Operationalizing Bispecific Antibodies Across Academic and Community Oncology Centers in Hematologic Malignancies

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As oncology care continues to transition from chemotherapy, targeted treatments have taken center stage, in turn providing more effective and less toxic treatment options for patients. In the world of hematology, novel therapies have looked to harness the body’s own immune system to counteract cancer’s immunological invisibility, thus making hematologic malignancies susceptible to cellular therapies. Bispecific antibodies (BsAbs) have recently emerged as a readily available treatment option, with 6 products gaining FDA approval for either lymphoma or multiple myeloma (MM) in the past 2 years.^1-5

Although the initial approval of these agents is a landmark celebration for patients, the inability to operationalize novel treatment to expand access to those who do not live in a geographically favorable location near an academic medical center remains an insurmountable challenge. To counteract and bring awareness to these challenges, an interdisciplinary discussion involving nurse practitioners, pharmacists, and physicians was conducted at the 2024 National Community Oncology Dispensing Association (NCODA) International Spring Forum in Dallas, Texas, to address the disparity in availability and use of BsAbs across the continuum of care in US health care.

Historically, patients with MM have been dichotomized by their transplant eligibility, as it plays a large role in the selection of treatment regimens from initial diagnosis. With the ascension of chimeric antigen receptor (CAR) T-cell therapy in MM to as early as the second line, this creates a need for a new stratification when determining treatment eligibility. Although CAR T-cell therapy is often considered more tolerable compared with transplant, the patients who are ineligible for both CAR T-cell therapy and autologous stem cell transplant due to fitness are viewed as the patient population primed to receive the greatest benefit from BsAb therapy.

Patients suitable for BsAb therapy are usually heavily pretreated, unfit, and older adults. Given that most of these patients are naive to CAR T-cell therapy, patient education on novel toxicities such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) is a vital component to treatment success.^6-9

During the discussion at the NCODA International Spring Forum, the consensus was that a multidisciplinary approach to management of patients receiving BsAbs is the best course of action to ensure success. Specifically, patient education led by pharmacists helps to provide a holistic view of all components of treatment. The panelists agreed that pharmacist-led education ensured a thorough understanding of treatment schedule, toxicities, and supportive care associated with these novel therapies.

When it comes to patient monitoring, despite the requirements to monitor patients continuously for 48 hours following each step-up dose, institutions around the country are looking for ways to transition this process to an entirely outpatient setting. Oncology care is moving in a direction to avoid hospital admissions. To align with this, progressive academic medical centers have implemented on-body temperature and vital sign monitoring with instantaneous reporting to health care providers for patients receiving BsAbs. With temperature and blood pressure monitoring being the most crucial components of early detection of CRS, the ability to monitor these with on-body technology at home provides patients with the convenience of being able to initiate these therapies in the outpatient setting. Furthermore, for those initiating in the inpatient setting, condensed dose ramp-up affords the patient less time in the hospital prior to maintenance therapy being initiated in the outpatient setting.

It is expected that as these BsAbs continue to be studied, they will become available for patients as treatment options for earlier lines of therapy. Given that these agents are administered either weekly or biweekly until unacceptable toxicity or progression, administration at an academic medical center can be difficult for those patients traveling far distances from rural areas. Transitioning care to allow for patients to receive these therapies close to home is essential in supporting the expansion of use across a spectrum of hematologic malignancies. Community oncology care centers do not have the same infrastructure that academic medical centers benefit from, and, therefore, the understanding of the scope of use for these agents plays a vital role in facilitating transfer of care.

During the NCODA panel discussion, representatives of sites of care discussed how clear communication and the use of state oncology organizations provide the most effective strategies when identifying needs and filling voids in education and operational abilities to allow more patients to transition these therapies to tertiary care centers. Proactive acceleration of prior authorization of both BsAbs and supportive care infusions associated with treatment is essential in preventing lapses in care, which ensures patients do not need to reramp their treatment in the inpatient setting.

Operational challenges with BsAbs are not unique to the tertiary care network, as all oncology care centers face various operational challenges when novel therapies are approved and in need of use imminently. From addition to formulary to order set and staff education development, institutions looking to use BsAbs must ensure all members of the care team are educated and equipped to carry out use of these agents. The panelists partaking in this discussion were able to speak from experience where implementation of these agents’ identified gaps within the system led to delays in administration. Swift collaboration to develop protocols and guidelines, as well as bridging these gaps, provide insight into how all care centers looking to operationalize BsAbs can avoid the same shortfalls. Some of these gaps included ensuring both inpatient and outpatient authorization for use, standardization of toxicity management through extensive protocol development, and formalized education for all staff involved in any aspect of care for patients initiating treatment with BsAbs.

Overall, one cannot help but be happy with the extensive treatment options now available for patients with hematologic malignancies. Chemotherapy-free treatment was once a dream, but it is now becoming a reality with the introduction of cellular therapies aimed at eliminating the need for toxic multiagent regimens. Although we are still far from achieving this dream in its entirety, it does not matter how effective novel therapies are if they are not widely available across the United States for eligible patients.

Academic medical centers are poised to be the pillar of care for these treatments; however, collaboration will be key to ensuring no patient goes without the opportunity to be treated with the best therapy available. Panel discussions that bring all stakeholders together, such as the one held at the 2024 NCODA International Spring Forum, are an important step in encouraging this collaboration, with the mutual goal in mind of ultimately creating a health care system where patients are placed at the center of care.

References

1. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478

2. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9

3. Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232-2244. doi:10.1056/NEJMoa2204591

4. Einsele H, Borghaei H, Orlowski RZ, et al. The BiTE (bispecific T-cell engager) platform: development and future potential of a targeted immuno-oncology therapy across tumor types. Cancer. 2020;126(14):3192-3201. doi:10.1002/cncr.32909

5. Zhou S, Liu M, Ren F, Meng X, Yu J. The landscape of bispecific T cell engager in cancer treatment. Biomark Res. 2021;9(1):38. doi:10.1186/s40364-021-00294-9

6. Cosenza M, Sacchi S, Pozzi S. Cytokine release syndrome associated with T-cell-based therapies for hematological malignancies: pathophysiology, clinical presentation, and treatment. Int J Mol Sci. 2021;22(14):7652. doi:10.3390/ijms22147652

7. Morris EC, Neelapu SS, Giavridis T, Sadelain M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol. 2022;22(2):85-96. doi:10.1038/s41577-021-00547-6

8. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758

9. Kowalski A, Lykon J, Diamond B, et al. Emerging strategies for the prevention of immune toxicities associated with T cell-engaging cancer therapies. Blood Cancer Discov. 2024;5(2):90-94. doi:10.1158/2643-3230.Bcd-23-0228