with a clear haemoglobin signal but an unmet crisis-rate endpoint.
Oral pyruvate kinase activator in sickle cell disease. PK activation reduces 2,3-DPG and sickling precursors, raises ATP, and improves red cell survival. Already approved for PK deficiency.
Interpretation: Another split primary result. The haemoglobin and haemolysis signals are clear, but the overall crisis-rate reduction did not reach significance. Haemoglobin responders did show lower crisis and hospitalisation rates, suggesting that not all patients are PK-pathway dependent and that responder selection matters, though responders cannot yet be predicted upfront.
Sickle cell management has broadened quickly. Hydroxyurea, voxelotor, crizanlizumab, and L-glutamine are established, and gene therapy (lovotibeglogene autotemcel and exagamglogene autotemcel) is now available for eligible patients.
Mitapivat would add an oral, well-tolerated, mechanistically distinct option. Its potential advantage is a mechanism that is not HbS-specific, so it may work across HbSS, HbSC, and HbS-beta-thalassaemia, though the unmet crisis endpoint tempers expectations.
Practice-confirming GVHD prophylaxis data and an early concept to boost bispecific killing.
Definitive phase 3 validation that ATG-based GVHD prophylaxis should not be omitted in HLA-compatible unrelated donor transplantation, even with modern calcineurin-inhibitor prophylaxis.
Interpretation: Settles the debate about whether ATG still adds value in well-matched unrelated donor HCT. It remains standard. The next comparative question is ATG versus post-transplant cyclophosphamide in 10/10 MUD transplant.
CD5 is an inhibitory receptor on T-cells. Blocking it amplifies T-cell killing when combined with bispecific T-cell engagers, a potentially generalisable strategy across myeloma, NHL, and ALL.
Interpretation: A biological approach to T-cell exhaustion and limited killing efficiency in the immunosuppressive tumour microenvironment.
Rapid comparison within the busiest disease areas, plus a scorecard for the split-endpoint trials that defined the congress.
| Trial | Target | Result | Practice-changing now? |
|---|---|---|---|
| SENTRY | XPO1 (selinexor) + ruxolitinib | Spleen met (SVR35), symptoms not met; early OS signal | Not yet |
| INDEPENDENCE | Activin receptor ligand trap (luspatercept) | Anaemia / transfusion focus; specifics not verified here | Watch |
| INCA033989 | Mutant CALR antibody | Clinical and molecular responses; phase 1 | Potentially |
| Trial | Bispecific / target | Setting | Status |
|---|---|---|---|
| ImmunoPRISM | Teclistamab (BCMA) | High-risk smouldering myeloma | Phase 2, investigational |
| MonumenTAL-3 | Talquetamab (GPRC5D) | Relapsed/refractory, vs DPd | Watch |
| MajesTEC-9 | Teclistamab (BCMA), monotherapy | Earlier relapse, vs PVd or Kd | ASCO 2026, not EHA |
| Trial | Primary / co-primary | The other endpoint | Take-home |
|---|---|---|---|
| PASHA | OS not met (HR 1.02) | EFS / RFS trend favours gilteritinib | Midostaurin remains standard |
| SENTRY | SVR35 met (P<0.0001) | Symptom score not met (P=0.825) | Smaller spleen, symptoms unchanged |
| RISE UP | Haemoglobin response met | Pain-crisis rate not met (P=0.12) | Anti-haemolytic, crisis benefit unproven |
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Seventeen trials and programmes across eight areas, as summarised in the working notes.
Sorted by the nature of the reported result, not by clinical recommendation.
Deep MRD-negativity is recurring as the therapeutic target across disease areas in these notes.
BRUIN CLL-322: undetectable MRD at 10⁻⁶ of 52.1% vs 35.0% at end of treatment.
10⁻⁶ImmunoPRISM: MRD-negativity 81% vs 0% in high-risk smouldering disease.
10⁻⁵MonumenTAL-3: talquetamab-based regimens tested against the DPd backbone for depth of response.
Depth endpointMenin inhibitor combinations pursuing deep responses in NPM1-mutated disease.
MRD-drivenNew or expanding molecular and antigen targets featured across the congress notes.
A pragmatic split based only on what the working notes state. Local policy, licensing, and MDT discussion still govern any change in practice.
Six recurring threads drawn directly from the closing notes of the congress summary.
SENTRY, RISE UP, and PASHA all used co-primary or dual-endpoint designs where one was met and one was not, creating regulatory ambiguity and a risk of improving biology without symptoms, or the reverse.
Across CLL, myeloma, and AML, deep MRD-negativity is becoming the therapeutic goal rather than response or PFS alone, which calls for MRD testing embedded in routine pathways.
Teclistamab in high-risk smouldering myeloma and BCMA CAR-T in ITP show bispecifics reaching pre-malignant and autoimmune disease, while MonumenTAL-3 pushes talquetamab into earlier myeloma lines, raising ethical and safety questions about treating patients who may never progress.
LB2501 and REVSTAR-123 point toward cellular therapy that sidesteps the manufacturing bottleneck. The signals are early but compelling, likely 5 to 10 years from routine use.
INCA033989 is the first mutation-specific therapy in MPN, making CALR testing potentially predictive rather than only prognostic, echoing the BCR-ABL story in CML.
wAIHA (nipocalimab) and ITP (BCMA CAR-T) now have targeted trial data, with the FcRn mechanism validated across several antibody-mediated conditions.
Short teaching points distilled from the data above. Each is grounded in a specific trial.
Not every biologically superior drug improves overall survival.PASHA: gilteritinib matched but did not beat midostaurin for OS.
MRD is becoming the common language across haematology.BRUIN CLL-322 and the myeloma trials measured depth in the same terms.
Targeting the clone matters more than controlling the count.INCA033989 in CALR-mutant MPN, and ropeginterferon over anagrelide.
Cellular therapy is moving from bespoke manufacturing towards scalable delivery.LB2501 in vivo CAR-T and REVSTAR-123 off-the-shelf allogeneic CAR-T.
A smaller spleen is not the same as a patient who feels better.SENTRY met spleen response but not the symptom endpoint.
Treating disease earlier raises the bar for proving benefit outweighs harm.ImmunoPRISM moved bispecific therapy into pre-malignant smouldering myeloma.