This Week in Hematology — Oct 28, 2026
Generated Oct 28, 2026 · 11:40
The week's practice-changing Hematology research, summarized for clinicians.
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Efficacy and safety of mitapivat in patients with sickle cell disease (RISE UP): a phase 3, double-blind, global, randomised, placebo-controlled trial.
Mitapivat produced haemoglobin responses in 41 percent of sickle cell patients versus 3 percent on placebo, but did not significantly reduce the annualised rate of pain crises.
The Lancet · 2026 · PubMed
This week’s papers
- 01
Efficacy and safety of mitapivat in patients with sickle cell disease (RISE UP): a phase 3, double-blind, global, randomised, placebo-controlled trial.
Mitapivat produced haemoglobin responses in 41 percent of sickle cell patients versus 3 percent on placebo, but did not significantly reduce the annualised rate of pain crises.
Andemariam B et al. · The Lancet · 2026
From the briefingWe start with non-malignant hematology, where oral and targeted agents are reshaping how chronic haemolysis and bleeding disorders are managed. The headline paper is RISE UP in The Lancet, a phase 3, double-blind, placebo-controlled trial led by Andemariam testing mitapivat, an oral pyruvate kinase activator, in sickle cell disease [1]. Across 69 sites in 15 countries, 207 patients older than 16 with anaemia and recurrent pain crises were randomised two to one to mitapivat 100 milligrams twice daily or placebo. The trial had two primary endpoints, and the results split. For haemoglobin response, defined as a rise of at least one gram per decilitre, about 41 percent of patients on mitapivat responded compared with just 3 percent on placebo, a clear and statistically significant difference. But the annualised rate of sickle cell pain crises, about 2.6 on mitapivat versus 3.1 on placebo, did not differ significantly. Serious adverse events were actually less frequent on mitapivat, and only one was judged treatment related. So the evidence firmly supports mitapivat as a treatment for haemolytic anaemia in sickle cell disease, while the hoped-for reduction in vaso-occlusive crises was not demonstrated in this trial. Whether better haemoglobin translates into fewer long-term complications is a question the ongoing extension may help address.
If you only have time for one paper this week, make it RISE UP in The Lancet [1]. It is the first phase 3 evidence for a pyruvate kinase activator in sickle cell disease, settling that mitapivat meaningfully improves haemolytic anaemia while reopening the question of whether that alone changes the crisis burden.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 02
Clinical Experience of Iptacopan in Paroxysmal Nocturnal Hemoglobinuria.
In 151 real-world PNH patients, oral iptacopan raised haemoglobin durably, achieved transfusion independence in 88 percent, and worked regardless of prior bone marrow failure, without meningococcal infections.
Holt M et al. · American Journal of Hematology · 2026
From the briefingComplement inhibition offers a parallel story. Writing in the American Journal of Hematology, Holt and colleagues report real-world experience with iptacopan, the oral factor B inhibitor, in 151 patients with paroxysmal nocturnal hemoglobinuria treated in the United Kingdom and France [2]. Mean haemoglobin climbed by more than 20 grams per litre within three months and stayed there to two years; roughly three quarters of patients reached a haemoglobin of at least 120 grams per litre by one year, and close to nine in ten patients were transfusion independent. Importantly, patients with a history of bone marrow failure, a group thin in the registration trials, responded similarly. Breakthrough haemolysis occurred in under 7 percent of patients, there were no meningococcal or pneumococcal infections, and no thromboses. This is retrospective data with a median treatment duration of well under a year, so the authors themselves flag that longer follow-up is needed on infection risk, but it extends trial findings into a broader population.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 03
Combination of Thrombopoietin Receptor Agonists and Rituximab in Relapsed/Refractory Immune Thrombocytopenia: A Multicenter Real-World Study.
Combining thrombopoietin receptor agonists with rituximab in heavily pretreated immune thrombocytopenia yielded an 83 percent response rate and 30 percent treatment-free remission in a retrospective Chinese cohort.
Tian H et al. · Journal of Thrombosis and Haemostasis · 2026
From the briefingTian and colleagues describe 161 heavily pretreated patients with relapsed or refractory immune thrombocytopenia across six Chinese centres who received a thrombopoietin receptor agonist combined with rituximab [3]. The best overall response rate was 83 percent, and after nearly two years of follow-up, about 30 percent of patients achieved treatment-free remission. Intriguingly, adding rituximab restored platelet response in roughly three in ten patients who had been primarily refractory to their prior receptor agonist. Younger women, shorter disease duration, and a positive antinuclear antibody predicted remission, while low-dose rituximab predicted lower odds. As a retrospective, uncontrolled cohort it is hypothesis-generating rather than practice-defining.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 04
Emicizumab Prophylaxis in People with Haemophilia A: Summary of Over 13 Years of Safety Data on Thromboembolic Events and Thrombotic Microangiopathy.
Over 13 years, emicizumab-associated thrombotic microangiopathies occurred only with high-dose concurrent aPCC, and other thrombotic event rates matched background haemophilia A rates, supporting a stable safety profile.
Kelsch C et al. · Journal of Thrombosis and Haemostasis · 2026
From the briefingAnd Kelsch and colleagues summarise more than 13 years of emicizumab safety surveillance in haemophilia A [4]. Among 165 thrombotic events and thrombotic microangiopathies, all five microangiopathies were linked to concurrent activated prothrombin complex concentrate above 100 units per kilogram per day for at least 24 hours. Outside that setting, the thrombotic event rate in clinical trials was comparable to the background rate in people with haemophilia A drawn from a United States claims database, and many of the affected patients were older with existing cardiovascular risk factors. The data come from the manufacturer's safety database, but they reinforce a stable benefit-risk picture.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 05
Firstline treatment with ruxolitinib versus best available therapy in patients with polycythemia vera: results from the randomized RuxoBEAT trial.
First-line ruxolitinib did not improve six-month complete response over best available therapy in polycythemia vera, though it better controlled hematocrit, spleen size, pruritus and fatigue.
Koschmieder S et al. · Blood Cancer Journal · 2026
From the briefingOur second theme is the myeloproliferative neoplasms, where three papers ask how much current therapies really change the disease. In Blood Cancer Journal, Koschmieder and colleagues report RuxoBEAT, a randomised trial of first-line ruxolitinib versus best available therapy in polycythemia vera [5]. The primary endpoint, clinico-hematologic complete response at six months, was not met, with complete response rates of only around 2 to 3 percent in both arms. Secondary and exploratory analyses did favour ruxolitinib for hematocrit control, spleen size, pruritus, and fatigue, and patients stayed on ruxolitinib longer, though it was less effective at lowering platelets. With 78 patients and crossover allowed after six months, this is a negative trial on its primary question that leaves the door open to ruxolitinib's symptomatic advantages upfront.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 06
High Initial Dose and Accelerated vs. Slow Titration Ropeginterferon Alfa-2b for Polycythemia Vera: A Meta-Analysis.
Pooled non-randomised data suggest high-initial-dose accelerated ropeginterferon titration achieves faster hematologic and molecular responses in polycythemia vera than slow titration, without added toxicity, pending randomised confirmation.
Yacoub A et al. · Blood Advances · 2026
From the briefingA meta-analysis in Blood Advances from Yacoub and colleagues addresses ropeginterferon dosing in polycythemia vera [6]. Comparing a high initial dose and accelerated titration regimen, starting at 250 micrograms and reaching 500 micrograms within four weeks, against the labelled slow titration, the pooled data showed higher complete hematologic response rates at three, six, and twelve months, and better molecular responses, without detectable differences in adverse events or discontinuations. These are cross-study comparisons rather than head-to-head randomised data, and the authors explicitly call for prospective trials, but the analysis supports the rationale behind the faster schedule that is already gaining traction.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 07
New Drugs in Myelofibrosis: Incremental Progress in Symptom Management Without Disease Modification.
Ruxolitinib-based combinations in myelofibrosis improve spleen responses but not clearly symptoms or anaemia, while CALR-directed and TGF-beta pathway agents represent the more promising emerging approaches.
Gangat N et al. · American Journal of Hematology · 2026
From the briefingIn myelofibrosis, Gangat and colleagues offer a sober review in the American Journal of Hematology, framing new drugs as incremental progress in symptom management without disease modification [7]. Combinations of ruxolitinib with pelabresib, navitoclax, or selinexor improve spleen responses, but gains in symptoms and anaemia are less consistent and toxicity may rise. The authors point to CALR-directed therapies, notably INCA033989, as the most promising route to selective clone suppression, and to agents targeting TGF-beta signalling such as luspatercept for transfusion burden. They argue that future trials should prioritise transplantation, molecular response, and survival endpoints over spleen volume alone.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 08
Hematopoietic Cell Transplantation Outcomes in the Era of Post-Transplant Cyclophosphamide: Comprehensive Donor Analysis.
Among over 12,000 transplant recipients given post-transplant cyclophosphamide, matched siblings retained a survival edge after donor-age adjustment, but differences across donor types narrowed considerably.
Aljawai YM et al. · Blood Advances · 2026
From the briefingOur third theme covers transplantation and immunotherapy, and the risks that come with them. In Blood Advances, Aljawai and colleagues analysed more than 12,600 adults with acute leukaemia or myelodysplastic syndromes from the Center for International Blood and Marrow Transplant Research who received post-transplant cyclophosphamide-based prophylaxis [8]. After adjusting for donor age, matched siblings still led on overall survival, with mortality risk roughly 16 percent higher with matched unrelated donors and around 40 percent higher with haploidentical donors. All alternative donors carried less relapse but more non-relapse mortality and acute graft-versus-host disease, with similar chronic disease. Without donor-age adjustment, though, survival with matched and 7 of 8 mismatched unrelated donors was similar to siblings. The authors conclude that cyclophosphamide narrows donor differences and supports timely transplant with the best available donor, though as a registry analysis it cannot fully disentangle donor age from donor type.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 09
Molecular Underpinnings and Prevalence of Donor Cell-Derived Hematologic Neoplasms among Spanish Transplantation Centers.
Donor cell-derived neoplasms affected about 0.3 percent of Spanish allogeneic transplants, occurred mainly after related-donor grafts, and were frequently driven by inherited germline variants, especially DDX41.
Gabarros-Subira M et al. · Blood · 2026
From the briefingThat sibling advantage comes with a caveat raised in Blood by Gabarros-Subira and colleagues, who conducted a nationwide Spanish study of donor cell-derived hematologic neoplasms [9]. Prevalence was low overall, about 0.3 percent, but it was markedly higher after related-donor transplants than after unrelated ones, and diagnosis came a median of about four and a half years after transplant. Most cases were myeloid. Germline predisposition emerged as the dominant mechanism, with pathogenic variants found in ten cases, seven of them in DDX41, all after related-donor transplants. The authors argue this strengthens the case for germline evaluation at diagnosis and cascade screening of related donors, a recommendation resting on a small but well-characterised case series.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 10
Temporal trends in infectious risk among multiple myeloma patients treated with daratumumab: A meta-analysis.
Across six randomised myeloma trials, daratumumab increased severe and recurrent infections, with risk peaking in the first three months, while immunoglobulin replacement was rarely used.
Visram A et al. · British Journal of Haematology · 2026
From the briefingFinally, in the British Journal of Haematology, Visram and colleagues pooled individual patient data from six randomised trials, nearly 3,000 patients, to map infection risk with daratumumab in myeloma [10]. Daratumumab raised severe infections from about one in five patients to nearly three in ten, with risk concentrated in the first three months before plateauing, and recurrent infections were more common. Fewer than one in five patients with severe respiratory infections received immunoglobulin replacement. The findings identify an early window of vulnerability and support time-targeted prevention, though prophylaxis strategies themselves were not tested.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
The full briefing
This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.
Welcome to This Week in Hematology. This week we're covering 10 notable papers spanning new oral and targeted therapies in non-malignant hematology, a fresh look at treatment strategy in the myeloproliferative neoplasms, and the risks that come with transplantation and immunotherapy. Let's dive in.
We start with non-malignant hematology, where oral and targeted agents are reshaping how chronic haemolysis and bleeding disorders are managed. The headline paper is RISE UP in The Lancet, a phase 3, double-blind, placebo-controlled trial led by Andemariam testing mitapivat, an oral pyruvate kinase activator, in sickle cell disease [1]. Across 69 sites in 15 countries, 207 patients older than 16 with anaemia and recurrent pain crises were randomised two to one to mitapivat 100 milligrams twice daily or placebo. The trial had two primary endpoints, and the results split. For haemoglobin response, defined as a rise of at least one gram per decilitre, about 41 percent of patients on mitapivat responded compared with just 3 percent on placebo, a clear and statistically significant difference. But the annualised rate of sickle cell pain crises, about 2.6 on mitapivat versus 3.1 on placebo, did not differ significantly. Serious adverse events were actually less frequent on mitapivat, and only one was judged treatment related. So the evidence firmly supports mitapivat as a treatment for haemolytic anaemia in sickle cell disease, while the hoped-for reduction in vaso-occlusive crises was not demonstrated in this trial. Whether better haemoglobin translates into fewer long-term complications is a question the ongoing extension may help address.
Complement inhibition offers a parallel story. Writing in the American Journal of Hematology, Holt and colleagues report real-world experience with iptacopan, the oral factor B inhibitor, in 151 patients with paroxysmal nocturnal hemoglobinuria treated in the United Kingdom and France [2]. Mean haemoglobin climbed by more than 20 grams per litre within three months and stayed there to two years; roughly three quarters of patients reached a haemoglobin of at least 120 grams per litre by one year, and close to nine in ten patients were transfusion independent. Importantly, patients with a history of bone marrow failure, a group thin in the registration trials, responded similarly. Breakthrough haemolysis occurred in under 7 percent of patients, there were no meningococcal or pneumococcal infections, and no thromboses. This is retrospective data with a median treatment duration of well under a year, so the authors themselves flag that longer follow-up is needed on infection risk, but it extends trial findings into a broader population.
Two papers in the Journal of Thrombosis and Haemostasis round out this theme. Tian and colleagues describe 161 heavily pretreated patients with relapsed or refractory immune thrombocytopenia across six Chinese centres who received a thrombopoietin receptor agonist combined with rituximab [3]. The best overall response rate was 83 percent, and after nearly two years of follow-up, about 30 percent of patients achieved treatment-free remission. Intriguingly, adding rituximab restored platelet response in roughly three in ten patients who had been primarily refractory to their prior receptor agonist. Younger women, shorter disease duration, and a positive antinuclear antibody predicted remission, while low-dose rituximab predicted lower odds. As a retrospective, uncontrolled cohort it is hypothesis-generating rather than practice-defining. And Kelsch and colleagues summarise more than 13 years of emicizumab safety surveillance in haemophilia A [4]. Among 165 thrombotic events and thrombotic microangiopathies, all five microangiopathies were linked to concurrent activated prothrombin complex concentrate above 100 units per kilogram per day for at least 24 hours. Outside that setting, the thrombotic event rate in clinical trials was comparable to the background rate in people with haemophilia A drawn from a United States claims database, and many of the affected patients were older with existing cardiovascular risk factors. The data come from the manufacturer's safety database, but they reinforce a stable benefit-risk picture.
Our second theme is the myeloproliferative neoplasms, where three papers ask how much current therapies really change the disease. In Blood Cancer Journal, Koschmieder and colleagues report RuxoBEAT, a randomised trial of first-line ruxolitinib versus best available therapy in polycythemia vera [5]. The primary endpoint, clinico-hematologic complete response at six months, was not met, with complete response rates of only around 2 to 3 percent in both arms. Secondary and exploratory analyses did favour ruxolitinib for hematocrit control, spleen size, pruritus, and fatigue, and patients stayed on ruxolitinib longer, though it was less effective at lowering platelets. With 78 patients and crossover allowed after six months, this is a negative trial on its primary question that leaves the door open to ruxolitinib's symptomatic advantages upfront.
A meta-analysis in Blood Advances from Yacoub and colleagues addresses ropeginterferon dosing in polycythemia vera [6]. Comparing a high initial dose and accelerated titration regimen, starting at 250 micrograms and reaching 500 micrograms within four weeks, against the labelled slow titration, the pooled data showed higher complete hematologic response rates at three, six, and twelve months, and better molecular responses, without detectable differences in adverse events or discontinuations. These are cross-study comparisons rather than head-to-head randomised data, and the authors explicitly call for prospective trials, but the analysis supports the rationale behind the faster schedule that is already gaining traction.
In myelofibrosis, Gangat and colleagues offer a sober review in the American Journal of Hematology, framing new drugs as incremental progress in symptom management without disease modification [7]. Combinations of ruxolitinib with pelabresib, navitoclax, or selinexor improve spleen responses, but gains in symptoms and anaemia are less consistent and toxicity may rise. The authors point to CALR-directed therapies, notably INCA033989, as the most promising route to selective clone suppression, and to agents targeting TGF-beta signalling such as luspatercept for transfusion burden. They argue that future trials should prioritise transplantation, molecular response, and survival endpoints over spleen volume alone.
Our third theme covers transplantation and immunotherapy, and the risks that come with them. In Blood Advances, Aljawai and colleagues analysed more than 12,600 adults with acute leukaemia or myelodysplastic syndromes from the Center for International Blood and Marrow Transplant Research who received post-transplant cyclophosphamide-based prophylaxis [8]. After adjusting for donor age, matched siblings still led on overall survival, with mortality risk roughly 16 percent higher with matched unrelated donors and around 40 percent higher with haploidentical donors. All alternative donors carried less relapse but more non-relapse mortality and acute graft-versus-host disease, with similar chronic disease. Without donor-age adjustment, though, survival with matched and 7 of 8 mismatched unrelated donors was similar to siblings. The authors conclude that cyclophosphamide narrows donor differences and supports timely transplant with the best available donor, though as a registry analysis it cannot fully disentangle donor age from donor type.
That sibling advantage comes with a caveat raised in Blood by Gabarros-Subira and colleagues, who conducted a nationwide Spanish study of donor cell-derived hematologic neoplasms [9]. Prevalence was low overall, about 0.3 percent, but it was markedly higher after related-donor transplants than after unrelated ones, and diagnosis came a median of about four and a half years after transplant. Most cases were myeloid. Germline predisposition emerged as the dominant mechanism, with pathogenic variants found in ten cases, seven of them in DDX41, all after related-donor transplants. The authors argue this strengthens the case for germline evaluation at diagnosis and cascade screening of related donors, a recommendation resting on a small but well-characterised case series.
Finally, in the British Journal of Haematology, Visram and colleagues pooled individual patient data from six randomised trials, nearly 3,000 patients, to map infection risk with daratumumab in myeloma [10]. Daratumumab raised severe infections from about one in five patients to nearly three in ten, with risk concentrated in the first three months before plateauing, and recurrent infections were more common. Fewer than one in five patients with severe respiratory infections received immunoglobulin replacement. The findings identify an early window of vulnerability and support time-targeted prevention, though prophylaxis strategies themselves were not tested.
If you only have time for one paper this week, make it RISE UP in The Lancet [1]. It is the first phase 3 evidence for a pyruvate kinase activator in sickle cell disease, settling that mitapivat meaningfully improves haemolytic anaemia while reopening the question of whether that alone changes the crisis burden.
Here is what this week's evidence adds up to in Hematology. First, mitapivat now has randomised evidence for raising haemoglobin in sickle cell disease, but it did not significantly reduce pain crises, so its disease-modifying role remains unproven. Second, real-world data on iptacopan in paroxysmal nocturnal hemoglobinuria and long-term emicizumab surveillance both point to durable efficacy and stable safety, with long-term infection risk for iptacopan still to be characterised. Third, in polycythemia vera, first-line ruxolitinib failed its primary endpoint while showing symptomatic benefits, and faster ropeginterferon titration looks more effective in pooled non-randomised data awaiting prospective confirmation. Fourth, post-transplant cyclophosphamide appears to narrow donor differences, but related donors carry a small, germline-driven risk of donor-derived neoplasms, adding weight to germline screening. And fifth, daratumumab's infection risk clusters in the first three months, a timing signal that observational prevention strategies have yet to exploit.
That's your roundup for This Week in Hematology. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.
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