Access and Innovation in North Carolina’s Research Triangle

From treating chronic lymphocytic leukemia (CLL) to using chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma, there was plenty of discussion on novel therapies July 30, 2026, as the Institute for Value-Based Medicine^® series traveled to the Raleigh-Durham area of North Carolina. Featured faculty came from the University of North Carolina School of Medicine and the UNC Lineberger Comprehensive Cancer Center, Wake Forest University School of Medicine, Atrium Health, and affiliates of Duke University Medical Center. The evening concluded with a discussion of how to bring the best therapies to patients most in need.

In CLL, Deciding Between Continuous vs Fixed-Duration BTK Regimens

Moderator Matthew Stuart McKinney, MD, of Duke Cancer Institute, opened the session “CLL: Navigating Treatment Options With BTK Inhibitors” by noting the field has moved well past first-generation covalent Bruton tyrosine kinase (BTK) inhibitors into “multiple generations of these medicines.” Alexandra Stefanovic, MD, of Duke Blood Cancer Center, said disease biology still drives her frontline choice.

For “patients who have high-risk CLL, particularly with a TP53 mutation, I would prefer a [covalent] BTK inhibitor in the first line and continuous treatment over time-limited treatment,” Stefanovic said, reserving the noncovalent pirtobrutinib (Jaypirca; Eli Lilly) for later lines, despite its expanding approvals.¹ Rebecca Garcia Hunt, PharmD, BCOP, CPP, of Atrium Health Wake Forest Baptist Medical Center, said her institution mirrors that approach but has moved quickly toward time-limited acalabrutinib (Calquence; AstraZeneca) and venetoclax (Venclexta; Genentech/AbbVie) regimens outside the TP53 population, describing treatment selection as a question of “pull-back cars.”

“What’s going to get you the most mileage?” Garcia Hunt asked. “Is it pulling back one agent really far or using things sequentially and thus reserving what you can for later lines of therapy?”

McKinney, citing data on the fixed-duration use of acalabrutinib and venetoclax in the phase 3 AMPLIFY trial (NCT03836261),² asked Stefanovic and Garcia Hunt what patient factors might influence the use of this regimen vs sequential continuous BTK inhibitor therapy.

Both emphasized that, in the absence of a TP53 mutation, the choice increasingly comes down to patient preference and logistics. Stefanovic cited the burden of venetoclax ramp-up visits vs the convenience of a BTK inhibitor that a patient can “take home.” Garcia Hunt noted that some patients want a “definitive course” they can complete, whereas others prefer the sense of control that comes with ongoing therapy.

As for adverse effects, Garcia Hunt described counseling patients on hypertension, diarrhea, and bleeding risk; she described a pilot program of early pharmacist phone visits to catch pirtobrutinib-related diarrhea sooner. Stefanovic said most toxicities emerge within the first 3 months; she sees patients monthly. Panelists discussed managing drug-drug interactions, particularly with azole antifungals, as well as the value of dose modulation that is now possible with newer formulations.

The panel closed by discussing community comanagement, with McKinney and Stefanovic describing direct phone access for referring oncologists, and looking ahead to the emerging class of BTK degraders, which work by using the cell’s natural recycling system to completely remove the entire BTK protein, helping to overcome the challenge of drug resistance.³

Although BTK degraders are experimental, Stefanovic said the class appears promising. “They have been used in clinical trials after the covalent and noncovalent BTK inhibitors and shown high response rates,” she said.

“Their big advantage is the absence of any cardiac [adverse] effects,” Stefanovic added. “While we don't have yet data or any approval in sight…I think they will find their place in the armamentarium.”

“Explosion” of Targeted Therapies in Breast Cancer, as Access Gaps Persist

Moderator Katherine E. Reeder-Hayes, MD, MBA, MSCR, of UNC Medicine, led the panel “Targeted Success: Operationalizing Therapies in Breast Cancer,” featuring Kelly Westbrook, MD, of Duke Health; Stephanie B. Wheeler, PhD, MPH, of UNC Gillings School of Global Public Health; Kerri Row, PharmD, BCOP, of Atrium Health Wake Forest Baptist Medical Center; and Aimee Faso, PharmD, BCOP, CPP, of UNC School of Medicine and North Carolina Basnight Cancer Hospital.

Westbrook described how an “explosion” of targeted options—including CDK4/6 inhibitors, PI3K/AKT pathway drugs, antibody-drug conjugates (ADCs), and immunotherapy—has shifted first-line decisions from biomarker-driven protocols toward individualized, molecularly guided choices. She cited the phase 3 INAVO120 trial (NCT04191499), in which adding inavolisib (Itovebi; Genentech) to palbociclib and fulvestrant led to a significant overall survival benefit in patients with PIK3CA-mutated advanced breast cancer.⁴ Westbrook also cited the approvals of trastuzumab deruxtecan (Enhertu; AstraZeneca/Daiichi Sankyo) for multiple regimens. Faso and Row said pharmacists are now pulled in earlier to manage more serious toxicities; Row noted that patients “often expect an easy pill to take” and are surprised by adverse effects such as hyperglycemia from PI3K inhibitors or pulmonary toxicity from newer ADCs. Proactive check-in calls, she said, have “made a really big difference” in keeping patients on treatment.

“We’ve been keeping a closer eye on some of our patients, especially if we know that they’re not as willing to tell us about some [adverse] effects,” Row said.

On genomic testing, Wheeler pointed to persistent access gaps. “We see lower availability and accessibility of these clinical innovations within populations that are most traditionally underserved,” she said, citing uninsured, rural, and minority populations. Tests such as Oncotype DX remain underutilized where they could help most, she said.

Westbrook and Reeder-Hayes discussed a growing shift toward liquid biopsy to detect ESR1 mutations at progression, citing faster turnaround times and reduced burden on patients living with metastatic disease for years. But on September 4, 2026, just 5 weeks after this panel, the FDA granted accelerated approval to the SERENA-6 trial (NCT04964934) regimen,⁵ which calls for using an FDA-approved test to shift patients with estrogen receptor–positive, HER2-negative metastatic breast cancer who are taking an aromatase inhibitor to camizestrant (Etcamah; AstraZeneca), along with a CDK4/6 inhibitor, when ESR1 mutations emerge.⁶

Row and Faso described tools for reaching rural patients, including community lab draws via Epic’s Care Everywhere, MyChart messaging, and electronic symptom-monitoring surveys that flag patients who need a callback. Reeder-Hayes credited telehealth as a COVID-19 pandemic–era gain that now supports shared care models with community oncologists.

Wheeler closed with data on adherence barriers—adverse effects, regimen complexity and cost, and behavioral beliefs—citing a scoping review that found only 14 of 56 adherence-intervention studies were randomized trials, and just 8 incorporated a technology component.⁷ Panelists ended on notes of cautious optimism about oral endocrine therapies such as the investigational oral selective estrogen receptor degrader giredestrant, which has an FDA action date of November 30, 2026.⁸ But Westbrook sounded a note of caution. “How are people going to afford this?” she asked.

Toward a “Functional Definition of Cure” With Bispecifics and CAR T-Cell Therapy

Moderator Sascha A. Tuchman, MD, MHS, director of the Multiple Myeloma and Amyloidosis Program at UNC Medicine and Lineberger, opened the panel “Scaling Innovation: Delivering Targeted Therapies, CAR-T, and Bispecifics in Multiple Myeloma” by asking fellow panelists how they sequence CAR T-cell therapy vs bispecific antibodies in patients relapsing after first-line treatment.

Haley Simpson, MD, PhD, of UNC Medicine, said she is “very convinced by the data that [have] come out recently that patients should get a [B-cell maturation antigen] T cell–redirecting therapy in the second line,” but that choosing between modalities comes down to a conversation about upfront monitoring burden, the indefinite duration of bispecific therapy vs a “one-and-done” CAR T-cell infusion, and each option’s adverse effect profile.

Samuel Rubinstein, MD, MS, of UNC Medicine, cited efficacy data supporting both approaches, with the phase 3 CARTITUDE-1 trial (NCT03548207) showing a 5-year progression-free survival (PFS) of 35%⁹ with ciltacabtagene autoleucel, and the phase 3 MajesTEC-3 trial (NCT05083169) showing 3-year PFS of 83% with teclistamab and subcutaneous daratumumab.¹⁰ He noted that manufacturing a CAR T-cell product fails approximately 40% of the time in patients previously exposed to a bispecific compared with less than 10% in bispecific-naive patients.

“If I’m deciding to give a patient a bispecific, I’m essentially taking CAR T off the table,” he said.

John McKay, DO, of Wake Forest University School of Medicine, agreed the decision is largely individualized, calling on clinicians to weigh the intensity of CAR T-cell therapy against bispecifics’ long-term infection risk. He flagged concerns about delayed neurotoxicities, including parkinsonian-type features seen in a small subset of CAR T-cell recipients.

Regarding adverse effects, Simpson said better disease control before CAR T-cell infusion appears to reduce parkinsonism risk, which is currently estimated at 2% to 3%.¹¹ Rubinstein added that approximately 1 in 10 CAR T-cell recipients will experience durable morbidity or mortality tied to the product itself. “There’s really no free lunch,” he said.

The panel also discussed the distinct toxicity profile of the bispecific talquetamab (Talvey; Johnson & Johnson), including dysgeusia, weight loss, and emerging ataxia. “That’s an agent that I don’t think most of us like to use until we really need to, because it’s a difficult drug to tolerate, but it can be very effective,” especially for high-risk patients bridging to CAR T-cell therapy, Rubinstein said.

Simpson said toxicities affect 70% to 80% of patients on this bispecific, which targets CD3 on T cells and GPRC5D on myeloma cells.¹²

Asked how community capacity should be built for these therapies, McKay pointed to sharing experiences and phone access with community oncologists; Rubinstein predicted that bispecifics may become the frontline standard of care and stressed that emergency and neurology colleagues need to be prepared to manage cytokine release syndrome and neurotoxicity.

Still, McKay said, today’s patients are achieving a “functional definition of cure,” and fellow panelists concurred. Rubinstein pointed to sustained deep remissions with daratumumab-based induction and transplant, while Simpson cited 5-year follow-up data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) showing 33% of patients were progression-free, calling it comparable to how oncology defines cure in solid tumors.¹³

Removing Payer Barriers, Working With “Trusted Messengers”

Atrium Health’s LeAnne Kennedy, PharmD, opened the final session, “Improving Cancer Care Access Across Urban, Suburban, and Rural North Carolina,” by noting that only about 20% of patients with cancer are treated at academic medical centers.¹⁴ Kennedy then asked Laura Alder, MD, of Duke Cancer Institute; Nadine Barrett, PhD, MA, MS, of Wake Forest University School of Medicine; and Kamakshi V. Rao, PharmD, BCOP, FASHP, FHOPA, of UNC Medical Center, what keeps complex care from reaching patients closer to home. Barrett noted that North Carolina has only 3 National Cancer Institute–designated cancer centers serving 100 largely rural counties, and pointed to mobile units as one way to extend both screening and treatment access while maintaining ties to academic centers. As a solution, Alder emphasized partnership with community physicians so patients can be transitioned back after a clinical trial or bispecific initiation.

Rao framed the barriers in 3 categories: patient-level factors, institutional infrastructure built around urban hubs, and payer policy. “I may have 200 infusion chairs in the Triangle area, but I have 12 outside of there,” she said, even though a large percentage of patients are coming from beyond North Carolina’s Research Triangle, bounded roughly by Raleigh, Durham, and Chapel Hill.

Payer site-of-care restrictions are a recurring obstacle, Rao said, recounting a case where a payer authorized chemotherapy at a cancer center but not the accompanying pembrolizumab (Keytruda; Merck) infusion at the same site. Barrett raised parking fees as an avoidable, institution-created barrier. “We’re not waiting for government policy,” she said, “to tell us to make our garages free for people for treatment. That is an institutional policy and practice.”

The panel discussed extending complex therapies such as bispecific T-cell engagers into community settings by sharing protocols, building peer networks among providers, and using “systemness,” described as a centralized academic “brain trust” made accessible to suburban and rural partners, to build local confidence in managing toxicities.

Regarding clinical trial access, Barrett described community clinics as eager but underresourced, lacking the administrative infrastructure to run trials alongside routine patient loads, and cited research suggesting some clinics simply don’t see patients at the disease stage a given trial requires. She also shared a story from her time at Duke, where sustained community engagement led a church to host a Helicobacter pylori research study that drew 92 participants in 2 hours.

“Since then, we’re doing more and more of that—engaging our communities,” Barrett said. “We’re talking about the things that people are afraid of, and they did it, because…we were working with trusted messengers.”

References

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