UAB Works to Deliver Cutting-Edge Cancer Therapies, Reach Every Patient

The Institute for Value-Based Medicine^®, hosted by The American Journal of Managed Care^® (AJMC^®), held its October 1, 2026, meeting in Birmingham, Alabama, with 4 panels of University of Alabama at Birmingham (UAB) faculty, who discussed how new therapies are reshaping bladder cancer and multiple myeloma care—and what it takes to deliver them.

In Bladder Cancer, a New First-Line Standard and Interpretations on an Old Standby

Moderator Charles Peyton, MD, a urologic oncologist at UAB, noted that the FDA expanded the approval of the antibody-drug conjugate (ADC) enfortumab vedotin (Padcev; Astellas/Pfizer) plus pembrolizumab (Keytruda; Merck), the combination EVP, for perioperative treatment of muscle-invasive bladder cancer in July 2026.¹ Mollie DeShazo, MD, a genitourinary medical oncologist, said very few of her patients now receive platinum-based chemotherapy, citing complete response rates of 56% with EVP vs 33% with gemcitabine-cisplatin.² Exceptions include patients with poorly controlled diabetes, because enfortumab can raise blood glucose, and transplant recipients, who face about a 30% risk of rejection with immunotherapy. Mersadies Orr, CRNP, said EVP is generally better tolerated than cisplatin, but clinicians must watch for toxicities early and plan for the burden of treatment duration and visit frequency.

Peyton shared how he explains to patients the tolerability differences in chemotherapy vs immunotherapy. “I always tell them that [adverse effects] of chemotherapy, [that] everyone gets them and they’re annoying and everyone gets the nausea, the vomiting, the hair loss—and from time to time, leukopenias,” he said. “But when I talk to people about immunotherapy, I said the [adverse effects] are a little bit more tolerable, but when you get a bad one, they’re really worse.”

DeShazo agreed. “Immunotherapy is great until it’s not,” she said, estimating that approximately 10% of patients have a life-altering toxicity, which can include having to take thyroid medication forever.

Thomas Chi, MD, MBA, chair of urology at UAB, said it’s not that easy for Alabama residents to travel to Birmingham for care—especially compared with the resources some of his patients had when he practiced in San Francisco, California. The ability to travel can be a factor in decision-making.

“You don’t have to drive very far from here, where people don’t have the money to actually get to places where they need to go to get these immunotherapies,” he said. “Then, if you’re talking about 10% of people potentially getting a life-altering side effect, to me, I mean, it brings up the idea around costs…. I’ve pushed Charles to think about, ‘What’s the future look like where we no longer do surgery?’ If we’ve got amazing chemo and immunotherapies, we’ve got radiation therapy, that would totally transform the landscape of bladder cancer, but what does it actually do for our patients from an access to care standpoint?”

Chi asked whether immunotherapies can be made more accessible to patients, and DeShazo said that subcutaneous (sub-Q) formulations and community urology infusion suites are helping achieve this.

Peyton and DeShazo were critical of adding checkpoint inhibitors to intravesical BCG for BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC). Among a group of phase 3 trials, ALBAN (NCT03799835) was negative, whereas CREST (NCT04165317) and POTOMAC (NCT03528694) showed disease-free survival (DFS) gains of 3 to 5 percentage points at 2 years—benefits that appeared tied to maintenance therapy.³ “In my mind, these 3 trials proved 1 thing: BCG works great,” said Peyton, noting 2-year DFS of approximately 80% in control arms. He cited toxicity rates of 13% to 20% and 2 deaths in CREST.⁴

DeShazo said many patients labeled “BCG failures” simply did not receive adequate maintenance BCG and that a 3% to 4% improvement does not justify a 10% risk of life-altering toxicity. Peyton, who serves on the National Comprehensive Cancer Network guidelines panel, noted that the panel ranked durvalumab (Imfinzi; AstraZeneca) plus BCG, approved by the FDA in May based on POTOMAC,⁵ as “useful in certain circumstances,” the lowest category available.⁶ Chi said large private urology groups have financial incentives to bring infusions in-house, and direct-to-consumer advertising complicates the message; guidelines, he said, may be the strongest lever to change behavior.

Metastatic disease and biomarkers. In metastatic disease, EVP is now the first-line backbone, with a response rate of approximately 68% based on the EV-302 trial (NCT04223856)⁷ compared with 30% to 50% for second-line options, panelists said. Platinum chemotherapy has moved to later lines or is reserved for patients with early immunotherapy toxicity or variant histology, such as squamous features. Complete responses, once rare in metastatic disease, are now appearing in clinic.

Orr said she orders genomic testing that includes FGFR and HER2 when patients present with metastatic disease, so that results do not delay later treatment decisions. DeShazo said circulating tumor DNA may deliver the most value, because it could lead to escalation. “Do we need to keep doing another year of Keytruda because the trial said 2 years?”

Shared decision-making and cost. Peyton described the CISTO trial (NCT03933826),⁸ an observational study of approximately 570 patients with BCG-NMIBC. Patients who chose radical cystectomy reported equivalent or better emotional functioning and lower anxiety and depression than those who kept their bladders. “Keeping your bladder doesn’t always mean you feel better,” Orr said. Chi said surgeons may have a bias toward promoting surgery and that advocacy groups such as the Bladder Cancer Advocacy Network are underused.⁹

After decades with only valrubicin, there are now 4 FDA-approved options for BCG-unresponsive disease, but Peyton said one solution, the TAR-200 device (Inlexzo; Johnson & Johnson),¹⁰ can cost approximately $800,000 a year. “How do you price a human life?” Chi asked.

Myeloma: Quadruplets and Redefining High Risk

Moderator Susan Bal, MD, of the O’Neal Comprehensive Cancer Center at UAB, said that at the recent International Myeloma Society meeting in Glasgow, Scotland, a long-term Perseus trial (NCT03710603) update showed 6-year progression-free survival (PFS) exceeding 80% with a quadruplet, autologous transplant, and limited-duration, minimal residual disease (MRD)–guided maintenance.¹

Heidi Worth, MD, said she uses quadruplets for most patients, including transplant-ineligible patients, based on the IMROZ (NCT03319667)¹² and CEPHEUS (NCT03652064) trials,¹³ reserving triplets for frail or older patients. Laura Joiner, PharmD, BCOP, said a new on-body delivery system for isatuximab, which administers the drug in less than 20 minutes, will reduce time toxicity and chair time and could support home administration. The on-body injector, sold as Sarclisa Escena (Sanofi), received FDA approval in July.¹⁴

Gayathri Ravi, MD, presented UAB data on 319 patients treated with quadruplet induction and transplant; 66, approximately 1 in 6, progressed within 3 years.¹⁵ Patients who relapsed within 24 months had a median PFS of approximately 3 months on subsequent therapy vs 7 to 8 months for later relapses. Median overall survival (OS) was 8.1 months for relapse within 18 months and 23.8 months for relapse within 36 months. “We cannot ignore patients who are relapsing after 18 months,” Ravi said. Patients who received T-cell–redirecting therapy at relapse had response rates near 90% vs approximately 30% with standard therapy.

Scaling T-cell–redirecting therapy. MajesTEC-3, (NCT05083169),¹⁶ led by UAB’s Luciano Costa, MD, PhD, the Mary and Bill Battle Professor of Multiple Myeloma and director of the multiple myeloma research and treatment program, propelled the March 2026 approval of the bispecific T-cell engager (BiTE) teclistamab (Tecvayli; Janssen) plus targeted monoclonal antibody daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen) after 1 prior line.¹⁷ Worth called MajesTEC-3 among the most practice-changing trials of recent years, with 3-year PFS of approximately 83% vs 30% for standard care.¹⁶ Bal noted many patients in the trial were daratumumab-naive, making MajesTEC-3 more reflective of US practice.

Ravi reviewed CARTITUDE-4 (NCT04181827), in which ciltacabtagene autoleucel (cilta-cel/Carvykti; Legend/Janssen), a chimeric antigen receptor (CAR) T-cell therapy, achieved MRD negativity in close to 61% of patients vs 15% with standard care. According to the New England Journal of Medicine study, PFS at 12 months was 75.9% (95% CI, 69.4%-81.1%) in the cilta-cel group and 48.6% in the standard-of-care group.¹⁸

Joiner described UAB’s criteria for outpatient step-up dosing: being able to reach the center within 30 minutes, a 24/7 caregiver, and the ability to monitor temperature and vital signs. Prophylactic tocilizumab has cut cytokine release syndrome (CRS) rates from 60% to 70% to approximately 10%, mostly grade 1, she said.

“The data also support that prophylactic tocilizumab not only reduces the rate of CRS and creates that safety net, but it also reassures us in some of the data that’s recently come out that it does not impair the efficacy of our T-cell engager,” she said. “It’s certainly a win-win there. When you’re thinking about value-based medicine, now that it’s encouraged in the guidelines, there’s a place for that. If you’re worried about payers not reimbursing for a dose of prophylactic [tocilizumab], I think the benefit of accessing therapy outweighs any potential cost with a 1-time infusion.”

Worth said aggressive antimicrobial prophylaxis and routine immunoglobulin replacement have sharply reduced severe infections. “It’s not tec-dara, it’s tec-dara-I,” Bal said, referring to intravenous (IV) immunoglobulin. Ravi said delayed neurotoxicity affected approximately 17% of cilta-cel patients in CARTITUDE trials; Parkinsonism-like movement disorders, seen in approximately 5%, are often irreversible, making early recognition and treatment critical.

“The next frontier of what we want to achieve is how do we bring these innovations to every myeloma patient,” Bal said.

Precision in Practice: Launching New Agents to Fight Lung Cancer

The panel, titled “Precision in Practice: Delivering Targeted Therapies and Bispecifics in Lung Cancer,” turned into a working session on how UAB brings new targeted agents and bispecific antibodies from approval into practice. Aakash Desai, MD, MPH, a thoracic oncologist and phase 1 medical oncologist at UAB, had been billed as the moderator, but at the start, he switched roles with Mehmet Akce, MD, who leads the precision medicine phase 1 program at O’Neal Comprehensive Cancer Center. Akce put the questions to Desai and to Clayton Tynes, PharmD, pharmacy director for cancer services at UAB Medicine.

In EGFR-mutated NSCLC, a crowded front line. Desai said the EGFR-mutated non–small cell lung cancer (NSCLC) space has been “very active” over the past 3 to 5 years. Osimertinib (Tagrisso; AstraZeneca), an EGFR tyrosine kinase inhibitor (TKI) first given as a monotherapy, was the frontline standard for several years, but a pair of regimens has now largely replaced it. One is osimertinib plus chemotherapy, based on the FLAURA2 trial (NCT04035486).¹⁹ The other is amivantamab (Rybrevant; Janssen) plus lazertinib (Lazcluze; Janssen), based on the MARIPOSA trial (NCT04487080).²⁰ Amivantamab is a bispecific antibody that targets EGFR and MET.

Desai described the challenges that existed with the IV form of amivantamab and how things have improved with a new sub-Q formulation. “When we started, we used to split the dose as per the FDA label for day 1 and day 2,” he explained. “Patients had to come in 2 days to get the infusion,” with 40% to 50% of patients experiencing infusion-related reactions, as well as skin toxicities and sometimes blood clots.

“Over the last year or so, there has been tremendous effort on trying to make this drug available subcutaneously,” Desai said. “There have been studies which have shown that the efficacy is quite similar, but the tolerability has improved since going to the subcutaneous formulation. Of course, this reduced the infusion-related reactions a lot.”

In December 2025, the FDA approved a sub-Q formulation, amivantamab and hyaluronidase-lpuj (Rybrevant Faspro), for all indications of the IV drug; this was based on the PALOMA-3 trial (NCT05388669), in which 13% of patients given the sub-Q form had systemic administration reactions compared with infusion-related reactions in 66% of patients given the IV form.²¹

The sub-Q version keeps the efficacy “while reducing the toxicity and making it more tolerable and also logistically easier,” Desai said.

For Tynes, the advantage is operational. UAB has many patients who need dedicated nursing for complex IV therapies. The sub-Q product can be given in an injection chair, and patients no longer need to return on day 2. Because infusion reactions had held the drug back, it “should, in theory, provide some enhanced access—maybe even outside some academic centers,” he said.

Desai agreed. When IV amivantamab was first launched, he said, community practices were hesitant to start it. This meant UAB saw an influx of patients. The 2 first-line options have comparable efficacy, he said, so the choice has become largely a matter of provider preference. Desai starts with osimertinib plus chemotherapy because amivantamab is harder to tolerate than a third-generation TKI. He saves amivantamab plus chemotherapy, which is approved in the second line based on MARIPOSA-2 (NCT04988295), for progression.²² Datopotamab deruxtecan (Datroway; AstraZeneca/Daiichi Sankyo) received accelerated approval in 2025 for previously treated EGFR-mutated NSCLC.²³ Desai generally reserves it for the third line.

He stressed the importance of waiting 2 to 3 weeks to receive results from next-generation sequencing (NGS) before starting immunotherapy. Giving a checkpoint inhibitor first and then switching to osimertinib raises the risk of pneumonitis. Patients who are highly symptomatic can start chemotherapy alone while results are pending.

At progression, NGS with tissue is the gold standard, but UAB also uses liquid biopsy when tissue isn’t feasible. Desai said he pushes for a biopsy when a patient who had been responding suddenly declines. He said 5% to 8% of EGFR-mutated tumors transform into small cell lung cancer (SCLC), “and that definitely changes the way we manage these patients.”

With tarlatamab, clinicians learn from hematology. Tarlatamab-dlle (Imdelltra; Amgen) is a DLL3-directed BiTE approved for patients with SCLC who have progressed on or after platinum-based chemotherapy, based on DeLLphi-304 (NCT05740566).²⁴ Tynes said it was UAB’s first effort to bring a bispecific into use outside hematology, and it meant a new care team had to learn to manage CRS.

A pharmacy resident reviewed UAB’s early patients. CRS rates were similar to those in the trial, but immune effector cell–associated neurotoxicity syndrome (ICANS) was more common. Tynes attributed this partly to the BiTE being used to treat a higher share of patients with brain metastases than the trial enrolled. That created a new clinical problem: telling ICANS apart from symptomatic brain metastases.

UAB initially admitted patients for 24 hours after the first doses. They stayed with a team experienced with CAR T-cell therapy and bispecifics, with CRS and ICANS checks about every 4 hours. Desai said UAB also modeled care based on hematology’s outpatient bispecific programs and gave 3 or 4 fully outpatient infusions before the label changed. These were given to patients whose caregivers were confident in monitoring their temperature and blood pressure at home. He said UAB was among the first centers outside clinical trials to give tarlatamab as an outpatient therapy and cited a recent multi-institutional paper.²⁵

In September, the FDA cut monitoring after the first 2 doses from 22 to 24 hours to 6 to 8 hours. Patients now need a next-day assessment and must stay within 1 hour of an appropriate care setting for 48 hours with a caregiver.²⁶ Desai said the team planned a multidisciplinary meeting to revise its workflow.

Tynes urged caution because CRS typically begins beyond what is now the new monitoring window. Patients still need to understand the risks and have a caregiver. They also need to be able to reach a care site that can quickly give dexamethasone, fluids, and tocilizumab. “You still have to consider the support structure the patient has as well as your system,” he said.

Akce added that education must reach beyond the cancer center. He described a call from an outside emergency department that was working up a patient for sepsis a day or two after a tarlatamab dose. Staff there didn’t know the patient was on a novel therapy, and UAB had to advise high-dose steroids and a transfer. “When the patients go to peripheral hospitals, they need to at least let them know that they are on a novel therapy,” he said.

In SCLC, tarlatamab moves up as later-line options narrow. “It’s a very exciting time for small cell,” Desai said. In September, Amgen announced that the DeLLphi-305 trial (NCT06211036) met its primary end point of OS. The trial, in which UAB took part, compared tarlatamab plus durvalumab with durvalumab alone as first-line maintenance in extensive-stage SCLC.²⁷ If the combination is approved, tarlatamab would move from the second line to maintenance after carboplatin-etoposide-durvalumab. That would leave a greater need for second- and third-line therapies.

Those options are shrinking. In late September, Daiichi Sankyo and Merck withdrew their application for accelerated approval of ifinatamab deruxtecan (I-DXd), a B7-H3–directed ADC. The FDA had said phase 2 data showing a 48% response rate did not meet accelerated approval requirements.²⁸ Jazz Pharmaceuticals also plans to withdraw the single-agent second-line indication for lurbinectedin (Zepzelca) after the confirmatory LAGOON trial (NCT05153239) missed its OS end point. Lurbinectedin’s first-line maintenance indication with atezolizumab remains.²⁹

Two other B7-H3 ADCs beat topotecan in trials run entirely in China, Desai said. “The question now becomes, when will we get access to those, and how will they perform in a global population?” he said.

Akce asked whether DLL3-directed ADCs could work after tarlatamab. Desai pointed to breast cancer, where a second HER2 ADC can still work after trastuzumab deruxtecan (T-DXd; Enhertu; AstraZeneca/Daiichi Sankyo). Resistance to tarlatamab isn’t well understood, he said. Even if DLL3 expression drops, an ADC with a cleavable linker might keep some activity.

HER2-Mutant NSCLC. “These treatment options keep moving back and forth in terms of sequencing,” said Desai. Trastuzumab deruxtecan was first approved in the second line based on DESTINY-Lung01 (NCT03505710)³⁰; since then, 2 oral HER2 TKIs have received accelerated approval in the first line:

• Zongertinib (Hernexeos; Boehringer Ingelheim), in February 2026 (Desai led UAB’s study team for this trial)³¹
• Sevabertinib (Hyrnuo; Bayer), in September 2026, with a 75% response rate³²

At the 2026 World Conference on Lung Cancer, DESTINY-Lung04 (NCT05048797) compared first-line T-DXd with pembrolizumab plus platinum-pemetrexed. Median PFS was 14.3 months vs 8.3 months (HR, 0.63).³³ Desai still prefers a TKI first because of tolerability and response rates, noting that T-DXd brings nausea, gastrointestinal effects (GI), and myelosuppression. He would use T-DXd second and said chemoimmunotherapy still has a role.

Navigating Barriers to Care in a State Where One Payer Dominates

The final panel was moderated by Anna Lee Petitt, PharmD, an infusion pharmacist at UAB’s Kirklin Clinic. Panelists were Stephanie Adams, PharmD, also a UAB infusion pharmacist; Cameron Britton, MD, a urologic oncologist at UAB; and Tynes.

The panelists didn’t shy from the reality that has long shaped access in the state: According to the American Medical Association, Blue Cross and Blue Shield of Alabama holds 86% of the state’s commercial market.³⁴ “When a payer has 80% of the market, that can certainly impact patients’ access to therapies,” Tynes said.

That impact shows up in several ways:

• Preferred products: preferred agents, biosimilars, and oral pathways
• Adoption speed: how quickly a health system can offer something like a new sub-Q formulation, which improves the patient experience but not efficacy
• Travel: when a therapy isn’t preferred, patients may have to return to the infusion clinic

Adams said easier options, such as sub-Q and oral drugs, matter in a largely rural state where many patients have low health literacy. Her own family travels 2.5 hours for treatment.

Britton described the situation in BCG-unresponsive NMIBC. The new intravesical therapies there “typically run in the 6 figures for full treatment cycles,” he said. For the gemcitabine intravesical system, the TAR-200 device, insurers have mostly said they will pay 80%. “Patients are still saddled with 5-figure bills, and they just can’t afford it,” he said. “So, we have to think of other options.”

Financial toxicity and shared decision-making. Tynes said UAB serves a higher-than-average share of uninsured patients. A dedicated team works to provide the same level of care regardless of payer, which he acknowledged “may be in a fortunate position.”

Britton studied out-of-pocket costs for men with advanced prostate cancer during his fellowship. He said getting a real number for what a patient will pay is “basically impossible,” especially with commercial insurers, even though patients want to make treatment decisions that fit their financial goals. Medicare is usually more transparent, he said.

Adams has received oncology care at UAB. She said she recently learned of a co-pay assistance program that would have saved her $10,000 over 6 years. “Even knowing that and being in it, it’s still challenging navigating that,” she said.

Travel, telehealth, and outreach. Tynes said UAB’s cancer care is centered at the downtown Kirklin Clinic and the Acton Road Infusion Clinic. Patients appreciate Acton Road’s “smaller boutique feel,” and UAB is considering additional infusion sites to serve all patients, not just those with cancer. Adams said the lighter traffic and easier parking at satellite sites make a real difference. Britton uses telehealth for postoperative check-ins and some new consults. Patients “don’t have to drive into the city. They don’t have to take [paid time off],” he said.

On early-onset cancers, Petitt said the infusion staff is seeing GI cancers in much younger patients. Adams, a young survivor herself, said she became an infusion pharmacist to give patients hope. “I can say, I’ve sat in that chair, and this is really hard, but it’s doable.”

Linking patients who screen positive to an oncologist “just comes down to personal relationships” with primary care providers, Britton said. Putting oncologists in satellite campuses also helps. Tynes pointed to free prostate-specific antigen screenings that UAB volunteers provide at Auburn University’s annual AUTLIVE men’s basketball game, an effort championed by former head coach Bruce Pearl.³⁵ An audience member from O’Neal described outreach through faith-based groups that teaches rural and underserved communities, including patients of color, about clinical trials and how to access care.

Clinical trials. Matching patients to trials depends on which trials are open, and that, in turn, depends on which physicians bring them to UAB, Britton said. Urologic oncology trials are so niche that UAB may enroll only 2 or 3 patients over 2 years, but community sites could raise those numbers. Adams noted that making trials more accessible is an advocacy priority of the Hematology/Oncology Pharmacy Association. Tynes said collaboration is key. There’s opportunity, he said, “to collaborate across the state with other sites in making sure that they’re aware of the trials that we have open, what are the screening and eligibility criteria, so that we can collaborate together when we may have something for one of their patients.”

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