B-CELL LYMPHOMA

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase II ZUMA-12 trial

First-line treatment with the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) achieved a high complete response rate among patients with high-risk large B-cell lymphoma, according to findings from the ZUMA-12 trial (Nat Med 2022; doi:10.1038/s41591-022-01731-4). In this Phase II, multicenter, single-arm study, researchers evaluated axi-cel as a first-line treatment for 40 patients with high-risk large B-cell lymphoma. The primary outcome of the research was complete response rate. Secondary outcomes included objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse, and blood levels of CAR T cells and cytokines. The primary endpoint was met with a 78 percent complete response rate and 89 percent objective response. The estimated overall survival rate at 12 months was 91 percent, according to the study authors. As of May 2021, they reported that 73 percent of patients remained in objective response. Median DOR, EFS, and PFS were not reached. In terms of safety, Grade >=3 cytokine release syndrome and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. The researchers reported no treatment-related Grade 5 events. "Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days," the researchers stated. "We conclude that axi-cel is highly effective as part of first-line therapy for high-risk large B-cell lymphoma, with a manageable safety profile."

AUTHOR COMMENTARY: "Existing treatments for large B-cell lymphoma consist of 6 months of chemotherapy. These results provide evidence that axi-cel may offer effective responses in one treatment and eliminate the need for patients to be exposed to other therapies," noted Sattva Neelapu, MD, Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "A randomized trial is necessary to confirm these results. I am highly encouraged that with additional studies we can move CAR T-cell therapy to be the first treatment for high-risk lymphoma patients."

HEALTH CARE BARRIERS

Self-reported transportation barriers to health care among U.S. cancer survivors

A recent study found that transportation barriers-including access to public transportation or a personal vehicle-disproportionately impact cancer survivors. The data shows that this is especially true if they are young, uninsured, or live below the poverty line (JAMA Oncol 2022; doi:10.1001/jamaoncol.2022.0143). Given their increased health care needs, as well as an elevated risk of comorbidities and subsequent cancers, timely access to health care is crucial for cancer survivors. This cross-sectional study surveyed 148,195 participants 18 years and older. Of those, 11,586 had a cancer history. They were asked: "Have you delayed getting care in the past 12 months because you did not have transportation?" Transportation barriers between survivors and adults without cancer were compared, stratified by age group, and researchers assessed associations between sociodemographic factors, health, and health care-related factors. Data showed that cancer survivors were nearly twice as likely to report delays in care due to transportation barriers in the past 12 months compared with adults without a cancer history (3.1% vs. 1.8%), according to the study authors. Additionally, they reported that cancer survivors who were younger, poor, uninsured or publicly insured, unmarried, or had functional limitations or multiple comorbidities were more likely than other survey participants to experience a delay in necessary health care due to transportation barriers.

AUTHOR COMMENTARY: "More comprehensive approaches are needed to identify and overcome transportation barriers to care, with consideration of related barriers, including financial limitations and food or housing insecurity," noted Changchuan Jiang, MD, MPH, a Hematology-Oncology Fellow in Department of Medicine at Roswell Park Comprehensive Cancer Center. "This effort will require the involvement of many different groups, including physicians, nurses, social workers, and insurance companies. Overall, overcoming transportation barriers is an essential part of larger efforts to improve health care for patients with cancer, and it could be more cost-effective for health care facilities and insurance companies to simply provide reliable transportation services for these patients."

MAMMOGRAPHY

Cumulative probability of false-positive results after 10 years of screening with digital breast tomosynthesis vs. digital mammography

Half of all women will experience at least one false-positive mammogram over a decade of annual breast cancer screening with digital breast tomosynthesis (3D mammography), according to a recent study (JAMA Netw Open 2022;5(3):e222440). The findings also showed that the risk of false-positive results after 10 years of screening is considerably lower in women screened every other year. In this observational comparative effectiveness study, researchers analyzed data collected by the Breast Cancer Surveillance Consortium on 3 million screening mammograms for 903,495 women aged 40-79 years. Data revealed that the probability of receiving at least one false-positive recall over a 10-year period was slightly lower with 3D compared to 2D digital mammography. The decrease in false positives between these two modalities was greatest for women with non-dense breasts and those who had annual screenings, according to the study authors. The research team also estimated that, over 10 years of annual tomosynthesis screening, 50 percent of women will experience at least one false-positive recall, 17 percent a false-positive short-interval follow-up recommendation, and 11 percent a false-positive biopsy recommendation. Regardless of the type of screening, the study authors found that false-positive results were significantly lower for older age groups, as well as women with entirely fatty versus extremely dense breasts. "The findings of this study suggest that digital breast tomosynthesis is associated with a lower cumulative probability of false-positive results compared with digital mammography; biennial versus annual screening was associated with larger reductions in cumulative false-positive risk for both modalities," according to the study authors, who concluded, "Our study offers new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians; however, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis."

AUTHOR COMMENTARY: "Despite the important benefit of screening mammography in reducing breast cancer mortality, it can lead to extra imaging and biopsy procedures, financial and opportunity costs, and patient anxiety," stated senior author Diana Miglioretti, PhD, Professor and Division Chief of Biostatistics at the UC Davis Department of Public Health Sciences at UC Davis Comprehensive Cancer Center.