Increasing Access, Using Technology, and Navigating Novel Therapeutics

Cancer care is continually evolving, with novel therapies offering unprecedented outcomes for patients across a range of cancer types. However, getting patients access to the latest innovations, such as chimeric antigen receptor (CAR) T-cell therapies in hematological conditions and precision medicine for solid tumors, can be difficult due to factors such as health system capabilities and high therapy costs.

Despite treatment guidelines often recommending novel therapies in earlier treatment lines, real-world practice is frequently very different. During a recent Institute for Value-Based Medicine event held in Richmond, Virginia, expert panelists discussed how their institutions work to make the most cutting-edge treatments available to as many patients as possible.

Optimizing Care for Myeloma and Breast Cancer
With the emergence of B-cell maturation antigen (BCMA)–directed CAR T-cell therapy and bispecific antibodies, treatment sequencing has been a frequent topic of discussion in multiple myeloma.

Moderator Victor Yazbeck, MD, an associate professor of internal medicine at Virginia Commonwealth University (VCU) School of Medicine and a hematologist-oncologist at VCU Health, opened the session by asking how clinicians should navigate sequencing. Guidelines from groups such as the International Myeloma Working Group recommend use of CAR T in the second line,¹ but bispecific antibodies may be easier to start with in real-world practice, he noted.

Hashim Mann, MD, a hematologist at VCU Medical Center, said it is easier to navigate when patients are ineligible for CAR T-cell therapy or do not want to receive it due to the risk of adverse events. But it is challenging when patients are eligible for both CAR T and bispecifics, he said. The preference at his institution is to try to implement CAR T-cell therapy prior to bispecifics when possible, which is consistent with current guidelines. This approach leverages the superior responses seen with CAR T when it is used prior to bispecific antibodies. When patients receive bispecifics first, there is typically a significant decrease in the efficacy of CAR T-cell therapy, and there may be issues manufacturing the CAR T-cell treatment to begin with, he noted.
“The point to be made now is CAR T is second line, and early referral on relapse is important, as well,” said Kevin Brigle, PhD, ANP, a nurse practitioner at VCU Medical Center. “[However,] we’re still seeing some of the same things happen where we run through all of the second-line, third-line, and fourth-line drugs before they bring [patients] in for CAR T.”

Brigle also reiterated that, as Mann noted, response rates and durations of response with CAR T-cell therapy are significantly improved when patients are treated in the second line compared with later lines. This is especially true when a bispecific has the same target as CAR T, and the only approved CAR T-cell therapies for myeloma target BCMA, which 3 of the approved bispecifics also target, Brigle explained.

There are also significant differences between CAR T and bispecifics in terms of toxicity expectations and monitoring requirements, said Kyle Zacholski, PharmD, BCOP, a clinical pharmacy specialist and program director, PGY2 Oncology Residency, at VCU Medical Center. With both, institutions are more often considering moving aspects of treatment to the outpatient setting, he explained. However, this is not without challenges, considering the toxicity profiles of CAR T-cell therapies and bispecifics, which both come with risks of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome.^2,3

“It is a big infrastructure change to prepare for managing bispecific therapies at an institution, because there needs to be timely access to cytokine release syndrome treatment and monitoring, which, from an inpatient side, was a big feat to accomplish, because we expected a large number of patients to start bispecific therapy for myeloma, for example,” Zacholski said. Getting all inpatient team members involved in the operationalization of bispecifics in the outpatient setting is key, he added, but different institutions must tailor strategies to their resources. Knowing the rates and timelines of toxicities is
also key, he said.

In breast cancer, personalized therapies have changed the treatment space in recent years and so has the integration of genomics into disease management. Moderator Kandace McGuire, MD, chief of breast surgery and interim senior vice president for the breast cancer service line at VCU Massey Comprehensive Cancer Center, kicked off the second session with a discussion of how clinicians should approach circulating tumor DNA (ctDNA) in real-world practice.

Lakshminarayanan Nandagopal, MD, a medical oncologist at Hematology Oncology Associates of Fredericksburg (HOAF) in Virginia, said ctDNA has different uses in different situations, but broadly speaking, ctDNA assays are useful to assess how a treatment is working in the advanced setting. ctDNA changes can precede progression on scans by as much as 3 or 4 months, he explained, which gives providers time to plan and think about what the next treatment option could be upon disease progression.

The decision to utilize ctDNA monitoring also should depend on the patient, according to Majd Issa, MD, a hematologist-oncologist at HOAF. For patients who are especially anxious and follow every test and laboratory results, it is important to explain that although ctDNA is a tool, it fluctuates and is unlikely to change the treatment plan.

William J. Irvin, Jr, MD, a medical oncologist and director of oncology at Bon Secours in Midlothian, Virginia, said he does not frequently use ctDNA testing to monitor for minimal residual disease because data on its potential benefits in breast cancer are largely immature. However, biomarker testing in metastatic disease can be useful upon disease progression to catch changes in metastatic disease prior to doing another biopsy, he said.

Antibody-drug conjugates (ADCs) are another innovation in breast cancer with the potential to improve outcomes. Matthew Whitehurst, MD, an oncologist-hematologist at HOAF, said that ADCs eventually will replace chemotherapy, despite being significantly more costly.

“They are costly,” Whitehurst said. “But study after study has shown that when compared with investigator’s choice, they are superior. And there are some unique [adverse] effects from these drugs, but in general, [they are] better tolerated by the patient. It’s very tough to cost save when you have a superior treatment that is less toxic.” Although getting approval can be difficult with these drugs, he said they will slowly move to earlier lines of therapy and replace chemotherapy, but not endocrine therapy for patients who benefit from that approach.

Mann added that he has had patients decline treatment based on the adverse effect profiles of ADCs, and picking patients who are right for this type of treatment is key.

The panel also touched on the issue of care access, with Irving highlighting the need to figure out how the costs of care can be managed without causing financial toxicity for patients. McGuire shared that a multidisciplinary clinic at VCU Massey Comprehensive Cancer Center has helped reduce financial toxicity for patients.

“It’s a drop in the bucket, ultimately, but being able to see your medical, radiation, and surgical oncologist all in the same visit does reduce travel time, reduces time off work, and allows you to bring that whole team of people to one meeting and meet all of your doctors,” McGuire said. Although it is easier to do this in the academic setting where staff are all at the same location, it is a model that can help patients get treated faster. Patients still pay multiple co-pays, but the model minimizes other potential barriers.

Improving Access to Oncology Care

Guang-Yu Yang, MD, PhD, a professor and chair of the Department of Pathology at VCU, led a discussion focused on precision medicine in genitourinary (GU) and gastrointestinal (GI) cancers, other areas where molecular testing has shifted the treatment paradigm. Panelists Asit Paul, MD, PhD, codirector of the Urologic Oncology Disease Working Group and a hematologist-oncologist at VCU Massey Comprehensive Cancer Center; and Matthew Reilley, MD, a GI medical oncologist and associate professor of medicine at the University of Virginia (UVA) School of Medicine in Charlottesville, and director of the phase 1 clinical trial program at UVA Comprehensive Cancer Center, highlighted the evolution of molecular diagnostics in cancer treatment.

“The change we like to see—to improve the survival in this disease, particularly advanced disease—we started seeing it because of the introduction of this molecular testing in the clinics and availability of the new drugs,” Paul said of the prostate cancer space. A notable example is germline or somatic testing, which allows clinicians to use targeted treatments such as PARP inhibitors in patients who could benefit from them. One pathway with a treatment gap is the PTEN mutation, which is targetable in other cancer types, Paul added. Overall, the field is moving toward targeted treatment based on molecular subtypes vs conventional histology and morphology-based treatment. Nowadays, early testing has become an important factor in treatment, as well, according to Reilley.

“In the metastatic setting for most GI malignancies, there are targets, and increasingly we know we need to know those targets up front,” Reilley said. “We need to have this testing done in the frontline setting and get an answer as quickly as possible so we can give patients the best possible treatment and not compromise overall survival.” This information also allows for comprehensive discussions with patients and fosters shared decision-making, he said.

Yang spoke about the importance of molecular testing, which is useful for grading tumors and identifying unknown-origin tumors, especially when a patient has multiple tumors and later-stage disease. This information can guide chemotherapy, radiation, and targeted therapies. Although primary tumor molecular testing is the baseline, ctDNA can then help determine whether residual disease exists. However, turnaround times for testing and costs can be barriers, depending on the size of the molecular profile being tested.

Using Technology to Increase Care Access in Rural Settings
Aside from therapeutic advances, technological innovations have potential to improve access for patients in rural areas, as discussed in the final panel. Renato Martins, MD, MPH, an oncologist at VCU Medical Center and professor of medicine and chief of the VCU Division of Hematology, Oncology, and Palliative Care, moderated the session with panelists Paul Kunk, MD, an associate professor and medical oncologist at UVA Health; Emily Kinsey, MD, a GI medical oncologist at VCU; and Reilley.

Martins explained that the gap in outcomes between rural and urban areas has only widened in recent years, with rural patients experiencing worse outcomes than those in urban locales. Fostering relationships with centers outside of large academic institutions is one way to provide patients in nonurban areas with opportunities for cutting-edge treatment, Kunk said.For patients who live far from the center where they receive treatment, Reilley emphasized that dropping everything for an in-person evaluation can cause a patient to lose half a day of work.

“That’s a big deal for a lot of people, and especially if they do well and live for a long time, that becomes an even bigger deal because of the financial toxicity of all these things,” Reilley said. “I do think telemedicine has helped, and I do hope that telemedicine sticks around, because I think it’s a way to be able to see and interact with patients more frequently without disrupting their lives as much.” Building better electronic medical record systems with better interfaces would also be helpful, he added.

Although certain assessments, such as a patient’s performance status, can be difficult to perform virtually, there are workarounds, such as a nurse physically performing an assessment and calling the doctor with updates, Kinsey said.
“It’s definitely not a perfect system, but it’s better than them having to drive every single time,” Kinsey said. “Though the one part that I think can be difficult is…the human aspect of it and having the difficult conversations.” Giving patients the option to have discussions virtually or in person is one way to navigate this issue, Kunk said.

One perk of virtual visits is that family members can be there with the patient, Kinsey noted. This may mean a number of people are on the call, but it is helpful for patients to have their support system present, she said. A barrier to virtual care is that licensing requirements may make care difficult across state lines, Kinsey explained. The ability to provide virtual care across states could also help with clinical trial enrollment, she noted.

“I think that we also need to invest in better technology to make it more palatable for everyone involved,” Martins said. This may entail upgraded rooms for virtual visits with better screen setups, which would be relatively inexpensive and could make virtual conversations feel more natural, for example.

As technology, including artificial intelligence, advances, the panelists agreed that there is potential for incorporating innovations to improve workflows and care quality.

References
1. Lin Y, Qiu L, Usmani S, et al; International Myeloma Working Group. Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee. Lancet Oncol. 2024;25(8):e374-e387. doi:10.1016/S1470-2045(24)00094-9
2. Wesson W, Dima D, Suleman N, et al. Timing of toxicities and non-relapse mortality following CAR T therapy in myeloma. Transplant Cell Ther. 2024;30(9):876-884. doi:10.1016/j.jtct.2024.06.012
3. Devasia AJ, Chari A, Lancman G. Bispecific antibodies in the treatment of multiple myeloma. Blood Cancer J. 2024;14(1):158. doi:10.1038/s41408-024-01139-y