Evolving Treatment Paradigms in hematologic malignancies: Real-world Insights into Bispecific Antibodies and BTK Inhibitors
Published: 2026/01/14 02:33:13
The landscape of treating blood cancers like multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) is undergoing a rapid transformation. New targeted therapies are increasingly available, even in community oncology settings. Recent analyses,discussed by Ira Zackon,MD,senior medical director at Ontada,during the 67th american Society of Hematology (ASH) Annual Meeting and Exposition,shed light on the adoption,patient characteristics,and treatment approaches associated with these novel agents. This article delves into these findings, exploring the growing use of bispecific antibodies in myeloma and the challenges surrounding long-term use of Bruton tyrosine kinase (BTK) inhibitors in CLL, and what these real-world observations mean for patient care.
Rapid Adoption of Bispecific Antibodies in Multiple Myeloma
Bispecific antibodies represent a notable advancement in the treatment of relapsed or refractory multiple myeloma. These innovative therapies work by together binding to both the myeloma cells and the patient’s immune cells, effectively bridging the gap and directing the immune system to destroy the cancer. A retrospective study examined the uptake of these antibodies in a real-world setting, analyzing data from The US Oncology Network between October 2022 and July 20251.
The results are encouraging. In 2022, only 5% of patients with myeloma who were eligible for bispecific therapy (having received at least five prior lines of treatment) received one. However,this number climbed dramatically to 39% in 2023,61% in 2024,and reached 73% by mid-2025. This rapid increase demonstrates a swift integration of these therapies into clinical practice.
Dr. Zackon emphasizes the importance of this trend, stating that broad access to these therapies is crucial for maximizing patient benefit. Delivering these treatments in community oncology settings, alongside academic and hospital-based centers, is key to achieving this goal.
Patient Characteristics and Bispecific Antibody Selection
While the uptake of bispecific antibodies is promising, the study also revealed some differences between real-world patients and those enrolled in clinical trials. Real-world patients tended to be older, with a median age of 72 years compared to frequently enough under 70 in clinical trials. Moreover, patients receiving bispecific antibodies generally had better performance status – meaning they were more physically fit and able to carry out daily activities – than those who did not (approximately 20% had an Eastern Cooperative Oncology Group score of 2 or greater, compared to 30% in the non-bispecific group).
These findings highlight the importance of considering individual patient characteristics when making treatment decisions. Factors beyond the disease itself, such as age, overall health, and logistical considerations (caregiver support, transportation) can all influence a patient’s ability to receive and tolerate these therapies.
Discontinuation Rates and the Future of BTK Inhibitor Therapy in CLL
Chronic lymphocytic leukemia (CLL) is another blood cancer benefiting from targeted therapies, particularly BTK inhibitors. These drugs block a protein crucial for CLL cell survival and proliferation. However, a study analyzing data from the CLL17 trial (NCT04608318) revealed a concerning trend: high discontinuation rates for even second-generation BTK inhibitors in real-world practice2.
The study, encompassing 584 patients receiving frist-line covalent BTK inhibitors (ibrutinib, acalabrutinib, or zanubrutinib) between November 2019 and July 2023, found that approximately two-thirds of patients discontinued treatment during the study period. Discontinuation rates were 40% for acalabrutinib, 50% for zanubrutinib, and 56% for ibrutinib. The primary reason for discontinuation was adverse events (AEs), suggesting that long-term tolerability remains a significant challenge.
While second-generation BTK inhibitors were designed to have improved safety profiles (particularly regarding cardiovascular events like atrial fibrillation and hypertension), the study showed that discontinuation rates due to aes remained substantial. This raises questions about the feasibility of indefinite treatment with these agents for many patients.
Time-Limited Therapy and Combination Approaches
The high discontinuation rates observed with continuous BTK inhibitor therapy are prompting a re-evaluation of treatment strategies. Time-limited approaches, such as the combination of venetoclax (a BCL-2 inhibitor) and obinutuzumab (an anti-CD20 monoclonal antibody), are gaining traction.
The potential benefits of time-limited therapy include a shorter duration of treatment, reduced exposure to side effects, and possibly lower treatment costs.Furthermore, combinations like acalabrutinib and venetoclax are being explored to enhance efficacy and potentially allow for treatment-free intervals.
Dr. zackon notes that the use of minimal residual disease (MRD) measurements – assessing the level of cancer cells remaining after treatment – may play a crucial role in guiding treatment duration. Achieving a deep MRD response could potentially identify patients who may benefit from stopping therapy, while those with persistent MRD may require continued treatment.
The Role of Real-world Data in Shaping Oncology Care
These findings underscore the importance of real-world data in complementing clinical trial results. Clinical trials, while essential for establishing efficacy and safety, often enroll a highly selected patient population. Real-world studies, like those conducted using data from The US Oncology Network, provide a more representative picture of how these therapies perform in diverse patient populations with varying comorbidities and health statuses.
The insights gained from these studies are helping to refine treatment algorithms, personalize care, and ultimately improve outcomes for patients with hematologic malignancies. Ongoing research and clinical trials will continue to shape the future of treatment,with a focus on optimizing both efficacy and tolerability.
Key Takeaways:
* Bispecific antibodies are being rapidly adopted in the treatment of relapsed/refractory multiple myeloma.
* Real-world myeloma patients tend to be older than those in clinical trials, highlighting the need for individualized treatment approaches.
* Discontinuation rates for BTK inhibitors in CLL remain high due to adverse events, raising questions about the sustainability of continuous therapy.
* Time-limited therapies and combination approaches are emerging as promising alternatives for CLL treatment.
* Real-world data is crucial for understanding how novel therapies perform in diverse patient populations and informing clinical practice.
- Whitesell M, Su Z, Herms L, Espirito J, Paulus J, Zackon I. Evolving real-world uptake and patient characteristics of bispecific antibodies in relapsed/refractory multiple myeloma: insights from a US community oncology network. Presented at: 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; Orlando, FL. Abstract 15172.
- Al-Sawaf O,Stumpf J,Zhang C,et al. Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: results from the randomized CLL17 trial. Presented at: 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; orlando, FL. Abstract 2071.
- Ibrutinib monotherapy versus fixed-duration venetoclax plus obinutuzumab versus fixed-duration ibrutinib plus venetoclax in patients with previously untreated chronic lymphocytic leukaemia (CLL) (CLL17). ClinicalTrials.gov. Updated December 31, 2024. Accessed December 17, 2025. https://clinicaltrials.gov/study/NCT04608318
