This Week in Hematology — Jul 8, 2026

Welcome to This Week in Hematology. This week we are covering eight notable papers spanning advances in cellular immunotherapies, optimization of plasma cell disorder regimens, and novel risk stratification and supportive care strategies in hematologic conditions. Let's dive in.

We begin this week with major developments in immunotherapy and chimeric antigen receptor, or CAR, T-cell therapies. In the British Journal of Haematology, Villeneuve and colleagues published a population-based retrospective cohort study evaluating the real-world health outcomes of patients with relapsed or refractory aggressive B-cell lymphoma treated with publicly funded CAR T-cell therapy in Ontario, Canada, compared to historical controls [8]. The study analyzed three hundred and fourteen patients who received commercially available CAR T-cells between 2019 and 2023, comparing them to one hundred and six historical controls treated with the standard of care between 2013 and 2018, before public funding was available. Using inverse probability of treatment weighting to balance patient characteristics such as age, performance status, and prior lines of therapy, the researchers found that CAR T-cell therapy roughly halved the risk of death compared to historical therapies. The median overall survival was fifteen point one months in the CAR T-cell group compared to just four point eight months in the historical control group. This robust real-world evidence confirms that the dramatic survival benefits observed in clinical trials of CAR T-cell therapy translate successfully into routine clinical practice, despite the high costs and toxicities associated with these advanced cellular therapies. While CAR T-cell therapy has established a firm foothold in aggressive lymphomas, researchers are actively seeking ways to overcome resistance and antigen escape in other hematologic malignancies, such as multiple myeloma. In the journal Blood, Mailankody and colleagues investigated a novel strategy to combat antigen heterogeneity by concurrently administering two different CAR T-cell products [2]. In a phase one dose-escalation trial, they evaluated the safety and efficacy of targeting both B-cell maturation antigen, or BCMA, and G-protein coupled receptor class C group 5 member D, or GPRC5D. They treated fifteen heavily pre-treated patients with relapsed or refractory multiple myeloma across three dose levels. Six patients received the BCMA-targeting CAR T-cell therapy, known as MCARH125, alone, while nine patients received a concurrent co-infusion of MCARH125 and the GPRC5D-targeting CAR T-cell therapy, MCARH109. Safety-wise, one patient in each cohort developed immune effector cell-associated hemophagocytic syndrome, but there were no instances of grade three or higher cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. The co-infusion cohort demonstrated an encouraging overall response rate of seventy-eight percent, with a median progression-free survival of eighteen point two months. However, the correlative analyses revealed a fascinating and cautionary biological phenomenon. The researchers demonstrated for the first time that the expansion of one CAR T-cell population can actively limit the expansion of the second population. Specifically, patients who received the dual co-infusion had significantly less BCMA-CAR T-cell expansion than those who received the BCMA-CAR T-cell therapy alone, despite receiving identical doses of the BCMA-directed cells. Furthermore, antigen loss remained a key mechanism of resistance even with dual-antigen targeting. These findings suggest that simply combining two CAR T-cell products may introduce competitive dynamics that limit the efficacy of one or both therapies, a crucial consideration for the design of future multi-targeted cellular immunotherapies. The rapid evolution of these cellular and targeted immunotherapies is also reshaping the management of adult acute lymphoblastic leukemia, or ALL. Writing in Blood Cancer Journal, Jabbour and Kantarjian provide a comprehensive review of how recent therapeutic advances are being incorporated into frontline and relapsed treatment strategies [6]. The authors highlight how the integration of the bispecific T-cell engager blinatumomab has demonstrated a significant survival advantage in patients with both newly diagnosed Philadelphia chromosome-positive and Philadelphia chromosome-negative ALL. Similarly, the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin has been safely integrated into frontline treatment backbones for both younger and older patients. Meanwhile, CAR T-cell therapies are delivering durable remissions, especially in patients with a lower disease burden. The authors discuss how the current research focus is shifting toward treatment optimization, specifically by replacing traditional, highly toxic chemotherapy regimens with these targeted immunotherapies. The ultimate goal of these novel combinations is to reduce acute and long-term toxicities, minimize the need for allogeneic stem cell transplantation, and shorten the overall intensity and duration of therapy while simultaneously improving long-term survival outcomes.

Turning to plasma cell disorders, we examine a highly anticipated clinical debate regarding the optimal induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma. In the British Journal of Haematology, Marcoux and colleagues present a large, single-center retrospective analysis comparing carfilzomib, lenalidomide, and dexamethasone, known as the KRd regimen, to bortezomib, lenalidomide, and dexamethasone, known as the VRd regimen [3]. The study evaluated eleven hundred and twenty-nine patients who received either KRd or VRd induction prior to upfront autologous hematopoietic stem cell transplantation. Notably, patients in the KRd group more frequently had high-risk cytogenetics and advanced disease stages. Despite this higher-risk profile, patients treated with KRd achieved significantly deeper responses prior to transplant. The pre-transplant complete response and very good partial response rates were seventy-one percent with KRd compared to sixty-one percent with VRd. KRd also led to a higher rate of pre-transplant measurable residual disease negativity, at forty-nine percent versus forty-two percent. After a median follow-up of nearly thirty-nine months, the median progression-free survival was sixty-two point two months in the KRd group compared to forty-eight point seven months in the VRd group, representing a twenty-six percent reduction in the risk of disease progression or death. However, this superior progression-free survival did not translate into a statistically significant difference in overall survival. Multivariable analysis confirmed that the progression-free survival benefit of KRd was most pronounced in younger, male, and standard-risk patients, as well as those with fewer comorbidities. For practicing clinicians, these findings suggest that while KRd provides deeper responses and longer disease control, the choice between these regimens should be tailored to individual patient risk profiles and tolerability. In another key update on plasma cell disorders, the American Journal of Hematology published a comprehensive 2026 clinical update on the diagnosis, risk stratification, and management of POEMS syndrome by Dispenzieri [7]. POEMS syndrome is a rare, life-threatening multi-system disorder driven by an underlying clonal plasma cell neoplasm. The author outlines the diagnostic criteria, which require at least three major criteria, including polyneuropathy and a clonal plasma cell disorder, plus at least one minor criterion such as organomegaly, endocrinopathy, skin changes, papilledema, extravascular volume overload, or thrombocytosis. Because the precise molecular pathogenesis remains poorly understood, risk stratification relies heavily on clinical phenotypes, with poor prognostic markers including low serum albumin, advanced age, pleural effusion, pulmonary hypertension, and reduced kidney function. The review details the risk-adapted therapeutic approach: patients with a single dominant osteosclerotic plasmacytoma should receive localized radiation therapy as first-line treatment. In contrast, patients with diffuse sclerotic lesions or disseminated bone marrow involvement require systemic therapy. While corticosteroids offer temporary relief, the mainstays of systemic treatment are alkylating agents and lenalidomide, either as low-dose conventional therapy or as high-dose conditioning followed by autologous stem cell transplantation. The author notes that while proteasome inhibitors like bortezomib and immunomodulators like thalidomide are highly active, clinicians must carefully weigh their benefits against the substantial risk of exacerbating the patient's pre-existing peripheral neuropathy. Additionally, emerging data from case series suggest that daratumumab-based combinations represent a highly promising future avenue for these patients.

We next transition to myeloid malignancies and clonal hematologic disorders, where novel diagnostic markers and combination therapies are improving patient outcomes. In the journal Blood, Lane and colleagues reported the results of a phase two clinical trial evaluating a novel triplet regimen for patients with blastic plasmacytoid dendritic cell neoplasm, or BPDCN [1]. BPDCN is an aggressive, rare hematologic malignancy characterized by high expression of CD123 and a strong dependence on the anti-apoptotic protein BCL2. While the CD123-directed toxin tagraxofusp is the only approved therapy, resistance often develops. To address this, the researchers evaluated a combination of tagraxofusp, azacitidine, and venetoclax in twenty-seven patients, including sixteen who were previously untreated and eleven with relapsed or refractory disease. The triplet regimen demonstrated remarkable efficacy, achieving a composite complete remission rate of eighty-eight percent in the previously untreated cohort and sixty-four percent in the relapsed or refractory cohort. The median duration of response and median overall survival were not reached in the frontline group, with a two-year overall survival rate of sixty-five percent. In the relapsed or refractory group, the median overall survival was eight point four months. Importantly, this highly active regimen served as an effective bridge to definitive therapy, allowing sixty-three percent of frontline patients and fifty-five percent of relapsed or refractory patients to proceed to an allogeneic stem cell transplantation while in remission. Safety-wise, capillary leak syndrome, which is a known and potentially severe complication of tagraxofusp, occurred in fifteen percent of patients, but the majority of cases were mild to moderate and manageable. These findings support the tagraxofusp, azacitidine, and venetoclax triplet as a highly active and tolerable new therapeutic option for this difficult-to-treat malignancy. In another significant study addressing clonal hematologic disorders, Wagner-Ballon and colleagues published a prospective observational study in the American Journal of Hematology investigating the clinical significance of PNH Type II neutrophils in patients with paroxysmal nocturnal hemoglobinuria [5]. PNH is characterized by the clonal expansion of hematopoietic stem cells deficient in GPI-anchored proteins. While Type I cells are normal and Type III cells completely lack GPI-anchored proteins, Type II cells exhibit a partial deficiency. The clinical relevance of these Type II cells has historically been unclear. The researchers analyzed a French nationwide cohort of three hundred and fifty-five patients with a PNH clone of at least one percent on neutrophils. Among patients with a major PNH clone of fifty percent or greater, they identified that a threshold of three percent or more of Type II neutrophils distinguished a distinct clinical subgroup. Patients in this 'high Type II' group experienced less frequent hemolysis but had a significantly higher frequency of thrombotic events both at diagnosis and during long-term follow-up. Multivariable analysis confirmed that a relative percentage of Type II neutrophils of three percent or greater was independently associated with a higher risk of thrombosis. Even in patients with smaller PNH clones between one and fifty percent, thrombotic events during follow-up occurred exclusively in the 'high Type II' group. Over long-term follow-up, the relative percentage of Type II neutrophils remained highly stable, regardless of changes in the overall clone size. The authors conclude that the relative percentage of Type II neutrophils is a reliable, stable predictor of thrombotic risk, suggesting that clinicians should consider earlier initiation of anticomplement therapy in patients who meet this high-risk threshold, even if their overall clone size is relatively small.

Finally, we turn to a common and challenging supportive care issue in oncology: chemotherapy-induced thrombocytopenia, or CIT. In a 'How I Treat' article in Blood, Al-Samkari and Soff provide a practical, evidence-based guide on using thrombopoietin receptor agonists, or TPO-RAs, to manage this complication [4]. CIT frequently leads to major bleeding events and forces clinicians to reduce chemotherapy doses or delay treatment cycles, which can compromise relative dose intensity and worsen oncologic outcomes. The authors emphasize that proper management requires distinguishing between the two distinct clinical subtypes of CIT: persistent CIT, where platelet counts fail to recover before the next planned chemotherapy cycle, and nadir-type CIT, which is characterized by a transient drop in platelet counts that recovers spontaneously. They note that traditional strategies, such as platelet transfusions and antifibrinolytics, have highly limited roles in this setting. Instead, the authors advocate for the appropriate use of TPO-RAs, such as romiplostim and avatrombopag, which have demonstrated efficacy in large phase three clinical trials. Using illustrative clinical cases, they outline detailed strategies for proper patient selection, starting doses, weekly titration, and safety monitoring. By integrating TPO-RA support into clinical practice, hematologists can help oncology colleagues maintain chemotherapy scheduling and dosing, ultimately improving overall patient outcomes.

If you only have time for one paper this week, make it the phase two trial of tagraxofusp, azacitidine, and venetoclax in blastic plasmacytoid dendritic cell neoplasm by Lane and colleagues in Blood [1]. This study provides a highly active, practice-changing triplet regimen that achieves remarkable remission rates and successfully bridges a high proportion of patients with this aggressive orphan disease to curative stem cell transplantation.

Here are the key takeaways from this week in Hematology. First, a triplet regimen combining tagraxofusp, azacitidine, and venetoclax produces high complete remission rates in both treatment-naive and relapsed blastic plasmacytoid dendritic cell neoplasm, serving as an effective bridge to allogeneic stem cell transplantation. Second, in transplant-eligible newly diagnosed multiple myeloma, KRd induction achieves deeper pre-transplant responses and significantly improves progression-free survival compared to VRd, though it does not demonstrate a clear overall survival benefit. Third, real-world population data confirms that commercially available CAR T-cell therapy roughly halves the risk of death for patients with relapsed or refractory aggressive B-cell lymphoma compared to historical standards of care. Fourth, when designing or administering dual-targeting CAR T-cell therapies, clinicians must be aware that the in vivo expansion of one CAR T-cell population can actively suppress the expansion of the second population. And finally, in patients with paroxysmal nocturnal hemoglobinuria, a relative proportion of Type II neutrophils of three percent or greater is a stable marker that independently predicts a higher risk of thrombosis, potentially warranting earlier initiation of anticomplement therapy.

That's your roundup for This Week in Hematology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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