This week in Hematology, we spotlight the most relevant updates, approvals, and progress driving the biopharma space.
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In Today’s Newsletter
🎓 ASH graduate awards for MDS & infant leukemia projects [1] [US • 5 Dec 2025]
Context: ASH Graduate Hematology and Hematology Inclusion Pathway awards (US$40k/year for two years) support PhD trainees with strong preliminary data in hematology.
Key point:
Elana Thieme: uses long-read single-cell RNA-seq to map lineage-specific alternative splicing in SRSF2-mutant MDS from stem through progenitor compartments.
Mark Mendoza: CRISPR models of KMT2A-rearranged infant leukemia in cord blood–derived and iPSC-derived hematopoietic cells to study the pre-leukemic phase and epigenetic rewiring.
Implication: Deep mechanistic work that can feed future target discovery, risk stratification, and early detection strategies in MDS and high-risk pediatric leukemias.
🧬Long-term transplant outcomes in sickle cell disease [2] [US • 7 Dec 2025]
Context: Largest and most comprehensive analysis to date (>1,000 patients) of hematopoietic cell transplantation (HCT) in sickle cell disease.
Key point: Most transplanted patients are alive, no longer show SCD symptoms, and have few late effects years after HCT, confirming durable benefit with acceptable long-term safety in real-world–like cohorts.
Implication: Provides robust data to support shared decision-making with families considering HCT vs lifelong disease-modifying therapies in SCD.
🧪 AstraZeneca’s expanded hematology & cell therapy program at ASH [3] [US • 4 Dec 2025]
Context: 65 abstracts (15 oral) across T-cell engagers, CAR-T, BTK inhibition, complement biology, and eosinophilic disease at the 67th ASH Annual Meeting.
Key point:
Surovatamig (CD19xCD3): 3-year FIH FL data, plus R/R B-ALL and DLBCL updates.
AZD0120 (BCMAxCD19 CAR-T): Initial DURGA-1 R/R MM data and IITs in high-risk newly diagnosed MM.
CALQUENCE: Long-term MCL (ECHO) and CLL (AMPLIFY, TrAVeRse) data.
ULTOMIRIS & VOYDEYA: HSCT-TMA pediatric cohort and PNH extravascular hemolysis subanalyses.
Implication: AZ is positioning itself as a multi-modality player spanning classic and cellular hematology, which will matter for future combination and sequencing options.
🧱 Bridging response predicts cilta-cel outcomes in CARTITUDE-4 [4] [US • 7 Dec 2025]
Context: CARTITUDE-4 in relapsed, lenalidomide-refractory MM; 196 patients ultimately received cilta-cel after DPd or PVd bridging.
Key point: Patients achieving ≥PR with bridging had substantially better PFS/OS and fewer fatal AEs versus those with <PR; VGPR+ responders showed ~76% PFS and 85% OS at 30 months, with lower infections and less prolonged cytopenias and no delayed Parkinson-like neurotoxicity.
Implication: Bridging therapy is strategic, not passive—choosing and tailoring regimens to maximize response before CAR-T can materially alter cilta-cel efficacy and safety.
🤖 AI in palliative oncology for hematologic malignancies [5] [US • 3 Dec 2025]
Context: Narrative review on AI applications in palliative care, with emphasis on leukemia, lymphoma, and multiple myeloma.
Key point: AI/ML tools can:
Predict short-term mortality, trigger earlier palliative consults, and document goals-of-care via NLP.
Classify leukemia/lymphoma from images, refine MRD and relapse risk, and predict transplant complications.
Support symptom management (pain, fatigue, distress) via EHR, wearable, and speech/text data—while raising strong concerns about bias, transparency, and the need for human oversight.
Implication: Expect gradual integration of AI into heme-onc palliative workflows, but adoption must be cautious, equity-focused, and clinician-led.
Jaypirca (pirtobrutinib) vs Imbruvica (ibrutinib) in CLL/SLL 🔄 [6] [Global • 7 Dec 2025]
Context: Phase 3 BRUIN CLL-314 randomized 662 BTKi-naïve CLL/SLL patients (treatment-naïve or R/R) to pirtobrutinib vs ibrutinib.
Key point:
Primary endpoint met: pirtobrutinib non-inferior for ORR and numerically higher (87.0% vs 78.5%).
PFS immature but trending in favor of pirtobrutinib, especially in treatment-naïve (HR ~0.24 ≈76% risk reduction).
Lower rates of atrial fibrillation/flutter and hypertension vs ibrutinib, with fewer AE-driven dose reductions and discontinuations.
Implication: First randomized covalent vs non-covalent BTKi comparison suggests pirtobrutinib may become a preferred BTKi in earlier CLL/SLL lines, subject to full PFS/OS and guideline/regulatory shifts.
🩸 DISC-0974 improves anemia in myelofibrosis (RALLY-MF Phase 2) [7] [US • 6 Dec 2025]
Context: Open-label Phase 2 RALLY-MF trial of DISC-0974 (hepcidin/iron-pathway–targeting antibody) in 47 MF patients with anemia (34 evaluable), with and without background JAK inhibitors.
Key point:
75% hepcidin reduction with increased serum iron.
nTD: 63% achieved ≥1 g/dL Hb rise for ≥12 weeks; 50% had ≥1.5 g/dL rise.
TD-Low: 71% achieved 16-week transfusion independence.
TD-High: majority with adequate follow-up had ≥50% transfusion reduction; early signals of ≥12-week TI.
Generally well tolerated; few treatment-related AEs.
Implication: Potential first-in-class approach to specifically treat MF-associated anemia, a major unmet need not addressed by current JAKi.
💡 ANKTIVA as potential “hematologic support therapy” [8] [US • 7 Dec 2025]
https://oncodaily.com/voices/patrick-soon-shiong-423618
Context: Commentary from Patrick Soon-Shiong on X (via OncoDaily) about N-803 (ANKTIVA), an IL-15 superagonist currently approved in NMIBC.
Key point: Proposes exploring ANKTIVA as an adjunctive “hematologic support therapy” analogous to EPOGEN or NEUPOGEN—co-administered with standard oncologic treatments to maintain NK and T-cell numbers, rather than as a replacement antitumor therapy. Regulatory oversight might fall under non-oncology hematology divisions if pursued.
Implication: Conceptual at present, but hints at a new development path where immune maintenance is treated as a dedicated supportive-care indication.
🌱 EndRAD: Non-TBI conditioning for NGS-MRD–negative B-ALL before HCT [9] [US • 7 Dec 2025]
https://www.medpagetoday.com/meetingcoverage/ashhematology/118875
Context: Phase 2 EndRAD trial across 45 North American centers in pediatric/AYA B-ALL (age 1–31) who were NGS-MRD negative in CR1/CR2 before allogeneic HCT.
Key point:
With non-TBI conditioning (mainly busulfan + fludarabine + thiotepa), 2-year EFS was 76.3% and OS 82.0% at 2.3-year median follow-up.
Relapse and non-relapse mortality each 12%; NGS-MRD positivity post-HCT predicted worse outcomes.
Results compare favorably to CIBMTR TBI-based benchmarks, particularly for older children/young adults.
Implication: For carefully selected NGS-MRD–negative B-ALL patients, non-TBI conditioning emerges as a viable way to reduce long-term TBI toxicity without compromising survival.
💉 Breyanzi approved for relapsed/refractory marginal zone lymphoma [10] [US • 4 Dec 2025]
Context: Breyanzi (lisocabtagene maraleucel) is a CD19 CAR-T already approved in several large B-cell lymphoma indications; marginal zone lymphoma remained unserved by CAR-Ts.
Key point: In the MZL cohort of TRANSCEND FL (third-line+ setting, n=66 for primary efficacy), Breyanzi achieved ORR 95.5%, CR 62.1%, and median DOR not reached with 90.1% of responders still in response at 24 months, with a safety profile consistent with prior experience (mostly low-grade CRS and manageable neurotoxicity).
Implication: Establishes the first CAR-T option for adult R/R MZL and expands Breyanzi’s footprint as the CD19 CAR-T with the broadest labeled range of B-cell malignancies.
⚡ AZD0120 dual BCMAxCD19 FasTCAR in relapsed/refractory MM [11] [US • 7 Dec 2025]
Context: Phase 1b/2 DURGA-1 trial of AZD0120, a dual BCMA/CD19 CAR-T manufactured via FasTCAR (no ex vivo expansion, all expansion in vivo) in heavily pretreated MM.
Key point:
Median follow-up 3.9 months; ORR 96%, with 78.3% CR/sCR and 17.4% PR.
MRD negativity (<10⁻⁵) at 1 month in 94% of evaluable patients.
Prior BCMA CAR-T/engager exposure allowed; ORR 100% and CR/sCR 80% in those previously treated with BCMA CAR-T.
CRS in 62% (mostly grade 1–2, median onset ~9 days), one grade 1 ICANS, no delayed neurotoxicity; ~35% received infusion in outpatient setting.
Median 14 days apheresis→release and 28 days to infusion, with 100% in-house manufacturing success after transition.
Implication: Combines dual-antigen targeting with rapid manufacturing and outpatient-friendly safety, positioning AZD0120 as a strong next-gen CAR-T contender in the MM space.
Why it matters
- Transplant strategy is being refined, not replaced: SCD data and EndRAD support more personalized HCT—curative intent with improved long-term risk framing.
- BTKi and CAR-T landscapes are getting crowded and more nuanced: Head-to-head BTKi data (pirtobrutinib vs ibrutinib) and new CAR-T indications (MZL, dual-target MM) will affect sequencing and earlier-line use.
- Supportive hematology is expanding: From MF anemia (DISC-0974) to conceptual immune maintenance (ANKTIVA), supportive-care categories may widen beyond red cells and neutrophils.
- AI and bridging strategies highlight “how” care is delivered: CARTITUDE-4 and AI palliative applications show that optimization of timing, bridging, and symptom management can markedly change real-world outcomes.
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FAQ
Does BRUIN CLL-314 make pirtobrutinib the new standard BTKi?
Not yet automatically, but the trial shows non-inferior, numerically higher ORR, PFS trending in favor of pirtobrutinib—especially in treatment-naïve—and fewer cardiac AEs vs ibrutinib [6]. Guidelines and regulators will determine how quickly practice moves.
How strong is the case for non-TBI conditioning in B-ALL now?
EndRAD suggests that NGS-MRD–negative pediatric/AYA B-ALL patients can achieve 2-year EFS/OS similar to TBI-based historical cohorts with non-TBI regimens, supporting individualized, toxicity-sparing strategies where MRD tools and transplant expertise exist [9].
What’s new with Breyanzi in marginal zone lymphoma?
It is now the first and only FDA-approved CAR-T for adult R/R MZL, with ~96% ORR and durable responses at 24 months in TRANSCEND FL, expanding definitive treatment options in this indolent but relapsing lymphoma [10].
Is DISC-0974 ready for routine MF anemia management?
Not yet—RALLY-MF is Phase 2 and data are early—but it shows consistent Hb gains and transfusion reductions across subgroups, including on JAKi, with a tolerable safety profile, justifying further development [7].
Is ANKTIVA actually approved as a support therapy?
No. The “hematologic support therapy” framing is a conceptual proposal from Soon-Shiong, not an approved indication. Any such use would require formal clinical trials and regulatory review [8].
Entities / Keywords
SRSF2; myelodysplastic syndromes; KMT2A-rearranged leukemia; hematopoietic cell transplantation; sickle cell disease; AstraZeneca; surovatamig (AZD0486); AZD0120; CALQUENCE (acalabrutinib); ULTOMIRIS (ravulizumab); VOYDEYA (danicopan); CARTITUDE-4; cilta-cel (ciltacabtagene autoleucel); DPd; PVd; artificial intelligence; machine learning; pirtobrutinib (Jaypirca); ibrutinib (Imbruvica); BRUIN CLL-314; chronic lymphocytic leukemia; small lymphocytic lymphoma; Disc Medicine; DISC-0974; myelofibrosis; anemia; ANKTIVA (N-803); EndRAD; non-TBI conditioning; busulfan; fludarabine; thiotepa; NGS-MRD; B-ALL; Breyanzi (lisocabtagene maraleucel; liso-cel); marginal zone lymphoma; TRANSCEND FL; multiple myeloma; FasTCAR; BCMA; CD19; DURGA-1.
References
- https://www.fredhutch.org/en/news/center-news/2025/12/american-society-for-hematology-graduate-awards-2025.html
- https://www.msn.com/en-gb/health/other/new-evidence-shows-hematopoietic-cell-transplantation-offers-durable-relief-for-sickle-cell-disease/ar-AA1RSiS5
- https://www.businesswire.com/news/home/20251204822773/en/AstraZeneca-advances-hematology-and-cell-therapy-ambition-with-largest-ever-presence-at-ASH
- https://www.pharmacytimes.com/view/bridging-response-emerges-as-key-predictor-of-cilta-cel-outcomes-in-cartitude-4
- https://www.cancernetwork.com/view/the-role-of-artificial-intelligence-in-palliative-oncology-zeroing-in-on-hematologic-malignancies
- https://investingnews.com/lilly-s-jaypirca-met-its-primary-endpoint-in-first-of-its-kind-head-to-head-phase-3-study-versus-imbruvica/
- https://www.globenewswire.com/news-release/2025/12/06/3201048/0/en/Disc-Medicine-Presents-Positive-Initial-Data-from-RALLY-MF-Phase-2-Trial-in-Patients-with-Myelofibrosis-MF-and-Anemia-at-the-67th-American-Society-of-Hematology-ASH-Annual-Meeting.html
- https://oncodaily.com/voices/patrick-soon-shiong-423618
- https://www.medpagetoday.com/meetingcoverage/ashhematology/118875
- https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibbs-Breyanzi-Approved-by-the-U-S–FDA-as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Marginal-Zone-Lymphoma-MZL/default.aspx
- https://www.cgtlive.com/view/fastcar-manufactured-bcmaxcd19-car-t-cell-therapy-shows-promise-for-multiple-myeloma