Chijioke Nze, MD, MPH
Christopher R. Flowers, MD, MS, FASCO
In a single-institution study reported in the journal Cancer, and reviewed in the September 10, 2021, issue of The ASCO Post, Bei Hu, MD, and colleagues from Levine Cancer Institute/Atrium Health found that the use of a dedicated nurse navigation program aided in producing similar patterns of care and outcomes comparing minority patents and White patients with aggressive large B-cell lymphoma (LBCL), the most common non-Hodgkin lymphoma (NHL) subtype.1 NHL is the seventh most common cancer and the ninth leading cause of cancer death for both men and women in the United States. In 2021, an estimated 81,560 people in the United States will be diagnosed with NHL and 20,720 will die of the disease.2 Although the incidence of NHL in the United States has decreased and survival has improved in recent years,3 many disparities remain.4-10
Although differences in the incidence of lymphomas by race and ethnicity are well known,11 and many groups have contributed to a refined understanding of disparities in solid tumors, relatively few researchers have examined disparities in the presentation and outcomes for patients with lymphoma. Lymphoid cancer incidence rates are slightly (4%) lower among non-Hispanic Black individuals, 14% lower among Hispanics, and 42% lower among Asians/Pacific Islanders, compared with non-Hispanic Whites, and there is considerable variation by subtype. Notable disparities in survival have been described in LBCL and other lymphomas by race,12-17 insurance status,18-21 gender,14,22 socioeconomic status,23-25 and rural status.26 As an example, Black patients with LBCL are diagnosed at a mean age > 10 years younger than White patients, more commonly have advanced-stage disease, and are less likely to survive 5 years.15,17,27
In national statistics, other subtypes with notable survival differences by race include mycosis fungoides, peripheral T-cell lymphoma, and Burkitt lymphoma, and Black males have the lowest survival across lymphoid cancer subtypes.28 Future studies are needed to assess the relative contribution of biologic and individual factors to these disparities.
Database and Study Limitations
One of the major challenges in cancer health disparities research has been the reliance on data from population-based cancer registries. The Surveillance, Epidemiology, and End Results and National Cancer Database registries represent approximately 34% and 70% of the U.S. population, respectively.29,30 These registries collect data on cancer incidence and survival for specific geographic regions; they provide standardized data on tumor characteristics, patient demographics, and survival, but they typically do not contain specimens that allow in-depth genomic or biologic analysis of tumors.
“One of the major challenges in cancer health disparities research has been the reliance on data from population-based cancer registries.”— Chijioke Nze, MD, MPH, and Christopher R. Flowers, MD, MS, FASCO
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The study by Hu and colleagues involved prospectively collected data on 204 consecutive patients with LBCL, including 47 minority patients (Black/African American, Asian, Native American/Pacific Islander, and those of Hispanic/Latinx ethnicity) and 157 White patients, receiving initial treatment, treatment for relapse, or both at the Levine Cancer Institute central location between January 2016 and June 2019. Among the 204 patients, 186 had diffuse large B-cell lymphoma, 14 had primary mediastinal B-cell lymphoma, and 4 had high-grade B-cell lymphoma. Importantly, as in other studies, Hu and colleagues confirmed that double-hit lymphomas, revised International Prognostic Index score ≥ 3, and relapsed/refractory disease predicted worse survival. However, one of the challenges with interpreting these findings is that the study grouped patients across several minority groups together, included patients with various LBCL subtypes, and included newly diagnosed and relapsed patients.
Although assembling a single system study with sufficient numbers of patients for each minority group is challenging, we recognize that individual populations have distinctions in presentation of disease and outcomes. As an interesting example, a California Cancer Registry study examined ethnic subgroups that would all be classified as Asian in the Hu et al study (and most other studies) and found distinct patterns of lymphoma incidence and presentation across Asian subgroups.31-33 Other studies have examined genomic admixtures for patients with LBCL by Asian, European, and African ancestry and found that this also influences presentation and outcomes.34
Access to Treatment
It is clear that interventions such as patient navigation need to be customized to particular patient populations based on identified disparities by race, gender, age, insurance status, demographic location, socioeconomic status, and other characteristics. A full understanding of the value of such interventions for patients with lymphoma from underrepresented minority groups will require assessment of patient population–specific interventions.
The access to standard-of-care treatment options is a crucial lever of particular interest that was addressed by Hu and colleagues. A recent study found that Black patients with NHL are up to 38% less likely to undergo autologous stem cell transplantation (autoSCT) than their White counterparts, despite similar rates of relapse rates and first-line immunochemotherapy.35 While disparities have been described for patients who are Medicaid-insured and uninsured when diagnosed with LBCL,20 follicular lymphoma,18 and Burkitt lymphoma,19 no disparities were observed by insurance status for plasmablastic lymphoma, a disease for which there is little effective treatment.19 Together, these findings suggest that when similar treatments can be administered, similar outcomes can occur. This point has been confirmed by studies in the Veterans Administration single-payer system.36
Nurse Navigation Encounters
In the Hu et al study, all patients were discussed at a weekly multidisciplinary meeting attended by nursing staff, nurse navigator cellular therapy coordinators, oncology pharmacists, lymphoma faculty, and research staff. Nurse navigation encounters were characterized as low or high intensity.
Nurse navigation was used by > 80% of patients, and high-intensity navigation was used by 42% of minority vs 21% of White patients (P = .01), with median durations of encounters being 135 vs 60 minutes (P < .001) for high- vs low-intensity encounters. Minority patients more commonly used nurse navigation for assistance with compliance concerns (18% vs 7%), insurance questions (29% vs 8%), financial concerns (37% vs 18%), and transportation concerns (16% vs 2%).
It is of interest that although minority patients in the Hu et al study had a significantly higher rate of either Medicaid or no insurance than their non-Hispanic White counterparts (26 % vs 4%), they underwent autoSCT and chimeric antigen receptor T-cell therapy at identical rates. These interventions, considered to be efficacious second-line treatments after failure of initial therapy, often are particularly underutilized by socioeconomically disadvantaged patients. This highlights how various interventions, facilitated by nurse navigation, can overcome barriers that contribute to disparities such as insurance coverage.
Other studies have demonstrated the effectiveness of patient navigators to reduce disparities in access to cancer care and treatment, particularly for women and minority populations. For instance, the Enhancing Minority Participation in Clinical Trials (EMPaCT) Consortium, a National Cancer Institute (NCI)-funded project to increase minority participation in clinical trials at five NCI cancer centers, developed an evidenced-based training and implementation model for navigation.37-39
“These findings suggest that when similar treatments can be administered, similar outcomes can occur.”— Chijioke Nze, MD, MPH, and Christopher R. Flowers, MD, MS, FASCO
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Numerous factors influence disparities in survival for patients with lymphoid cancers. For example, Black patients with lymphoma are less likely to be insured,15,17,25,27 and uninsured patients with LBCL more commonly present with advanced-stage disease and comorbid illnesses and less commonly received standard treatment in the period when chemoimmunotherapy was first approved.20 Eliminating disparities in LBCL survival is multifaceted and must address complex interactions among social, environmental, biologic, and patient-centered factors.
Multilevel models have been developed to understand and address the biologic, environmental, and social/institutional factors associated with lymphoma disparities.40 As stated by the investigators, “Aggressive … LBCLs are curable, but previous studies have shown inferior outcomes in minorities. Nurse navigation programs can improve patient outcomes by providing patient support. This study presents the outcomes of White and minority patients with aggressive LBCL at an institution with an active nurse navigation program.” Together, these data suggest that effective interventions can be implemented to address identified disparities in outcomes for patients with lymphoma.
DISCLOSURE: Dr. Nze reported no conflicts of interest. Dr. Flowers has served as a consultant for AbbVie, AstraZeneca, Bayer, BeiGene, Bristol Meyers Sqibb/Celgene Corporation, Denovo Biopharma LLC, Genentech/Roche Pharma, Genmab, Gilead Sciences, Karyopharm Therapeutics, Morphosys AG, Pharmacyclics/Janssen Pharmaceuticals, Seagen, and Spectrum Pharmaceuticals; has received institutional research funding from 4D, AbbVie, Acerta Pharma, LLC, Adaptimmune, Allogene Therapeutics, Amgen, Bayer, Celgene Corporation, Cellectis, EMD, Gilead Sciences, Genentech/Roche Pharma, Guardant, Iovance Biotherapeutics, Janssen Pharmaceuticals, Kite Pharma, MorphoSys AG, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda Pharmaceutical Company, TG Therapeutics, Xencor, Ziopharm, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, National Cancer Institute, V Foundation for Cancer Research, and the Cancer Prevention and Research Institute of Texas, where he is a CPRIT Scholar in Cancer Research.
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Dr. Nze is a hematology/oncology fellow and Dr. Flowers is Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, Houston.