Zahra Mahmoudjafari Introduces The Bispecifics Network

The emergence of bispecific antibodies has meaningfully reshaped the treatment landscape across hematologic malignancies and beyond. As these agents have moved from early investigation into broader clinical practice, questions around operationalization, sequencing, and long-term immune management have come to the forefront. The following discussion explores the evolution of bispecific therapies, the infrastructure required to deliver them safely and effectively, and the outstanding questions that will define their role in the years ahead.

Pharmacy Times spoke with Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, a clinical pharmacy manager in the blood and marrow transplant program in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Cancer Center in Kansas City, about The Bispecifics Network—an interactive resource for clinics to learn about operationalizing bispecifics in cancer care.

Pharmacy Times: We’ve seen a massive surge in bispecific approvals recently, moving from rare exceptions to a primary pillar of oncology and beyond. In your view, what was the 'tipping point' that made bispecifics a viable, off-the-shelf alternative to personalized therapies like CAR-T?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: There wasn't necessarily a single moment—more of a convergence of factors. Early on, bispecifics were very exciting, but the concern was how to operationalize these new and developing agents in a more standardized way. What changed is that we're starting to see consistent and meaningful efficacy now that we've had bispecifics over a period of time. They also came with a unique toxicity profile that was unfamiliar to some treatment teams who may not have dealt with cytokine release syndrome or neurotoxicity. With step-up dosing strategies, CRS has become more manageable, and suddenly these therapies are something you have to operationalize, not just study.

At the same time, the contrast with CAR-T is becoming much clearer. CAR-T is incredibly powerful and has been on the market much longer—however, it remains resource-intensive and not always accessible in a timely fashion. Bispecifics have filled that gap. They're off-the-shelf, readily available, and scalable across more sites of care when the appropriate infrastructure is in place. The tipping point, for me, was when bispecifics stopped being viewed as a bridge or an alternative and began being seen as a foundational option in their own right.

Pharmacy Times: Bispecifics are often described as 'molecular matchmakers' between immune cells and cancer. Beyond just T-cell engagers, what are the most exciting 'next-gen' architectures you’re seeing—such as trispecifics or those targeting solid tumors—and how do they change our approach to treatment?

Mahmoudjafari: What's most exciting is how much more intentional these constructs are becoming. We're moving beyond CD3 engagement alone and starting to see multidimensional immune targeting. Trispecifics, for example, incorporate co-stimulatory signals like CD28 that may help address T cell exhaustion over time—one of the limitations we're finding clinically. Dual-targeted approaches are also important, particularly in multiple myeloma, where we're already thinking about antigen escape and sequencing implications. In solid tumors, the engineering is focused on selectivity and safety, with things like masked bispecifics that activate in the tumor microenvironment. Clinically, this is less about redirecting T cells and more about modulating immune durability and specificity—which is exactly where these therapies need to evolve.

Pharmacy Times: For many community centers, the 'fear of the unknown' regarding toxicity management is a major barrier. As we build this network, what would you say are the 3 most critical operational 'must-haves' for a site looking to transition from traditional biologics to a bispecific program?

Mahmoudjafari: From a program-building perspective, there are three things that absolutely need to be addressed early, and you have to get them right from the start.

The first is protocolized toxicity management. Each agent has varying incidence and duration of CRS and ICANS, so having institution-defined, clear grading, standing orders, and alignment across all care settings is essential. Without standardization, you risk unnecessary variability.

The second is a disciplined step-up dosing infrastructure. These therapies are schedule-dependent and require significant coordination between interdisciplinary teams—pharmacy, nursing, and care providers—particularly around monitoring and transitions between inpatient and outpatient settings.

The third is education with a clear escalation pathway for staff but, just as importantly, for patients and their caregivers because early symptom recognition drives outcomes. In my experience, the centers that succeed treat this less like a drug rollout and more like building a care delivery model around the therapy.

Pharmacy Times: We are seeing bispecifics move earlier into the lines of therapy. How should clinicians be thinking about 'sequencing' these drugs with existing standards of care, and what unique long-term safety signals (like late-onset infections) should we be watching for?

Mahmoudjafari: Sequencing has been the buzzword for quite some time, but it's becoming less about where a drug falls in the order of treatment and more about how it fits into the patient's overall immune trajectory. We're beginning to appreciate that prior therapies, T cell fitness, and target exposure all influence response to bispecifics. In multiple myeloma specifically, we're mindful of target selection and preservation—especially with BCMA-directed therapies—and how that impacts future options like CAR-T.

From a safety standpoint, what I see in practice is a shift from acute toxicity management, now that we have more experience, to longitudinal immune management. With hypogammaglobulinemia and recurrent infections, IVIG is becoming more routine to consider, especially for patients on continuous therapy. Clinically, we need to think beyond the initial response and manage these patients more like chronically immunosuppressed populations over time.

Pharmacy Times: One of the goals of this network is to foster real-time peer exchange. Looking at the next 2 to 3 years, what is the one 'unanswered question' about bispecifics that you hope this forum will help the medical community solve together?

Mahmoudjafari: For me, the biggest unanswered question is around treatment duration and optimization. We're largely continuing therapy until disease progression, but that may not reflect the underlying biology or what's best for patients long term. We're seeing very deep responses, and the question becomes: can we de-escalate, pause, or stop therapy safely — and if so, how do we identify those patients? In myeloma, minimal residual disease is one piece that's becoming more commonplace, but we don't have the full answer yet.

This also ties into infection risk, immune reconstitution, and the underlying elephant in the room: overall cost. It's both a clinical and a systems-level question. This is exactly where a network like this adds value—we need shared real-world experiences to find what's not just effective but optimal and to define what success looks like for these therapies long term.