The 2026 American Society of Clinical Oncology (ASCO) conference, a cornerstone event for oncological advancements, has concluded, leaving a significant imprint on the landscape of blood cancer research and treatment. This year’s gathering saw a wealth of critical data readouts, spanning common hematological malignancies like chronic lymphocytic leukemia (CLL) and multiple myeloma to rarer, yet equally devastating, conditions such as myelofibrosis. Pharmaceutical Technology has meticulously reviewed the proceedings, highlighting the most impactful findings that are poised to reshape patient care and therapeutic strategies in the coming years. The discussions and presentations at ASCO 2026 underscored a dynamic period of innovation, characterized by the refinement of existing therapies and the emergence of novel treatment paradigms.
BeOne’s Brukinsa Demonstrates Sustained Long-Term Control in Chronic Lymphocytic Leukemia
A significant focal point of ASCO 2026 was the presentation of extended follow-up data for BeOne’s Bruton’s tyrosine kinase (BTK) inhibitor, Brukinsa (zanubrutinib). The Phase III SEQUOIA study (NCT03336333), which directly compared Brukinsa against the standard of care (SoC) regimen of bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), provided compelling evidence of Brukinsa’s durable efficacy.
After an impressive 78 months of follow-up, patients treated with Brukinsa achieved a progression-free survival (PFS) rate of 71.8%. This figure stands in stark contrast to the 31% PFS rate observed in the BR arm, indicating a more than twofold improvement in disease control for Brukinsa. The benefits were even more pronounced in a specific patient subgroup, those with mutations in gene segments associated with B-cell antibody production. In this population, the PFS rate with Brukinsa reached 81.8% at 78 months, compared to 45.1% in the BR arm. These findings are particularly noteworthy as they demonstrate sustained efficacy over a considerable period, addressing the chronic nature of CLL and the need for long-term disease management.
Beyond PFS, trends favoring Brukinsa were also observed in the time to next treatment, suggesting that patients on Brukinsa require fewer subsequent therapies. The drug’s safety profile remained consistent with previously reported data, a crucial factor for chronic treatments where tolerability is paramount.
Furthermore, BeOne presented a novel real-world analysis that positioned Brukinsa as a superior option compared to other BTK inhibitors, specifically AbbVie and Johnson & Johnson’s Imbruvica (ibrutinib) and AstraZeneca’s Calquence (acalabrutinib). This analysis indicated that Brukinsa could significantly reduce a patient’s risk of death, the need to advance to a subsequent line of therapy, or treatment discontinuation. These positive outcomes were observed across various age subgroups, further solidifying Brukinsa’s potential as a best-in-class BTK inhibitor.
Dr. Amit Agarwal, BeOne’s Chief Medical Officer for Hematology, emphasized the significance of these long-term findings. "The true measure of a therapy’s benefit lies in how it performs over the long arc of treatment, especially given the often chronic nature of CLL," Dr. Agarwal stated. "Our data at ASCO demonstrate that Brukinsa continues to deliver sustained disease control, which can instill confidence in physicians and patients to stay the course. Robust, real-world analyses reinforce its role as a best-in-class BTK inhibitor, with data favoring Brukinsa over other BTK inhibitors across several efficacy and safety endpoints." The implications of these findings are substantial, potentially shifting treatment guidelines and offering a more durable and less burdensome treatment option for newly diagnosed CLL patients.
Karyopharm’s Xpovio Shows Promise in Combination Therapy for Myelofibrosis
In the challenging realm of myelofibrosis, a rare and aggressive bone marrow cancer, Karyopharm presented data at ASCO 2026 suggesting that its exportin-1 inhibitor, Xpovio (selinexor), could offer an additive benefit when combined with standard of care (SoC) Janus kinase (JAK) inhibitors, such as Pfizer’s Jakafi (ruxolitinib), for symptomatic patients requiring treatment.
The topline results from the Phase III SENTRY trial (NCT04562389), which evaluated the combination of Xpovio and Jakafi in JAK inhibitor-naïve myelofibrosis patients, met one of its co-primary endpoints. Specifically, 50% of patients receiving the Xpovio-Jakafi combination experienced a 35% or greater reduction in spleen volume, a critical indicator of disease burden in myelofibrosis. This achievement significantly outperformed the 28% spleen volume reduction observed in patients treated with Jakafi monotherapy. Spleen enlargement is a common and debilitating symptom of myelofibrosis, contributing to pain, early satiety, and fatigue. A significant reduction in spleen size often correlates with improved quality of life.
Furthermore, researchers noted an early overall survival (OS) signal favoring the combination therapy over Jakafi alone (p=0.0222). While this signal requires further maturation and will be closely monitored as the trial progresses to completion, it represents a potentially groundbreaking development in a disease with limited curative options. Karyopharm has committed to following this OS signal to maturity to provide a more definitive assessment of its long-term impact.
However, the trial did not meet its second key primary endpoint, which assessed symptom response from baseline to week 24. Patients receiving the Xpovio-Jakafi combination achieved an improvement of 10.86 points in symptom scores, a result that narrowly missed demonstrating superiority over the 9.89-point improvement seen in the Jakafi monotherapy group. This endpoint is crucial as it directly relates to patient-reported outcomes and the alleviation of debilitating symptoms.
Treatment discontinuation rates were also slightly higher in the Xpovio-Jakafi arm, with 14.5% of patients discontinuing the study compared to 8.6% in the Jakafi-only arm. This observation warrants careful consideration regarding the overall tolerability of the combination in a real-world setting, although it is important to note that these figures represent study discontinuations, not necessarily treatment intolerances.
Dr. Andrew Kuykendall of Moffitt Cancer Center, commenting on the SENTRY trial results via LinkedIn, expressed intrigue regarding the early survival benefit associated with the Selinexor-ruxolitinib combination. He highlighted the need for further investigation as more data becomes available, suggesting that this finding could represent a significant advancement if confirmed. The potential for Xpovio to enhance the efficacy of JAK inhibitors in myelofibrosis, particularly in terms of survival, could offer a much-needed new avenue for patients who currently have limited therapeutic choices beyond existing therapies.
Cellectar Biosciences’ Iopofosine I 131 Achieves Success in Waldenström Macroglobulinemia
In another notable advancement for rare blood cancers, Cellectar Biosciences announced a significant victory for its radiopharmaceutical and phospholipid-drug conjugate (PDC), iopofosine I 131. The drug has posted a successful Phase IIb outcome in relapsed or refractory (R/R) Waldenström macroglobulinemia (WM), prompting Cellectar to plan for an accelerated US approval filing.
The CLOVER WaM study (NCT02952508) enrolled R/R patients with symptomatic WM who had received at least two prior lines of therapy. In this trial, patients were administered the radiopharmaceutical iopofosine I 131 immediately following treatment with a Bruton’s tyrosine kinase (BTK) inhibitor. This sequential approach targets a critical unmet need, as patients often experience limited response and rapid disease progression after BTK inhibitor therapy.
The results were highly encouraging, with an overall response rate (ORR) of 87.5% observed among the 24 enrolled patients. Of these, a remarkable 79.2% achieved a partial response (PR) or better, indicating a substantial positive impact on their disease. The median duration of response (DOR) was 16 months, with an impressive 20% of patients maintaining a DOR of 30 months or longer. These long-lasting responses are particularly significant in a relapsed/refractory setting where treatment options are often limited and efficacy is typically shorter-lived.
Patients generally tolerated iopofosine I 131 well. The only treatment-related side effect to reach Grade 3 or higher was cytopenia, a common side effect associated with treatments affecting the bone marrow. The favorable safety profile, coupled with the robust efficacy, positions iopofosine I 131 as a promising new therapeutic agent for this rare lymphoma subtype.
To further confirm these findings and support regulatory submissions, Cellectar is initiating a confirmatory Phase III study of iopofosine I 131 in WM, which is expected to commence in Q4 2026.
Jarrod Longcor, Cellectar’s Chief Operating Officer, highlighted the unmet need in the post-BTK inhibitor setting. "Patients with post-BTK inhibitor disease often experience limited response and rapid disease progression after BTK inhibitor discontinuation, representing a notable unmet need," Longcor stated. "These outcomes give us even greater confidence in the potential of iopofosine to be effective in an earlier line setting, as will be evaluated in the planned Phase 3 confirmatory study." The success of iopofosine I 131 in WM signifies a potential paradigm shift in treating patients who have exhausted or progressed on existing therapies, offering hope for improved outcomes and extended disease control.
AL Amyloidosis Sees Promising Developments Amidst Mixed Trial Outcomes
ASCO 2026 also brought significant updates in the treatment of light chain (AL) amyloidosis, a rare and serious condition characterized by the deposition of misfolded light chains in organs. Both Regeneron and AstraZeneca presented data from their late-stage development programs, offering a glimpse into the evolving therapeutic landscape.
AstraZeneca’s anti-fibril therapy, anselamimab, faced a setback as it failed to meet its primary endpoint in a Phase III trial within the global CARES program. However, the therapy did demonstrate statistically significant benefits over placebo for adults with advanced kappa AL amyloidosis when used as a frontline therapy in addition to standard of care. This nuanced outcome suggests that while anselamimab may not be a universal solution for all AL amyloidosis patients, it could play a role in specific subgroups, particularly those with kappa light chain involvement. Further analysis of the trial data will be crucial to understand the precise patient populations that might benefit most from this approach.
In contrast, Regeneron’s BCMA-CD3-directed bispecific antibody, linvoseltamab, being explored in the Phase I/II LINKER AL-2 trial (NCT06292780), showed promising early efficacy and a manageable safety profile. In the study of 20 patients with R/R AL amyloidosis, none experienced dose-limiting toxicity or immune effector cell-associated neurotoxicity syndrome (ICANS). While one patient died due to a ventricular fibrillation event, the investigator deemed it unrelated to the study drug.
The early efficacy data for linvoseltamab was particularly encouraging. A remarkable 100% of patients receiving the 80mg dose and 92.3% of those receiving the 240mg dose achieved a hematologic objective response (hOR). These high response rates suggest that targeting BCMA with a bispecific antibody could be a potent strategy for inducing deep hematologic responses in AL amyloidosis.
Jill Condello, Senior VP of Medical Strategy at OPEN Health, commented on these updates via LinkedIn, noting that the developments from AstraZeneca and Regeneron "pointed to new, biology-driven approaches in a space that has had very few options beyond standard plasma-cell-directed regimens." Her observation highlights the critical need for innovative treatments beyond the established plasma-cell-targeting therapies.
Currently, Johnson & Johnson’s Darzalex Faspro (daratumumab and hyaluronidase-fihj) stands as the only drug specifically approved for AL amyloidosis, underscoring the significant unmet need for novel therapeutic options. The data presented at ASCO 2026, while mixed, signals progress in developing new strategies that could improve patient outcomes and address the limitations of existing treatments. The continued exploration of novel targets and mechanisms of action is vital for advancing the care of patients with this debilitating disease.
The collective findings from ASCO 2026 paint a picture of significant progress and ongoing innovation in the field of hematological malignancies. From extended long-term data solidifying the role of existing therapies to promising early results for novel agents and combinations, the conference has provided valuable insights that will undoubtedly influence clinical practice and drive future research. The focus on both common and rare blood cancers at this pivotal event demonstrates a commitment to addressing the diverse needs of patients battling these complex diseases.
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