July 2026 in Hematology: 15 Developments That Advanced—and Challenged—Patient Care

July 2026 brought consequential developments across malignant and nonmalignant hematology, including expanded gene therapy access for young children, a new precision-engineered approach to matched-donor transplantation, updated pediatric anticoagulation guidance, and new administration options for multiple myeloma and bleeding disorders. Encouraging findings involving bispecific antibodies, Bruton tyrosine kinase (BTK) inhibition, CAR T-cell therapy, and hemophilia prophylaxis were balanced by setbacks for investigational treatments in sickle cell disease (SCD) and transplant-associated thrombotic microangiopathy (TA-TMA). Together, these developments reflect a hematology landscape increasingly shaped by targeted treatment, cellular and gene therapy, improved administration, individualized supportive care, and efforts to expand treatment access without compromising efficacy or safety.

FDA Expands Casgevy Approval to Children as Young as 2 Years

The FDA expanded the approval of exagamglogene autotemcel (Casgevy; Vertex Pharmaceuticals/CRISPR Therapeutics) to patients aged 2 years and older with SCD and recurrent vaso-occlusive crises or transfusion-dependent β-thalassemia, making it the first gene therapy approved for children with SCD who are this young. The CRISPR/Cas9-edited autologous cell therapy was previously limited to patients 12 years and older. By extending eligibility to younger children, the decision creates an opportunity to intervene before patients accumulate irreversible organ damage and other complications associated with recurrent vaso-occlusion or chronic transfusion dependence.¹

However, treatment still requires stem cell mobilization, myeloablative conditioning, specialized manufacturing, and care at an authorized treatment center.¹ These requirements make patient selection, caregiver education, supportive care, and long-term monitoring critical responsibilities for the multidisciplinary team.

Tregzi Introduces a New Approach to Matched-Donor Stem Cell Transplantation

The FDA approved allogeneic regulatory T-cell–based immunotherapy with hematopoietic stem and progenitor cells and T cells-vldq (Tregzi; Orca Bio) for use in matched-donor hematopoietic stem cell transplantation in adults with hematologic malignancies.²

Although the approval was announced June 30, its transition toward clinical availability and implementation occurred throughout July, with ordering expected to begin by the end of the month. The precision-engineered product separates donor cells into regulatory T cells, stem and progenitor cells, and conventional T cells to support hematopoietic and immunologic reconstitution while reducing graft-versus-host disease (GVHD). In the phase 3 Precision-T trial (NCT05316701), approximately 78% of patients receiving Tregzi were alive and free from moderate-to-severe chronic GVHD at 1 year compared with 38% receiving a conventional transplant.²

The therapy could reshape matched-donor transplantation, although its cost, manufacturing requirements, logistics, center readiness, and integration into conditioning and supportive care pathways will influence real-world uptake.

Wilate Prophylaxis Becomes Available Across All Pediatric Age Groups With von Willebrand Disease

The FDA expanded the indication for von Willebrand factor/coagulation factor VIII complex (human; Wilate, Octapharma) to include routine prophylaxis in children younger than 6 years with von Willebrand disease (VWD). The approval makes Wilate the first von Willebrand factor concentrate indicated for prophylaxis across all ages and forms of VWD.³

Findings from the phase 3 WIL-33 clinical trial (NCT04953884) showed a total annualized bleeding rate of about 4.6 among children younger than 6 years. Approximately 98.2% of reported bleeding episodes were minor, and 95.6% of treated episodes required only 1 infusion.^3,4 Extending prophylaxis to this population could support earlier prevention of recurrent bleeding, although individualized dosing, factor-level monitoring, venous access, caregiver training, and assessment of bleeding patterns remain important considerations for pharmacists and other clinicians.

Subcutaneous Isatuximab Offers a New Administration Option Across Multiple Myeloma Indications

The FDA approved subcutaneous isatuximab-irfc (Sarclisa Escena; Sanofi) for the multiple myeloma indications previously established for intravenous isatuximab.⁵ The 1400-mg dose may be delivered using the CirCLIQ on-body delivery system or manually with a syringe and infusion set.

In the phase 3 IRAKLIA trial (NCT05405166), subcutaneous isatuximab plus pomalidomide and dexamethasone demonstrated noninferiority to the intravenous formulation, with overall response rates of approximately 71.1% and 70.5%, respectively. Additional studies reported overall response rates of 79.7% with subcutaneous isatuximab plus carfilzomib and dexamethasone and 97.3% with subcutaneous isatuximab plus bortezomib, lenalidomide, and dexamethasone in transplant-ineligible, newly diagnosed disease.⁵

The approval could reduce chair time and infusion-resource demands while expanding administration options across several disease settings.

FDA Grants Priority Review to Mitapivat for Sickle Cell Disease

The FDA granted priority review to a supplemental new drug application for mitapivat (Aqvesme; Agios Pharmaceuticals) in SCD, with a Prescription Drug User Fee Act target date of November 1, 2026. Mitapivat is an oral pyruvate kinase activator designed to improve red blood cell energy metabolism, increase hemoglobin, and reduce hemolysis.⁶

The application is supported by findings from the phase 3 RISE UP trial, which evaluated mitapivat in patients with SCD. If approved, mitapivat would provide an oral, nongene therapeutic option targeting the metabolic dysfunction of sickled red blood cells. The regulatory milestone is particularly notable as the field seeks treatments that may be more accessible than intensive curative approaches while addressing anemia, hemolysis, and disease-related complications.⁶

Development of Tebapivat in Sickle Cell Disease Is Discontinued

Agios Pharmaceuticals announced that it would not advance the investigational pyruvate kinase activator tebapivat in SCD following results from a phase 2 trial. Although treatment demonstrated hematologic activity, including improvements in hemoglobin and markers of hemolysis, the findings did not establish sufficient differentiation from other pyruvate kinase activators to support continued development.⁷

The decision illustrates that biological activity alone may not be adequate in an increasingly competitive therapeutic landscape. New SCD treatments must demonstrate clinically meaningful benefits across outcomes such as pain crises, anemia, hemolysis, quality of life, safety, treatment burden, and access. The discontinuation also increases the importance of the ongoing regulatory review for mitapivat and continued development of other oral, cellular, and gene-based approaches.

Denecimig Maintains Low Bleeding Rates in Long-Term Hemophilia A Study

Long-term phase 3 findings from the FRONTIER extension program showed that investigational denecimig (Mim8; Novo Nordisk) maintained low bleeding rates in children, adolescents, and adults with hemophilia A, regardless of factor VIII inhibitor status or dosing schedule. Denecimig is a next-generation bispecific antibody designed to mimic activated factor VIII by bridging activated factor IX and factor X.⁸

The extension findings were consistent with the established safety profile from the broader FRONTIER program and support the potential use of once-weekly or once-monthly subcutaneous prophylaxis. A biologics license application is under FDA review for routine prophylaxis in adult and pediatric patients with hemophilia A, with or without inhibitors. If approved, denecimig could offer another nonfactor prophylactic option with flexible administration for a broad population of patients with hemophilia A.⁸

Dual-Targeting Bispecific Therapy Produces Major Survival Benefits in Relapsed or Refractory Multiple Myeloma

Topline results from the phase 3 MonumenTAL-6 trial (NCT06208150) demonstrated substantial benefits with the bispecific antibody combination teclistamab-cqyv (Tecvayli; Janssen) plus talquetamab-tgvs (Talvey; Janssen) in adults with relapsed or refractory multiple myeloma who had received 1 to 4 previous lines of therapy, including lenalidomide and an anti-CD38 antibody.⁹

The regimen, which simultaneously targets B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D, reduced the risk of disease progression or death by 89% and the risk of death by 62% compared with investigator-selected standard therapy. Talquetamab plus pomalidomide also reduced the risk of progression or death by 73%.⁹

Although complete findings remain necessary to assess response durability, infections, cytopenias, cytokine release syndrome, neurotoxicity, and treatment discontinuation, the results support moving off-the-shelf T-cell–redirecting therapy into earlier treatment lines.

Cevostamab Shows Durable Activity in Heavily Pretreated Multiple Myeloma

Published phase 1 findings demonstrated encouraging activity with cevostamab, a first-in-class bispecific antibody targeting Fc receptor-homolog 5 on myeloma cells and CD3 on T cells. Among 167 heavily pretreated patients with relapsed or refractory multiple myeloma, the overall response rate was 44.3%, including a very good partial response or better rate of 25.7%. Among patients without previous BCMA-directed therapy, these rates increased to 60.6% and 39.4%, respectively. Median duration of response was 10.4 months overall and 19.7 months among BCMA-naive patients. Responses were maintained after completion of the approximately 12-month fixed-duration treatment course, and cytokine release syndrome was limited to grade 1 or 2 with the recommended step-up regimen.¹⁰

These findings support Fc receptor-homolog 5 as a potentially valuable alternative target in late-line disease, including after exposure to established BCMA-directed treatments.

Longer Lenalidomide Maintenance Does Not Improve Overall Survival in Standard-Risk Multiple Myeloma

Long-term results from the phase 3 ENDURANCE trial (NCT01863550) found no overall survival (OS) advantage from continuing lenalidomide maintenance until disease progression compared with stopping treatment after 2 years among patients with newly diagnosed, standard-risk multiple myeloma.¹¹

At a median follow-up of approximately 7 years, OS was 69.0% with indefinite maintenance and 68.6% with 2 years of treatment. Although longer maintenance delayed disease progression, it also extended treatment exposure and its associated adverse effects, costs, and quality-of-life burden.¹¹

The results do not establish one optimal duration for every patient but strengthen the rationale for shared decision-making based on disease risk, measurable residual disease status when available, tolerability, patient preference, financial burden, and the balance between progression-free survival (PFS) and OS.¹¹

Orelabrutinib Outperforms Chemoimmunotherapy in Previously Untreated CLL/SLL

Results from a randomized phase 3 trial showed that the selective BTK inhibitor orelabrutinib significantly improved PFS compared with chlorambucil plus rituximab in patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).¹²

At a median follow-up of about 21.4 months, median PFS was not reached with orelabrutinib and was 19.4 months with chemoimmunotherapy, representing an approximate 68% reduction in the risk of progression or death. The overall response rates were 90.1% and 79.2%, respectively.¹²

Grade 3 or higher treatment-related adverse events occurred in approximately 35.2% of patients receiving orelabrutinib and 60.2% receiving chlorambucil plus rituximab. Although orelabrutinib is not currently FDA approved, the findings add to evidence supporting targeted, chemotherapy-free approaches in frontline CLL/SLL.¹²

Ten-Year Findings Demonstrate the Potential Durability of CAR T-Cell Therapy in B-Cell Lymphoma

Long-term findings from an early anti-CD19 CAR T-cell therapy study demonstrated sustained remissions in some patients with heavily pretreated B-cell lymphoma.¹³

At a median follow-up of 10.1 years, 12 of 38 treated patients achieved a long-term response, and no relapses occurred beyond 5.4 years. Ten-year lymphoma-free survival was approximately 32% among patients with large B-cell lymphoma and 47% among those with follicular lymphoma, whereas OS was 17% and 50%, respectively. Among responders, estimated duration of response at 10 years was 54% for large B-cell lymphoma and 60% for follicular lymphoma.¹³

Although the small, early-phase cohort limits broad conclusions, the absence of late relapses provides important evidence that a single CAR T-cell infusion can produce decade-long disease control—and potentially cure—for a subset of patients.

Phase 3 Ravulizumab Trial Misses Primary End Point in Transplant-Associated TMA

Ravulizumab-cwvz (Ultomiris; Alexion/AstraZeneca) did not significantly improve 26-week event-free survival in the phase 3 ALXN1210-TMA-313 trial (NCT04543591) involving adults and adolescents with TA-TMA after hematopoietic stem cell transplantation. The primary end point measured survival without TMA-related clinical worsening or death.¹⁴

Although the study demonstrated a numerical trend favoring ravulizumab and no new safety signals, it did not achieve statistical significance. The result represents a setback in an area with substantial unmet need and no broadly established FDA-approved treatment. However, separate pediatric findings showed survival rates of 87.2% at 26 weeks and 73.4% at 52 weeks, and the manufacturer indicated that regulatory discussions for pediatric TA-TMA would continue.¹⁴

The divergent findings reinforce the clinical heterogeneity of TA-TMA and the importance of early identification and population-specific study designs.

ASH/ISTH Guidance Addresses Anticoagulant Prophylaxis in Pediatric Patients

Updated clinical practice guidance from the American Society of Hematology and International Society on Thrombosis and Haemostasis addressed anticoagulant prophylaxis in pediatric patients at risk for venous thromboembolism (VTE).¹⁵

The recommendations emphasize that prophylaxis decisions should reflect each patient’s thrombosis and bleeding risks because evidence remains limited and cannot necessarily be extrapolated from adult populations. The guidance evaluates pharmacologic and nonpharmacologic prophylaxis across hospitalized children and other clinical settings, supporting structured risk assessment rather than universal anticoagulant use.¹⁵

For pharmacists, the recommendations reinforce the importance of age- and weight-appropriate dosing, renal and hepatic function assessment, potential drug interactions, bleeding surveillance, administration feasibility, and communication with patients and caregivers.

Global Commission Calls for Better Hematologic Care for Women and Girls

A global commission highlighted persistent inequities affecting women and girls with anemia, bleeding disorders, thrombosis, and hematologic malignancies.¹⁶ The report identified delayed diagnosis, undertreatment, underrepresentation in clinical trials, and insufficient attention to menstruation, pregnancy, and the postpartum period as major barriers to equitable care. The authors called for improved clinician education, sex-specific research, stronger diagnostic pathways, greater access to therapies, and policies that recognize the disproportionate global burden of iron deficiency and other blood disorders among women.¹⁶

For pharmacists, the recommendations emphasize opportunities to identify untreated anemia, assess medication-related bleeding and thrombotic risks, support treatment during pregnancy, improve referral pathways, and advocate for more inclusive clinical research.

REFERENCES

1. FDA approves first gene therapy for young children with sickle cell disease. FDA. News release. July 1, 2026. Accessed July 31, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-young-children-sickle-cell-disease

2. FDA approves allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq for use in matched donor hematopoietic stem cell transplantation for adults with hematologic malignancies. FDA. News release. June 30, 2026. Accessed July 31, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-allogeneic-regulatory-t-cell-based-immunotherapy-hspc-and-t-cells-vldq-use-matched

3. Wilate. FDA. Updated July 23, 2026. Accessed July 31, 2026. https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/wilate

4. Octapharma USA announces expanded FDA approval of Wilate for von Willebrand disease prophylaxis in children younger than 6 years. Octapharma USA. News release. July 8, 2026. Accessed July 31, 2026. https://www.prnewswire.com/news-releases/octapharma-usa-announces-expanded-fda-approval-of-wilate-for-von-willebrand-disease-prophylaxis-in-children-younger-than-6-years-302820881.html

5. US Food and Drug Administration. FDA approves isatuximab-irfc for subcutaneous injection for multiple myeloma indications. FDA. News release. July 9, 2026. Accessed July 31, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-isatuximab-irfc-subcutaneous-injection-multiple-myeloma-indications

6. US FDA grants priority review to Agios’ sNDA for mitapivat in sickle cell disease. Agios Pharmaceuticals. News release. July 7, 2026. Accessed July 31, 2026. https://investor.agios.com/news-releases/news-release-details/us-fda-grants-priority-review-agios-snda-mitapivat-sickle-cell

7. Agios Pharmaceuticals. Agios provides update on phase 2 trial of tebapivat in sickle cell disease. Agios Pharmaceuticals. News release. July 21, 2026. Accessed July 31, 2026. https://investor.agios.com/news-releases/news-release-details/agios-provides-update-phase-2-trial-tebapivat-sickle-cell

8. Novo Nordisk’s denecimig (Mim8) demonstrated positive results in long-term safety and efficacy in phase 3 hemophilia A FRONTIER extension study at ISTH 2026. PR Newswire. News release. July 11, 2026. Accessed July 31, 2026. https://www.prnewswire.com/news-releases/novo-nordisks-denecimig-mim8-demonstrated-positive-results-in-long-term-safety-and-efficacy-in-phase-3-hemophilia-a-frontier-extension-study-at-isth-2026-302823063.html

9. Tecvayli plus Talvey reduced the risk of disease progression or death by 89% and the risk of death by 62% in earlier-line relapsed/refractory multiple myeloma. Johnson & Johnson. News release. July 23, 2026. Accessed July 31, 2026. https://www.investor.jnj.com/investor-news/news-details/2026/TECVAYLI--TALVEY-reduced-the-risk-of-disease-progression-or-death-by-89-and-the-risk-of-death-by-62-in-earlier-line-relapsedrefractory-multiple-myeloma/default.aspx

10. Cohen AD, Richter J, Trudel S, et al. FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial. Nat Med (2026). doi:10.1038/s41591-026-04522-3

11. ECOG-ACRIN Cancer Research Group. E1A11/ENDURANCE clinical trial results summary. Updated July 20, 2026. Accessed July 31, 2026. https://ecog-acrin.org/wp-content/uploads/2025/09/E1A11_ClinTrialResultsSumm_EA-Web_v.14Aug2025.pdf

12. Li F, Zhou K, Xu W, et al. Orelabrutinib versus chemoimmunotherapy in treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma: a randomized, phase 3 trial. Sig Transduct Target Ther 11, 261 (2026). doi:10.1038/s41392-026-02818-x

13. Ruella M, Paruzzo L, Chong ER, et al. Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas. N Engl J Med. 2026;394(24):2440-2448. doi:10.1056/NEJMoa2518035

14. Update on phase III trial of Ultomiris in adults and adolescents with thrombotic microangiopathy after hematopoietic stem cell transplant. AstraZeneca. News release. July 27, 2026. Accessed July 31, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/update-on-ultomiris-phase-iii-trial-in-hsct-tma.html

15. Betensky M, Azzam M, Bercovitz R, et al. ASH/ISTH 2026 guidelines for anticoagulant prophylaxis in pediatric patients at risk of venous thromboembolism. Blood Adv. 2026;10(12):4303-4333. doi:10.1182/bloodadvances.2025019415

16. New global report outlines strategies to improve hematologic care for women. Cleveland Clinic. News release. July 13, 2026. Accessed July 31, 2026. https://newsroom.clevelandclinic.org/2026/07/13/new-global-report-outlines-strategies-to-improve-hematologic-care-for-women