CAR T-Cell Therapy, Biomarkers, Clinical Trials, and Bladder Cancer Advances

The pace of innovation in oncology has created both extraordinary opportunity and significant complexity for clinicians practicing across the full spectrum of care settings. From novel immunotherapy combinations in myeloma and bladder cancer to the challenge of ensuring that patients in community settings can access biomarker testing and clinical trials, the gap between what is possible and what is routinely delivered remains a defining issue.

The American Journal of Managed Care^® brought together academic and community oncologists, pharmacists, and urologists in Cincinnati, Ohio, on April 14, 2026, for the Institute for Value-Based Medicine^® event “Pioneering the Next Era of Oncology Care,” to examine how evidence, innovation, and collaboration can be translated into better patient outcomes.

Scaling Innovation: Delivering Targeted Therapies in Multiple Myeloma

In the opening panel, experts weighed chimeric antigen receptor (CAR) T-cell therapy vs bispecifics in myeloma, debating therapy sequencing, minimal residual disease (MRD)–guided decisions, infection management, and the emerging concept of functional cure. Edward A. Faber Jr, DO, MS, director of the adult bone marrow transplant and cellular therapy program and associate clinical professor of hematology/oncology at the University of Cincinnati (UC), served as the panel moderator and asked the panelists how they approach treatment decisions in an era of over 20 drug options, multiple combination treatments, and transplants as options.

Mark A. Marinella, MD, FACP, assistant clinical professor of medicine and oncologist/hematologist at Wright State University School of Medicine and Dayton Physicians Network, described his community-based approach by explaining that he initiates standard quadruplet induction in transplant-eligible patients and refers to academic partners for transplant evaluation. However, he acknowledged that the practice landscape is shifting. “It’s the most complicated cancer to treat,” he said, “because the data just change every week.”

Pierluigi Porcu, MD, professor of medicine and division chief of hematology and cellular therapy at the University of Kentucky College of Medicine, framed the central tension as a question of MRD. With modern frontline quadruplet regimens producing deeper responses than 3-drug regimens, MRD-guided decision-making is increasingly informing whether and when transplant is warranted. Nonetheless, he stated that autotransplants remain the standard of care, but acknowledged that this is changing. “I like to be cautious about completely changing certain patterns of care,” Porcu noted. In the community setting, MRD testing remains a source of uncertainty, with Marinella noting that outside of clinical trials, routine MRD testing in the community has lagged.

Jason Ernstberger, PharmD, BCOP, clinical hematology, oncology, cellular therapy pharmacist and director of the PGY-2 oncology residency program at University of California Medical Center, states that patient preference plays a meaningful role in deciding long-term treatment and said that “asking the patient is really important, because some patients might just have a lot of anxiety going off therapy—it’s like their crutch.”

The panel then turned to the operational realities of administering bispecific antibodies. Ernstberger outlined step-up dosing protocols for teclistamab, noting that an accelerated 48-hour interval between step-up doses was being used to shorten hospitalizations. He also described a strategy of liberal dexamethasone use in place of prophylactic tocilizumab to reduce the incidence and severity of cytokine release syndrome. Porcu reported that his institution was beginning to roll out outpatient step-up dosing for lymphoma bispecifics as a first step before extending the approach to myeloma bispecifics.

Beyond clinical protocols, structural barriers to bispecific access remain prevalent. Porcu noted that approximately one-third of patients in the University of Kentucky’s catchment area in Eastern Kentucky face inadequate caregiver support, which is important for safe outpatient bispecific administration. “Caregiver support adequate to deliver some of these complex therapies is a big problem,” he said. Marinella echoed this from the community perspective, noting that transportation and lack of family caregivers present greater practical barriers than insurance coverage in many cases.

The panel concluded by touching on the concept of “functional cure” in myeloma. Porcu defined it not as a biological elimination of tumor cells but rather as a state in which durable MRD-negative remission allows for therapy discontinuation and disease equilibrium. “The functional part probably means that ‘I’m not 100% sure I’m cured,’ so it still requires surveillance,” he said, “but the cure part, in my judgment, really has to have a discontinuation of therapy.”

Precision in Practice: From Biomarkers to Bispecifics in Lung Cancer

James F. Maher, MD, a medical oncologist at TriHealth and the panel moderator, opened by noting that his program’s biomarker testing rate, which had been only 65%, had climbed to 97% following electronic health record (EHR) integration. This change, he explained, allowed the team to track turnaround time, treatment initiation delays, and testing gaps directly from within the clinical workflow.

Zhonglin Hao, MD, PhD, coleader of the thoracic oncology program at the University of Kentucky Markey Cancer Center (Markey), and Rajeev Kulkarni, MD, hematologist/medical oncologist at Dayton Physicians Network, agreed on the imperative of reflex, upfront testing at the time of diagnosis. “As soon as we have cancer, we need to know the biology,” Hao said. “In the clinic, I routinely tell my patients, ‘That’s our goal, to get tested, because we need to know the biology to dispense the best treatment for you.’” Kulkarni, representing the community perspective, emphasized precision and actionability over breadth.

The panelists also discussed Medicare’s 14-day rule, which bundles lab tests into hospital payments when ordered within 14 days of discharge, creating financial disincentives and ultimately leading hospitals to delay testing. The panelists note that this can generate significant financial liability when next-generation sequencing testing is ordered during a hospital admission. Hao described a “financial toll” of more than $80,000 incurred. His institution has developed workarounds, including coordinating test orders through outpatient procedures performed between hospitalizations and timing orders to occur after hospital discharge.

The session also addressed the rapid integration of tarlatamab, a bispecific T-cell engager, into outpatient treatment programs. Kulkarni reported that his group was among the first in Dayton to offer outpatient tarlatamab, and Hao described a similarly smooth outpatient experience, with plans to further reduce hospitalization requirements. Both panelists emphasized the value of established institutional protocols in Epic, trained nursing staff, and close collaboration with their colleagues in the intensive care and pulmonology departments in enabling safe outpatient administration.

Looking ahead, the panelists anticipated continued acceleration in the approval of targetable biomarkers across earlier lines of therapy and the neoadjuvant setting. “Speedy, prompt testing before we are able to initiate treatment is key,” Hao observed, noting that delays attributable to biomarker testing, although frustrating for patients, are ultimately less costly than the downstream consequences of empiric, unguided treatment.

Collaborations in Today’s Environment for Successful Clinical Trials

The third panel, moderated by Jennifer Vaughn, MD, associate professor and hematology specialist at The Ohio State University Wexner Medical Center, tackled what may be one of the most systemically challenging issues in oncology: how to make clinical trials accessible to the patients who need them most.

Brian Mulherin, MD, of Hematology Oncology of Indiana and medical director of the American Oncology Network, shared that adult patients with cancer enroll in clinical trials at rates below 10% nationally, a rate that is especially low compared with that of pediatric oncology, where trial participation is often the default. Trial eligibility criteria are often built around idealized patients and may exclude the people most likely to be seen in community practices. Liberalizing those criteria, he said, is an important step the oncology community needs to ensure “you can actually recruit the patients that you are likely to see in a real-world setting.”

Rachael Morgan, PharmD, BCOP, clinical pharmacist and hematology/oncology pharmacy research and formulary manager at Markey, emphasized structural solutions such as decentralized trial designs that incorporate telehealth visits, remote monitoring devices, home phlebotomy, and mail-order drug delivery. These options, she said, can substantially reduce the burden of trial participation for patients who face transportation, childcare, or employment barriers. “By sequestering clinical trials in academic medical centers,” she noted, “we definitely limit not only our ability to enroll patients into those trials, but also [to] offer those treatments for those patients. Ultimately, I think the adjustment of trial designs and the development of decentralized clinical trials is a good strategy for this.”

The panelists also touched on the erosion of public trust in clinical research following the COVID-19 pandemic, which has since been amplified through social media and artificial intelligence–generated health content. Mulherin stated that physicians can no longer rely solely on the clinical encounter to counteract that distrust and need to be out in the community and online doing advocacy work. “There needs to be somebody on TikTok saying, ‘What is a clinical trial?’ and ‘What is a placebo arm?’ That’s what we need,” he said.

Vaughn also asked the panelists about the persistent tension between academic and community oncology practices in patient referral and trial access. Mulherin believes this is changing as physicians are starting to communicate better and more consistently with one another to give updates on patients. Morgan suggested making tumor boards accessible to community oncologists for real-time consultation, sharing trial-related order sets and educational materials across affiliate networks, and ensuring robust communication when patients are referred to an academic center for trial enrollment and then return home. She also proposed a compelling model that has been used outside of oncology but that she thinks could be applicable here as well, whereby the academic medical oncologist and the community oncologist have a paired telehealth appointment with the patient, combining the community physician’s longitudinal knowledge of the patient with the academic center’s trial expertise.

Advancing Customized Care in the Treatment of Bladder Cancer

“The initial transurethral resection,” Alberto Martini, MD, assistant clinical professor and director of research in the Department of Urology at the University of Cincinnati (UC) College of Medicine, says, “is generally the first procedure that we perform to diagnose and also to treat bladder cancer. It’s very important to do it thoroughly.” He reviewed some components of a high-quality transurethral resection of bladder tumor, including blue light cystoscopy to detect carcinoma in situ and occult flat lesions, procedural checklists, and early postoperative intravesical chemotherapy. He notes that these steps are evidence-based and cost-effective but inconsistently implemented.

The discussion then moved to risk stratification and the increasingly crowded landscape of agents for BCG-unresponsive non–muscle invasive bladder cancer. BCG has been the standard-of-care drug that has been around for over 4 decades; however, it does fail patients sometimes. Kamal Pohar, MD, chair of the Department of Urology at UC, who moderated the panel, shifted the conversation to discuss some of the current FDA-approved options in this space, including pembrolizumab and the combination of intravesical gemcitabine and docetaxel, which has generated compelling real-world evidence, although it is not yet the subject of a randomized trial.

Zin Myint, MD, medical oncologist at Markey, noted that although pembrolizumab produces a complete response in approximately 41% of patients, the systemic toxicity profile—with grade 3 or higher adverse events in approximately 20% of patients—must be weighed carefully in a population for whom radical cystectomy remains a potentially curative option. “Quality of life and what options are left, and whether patients want to preserve bladder [function]—these are the most important things,” Myint said.

Pohar introduced recently published data from a Patient-Centered Outcomes Research Institute–supported randomized trial comparing radical cystectomy with continued intravesical therapy in patients who preferred bladder preservation. Patients who underwent cystectomy reported superior outcomes across multiple quality-of-life domains. Martini explained that he “integrated this by not offering too many lines of therapy before pushing for a cystectomy.” He noted that repeated cystoscopies, procedures, and the psychological burden of recurrent cancer carry their own significant quality-of-life costs.

Myint reviewed the transformative impact of the EV-303 trial (NCT03924895) of neoadjuvant enfortumab vedotin plus pembrolizumab (EV-pembro) in the cisplatin-eligible population. Subsequent data from EV-304 (NCT04700124) have extended this finding to cisplatin-ineligible patients with similar efficacy. She noted that she had already begun using EV-pembro as neoadjuvant therapy in cisplatin-eligible patients, often securing insurance authorization despite the regimen’s pending formal approval status for that indication.

The session concluded with a discussion of circulating tumor DNA’s (ctDNA) growing role in bladder cancer. Myint described the prognostic signal from the NIAGARA study (NCT03732677), in which baseline ctDNA positivity correlated with poorer outcomes, while conversion to ctDNA negativity was associated with improved prognosis. Pohar noted, “There is a lot of enthusiasm in the field about the benefit of ctDNA. It’s under in-depth study in various areas, but is starting to be utilized quite a bit in clinical practice as a tool to make treatment decisions.”