In a new study, researchers said they were surprised when a review of first-line chronic lymphocytic leukemia treatment showed racial disparities within the VA healthcare system, which is known for providing equitable care. Black veterans were found to be less likely to receive early novel agents to treat CLL compared to white ones. The situation improved over time, however, and survival rates did not appear to be affected.
SAN ANTONIO — Black patients diagnosed with chronic lymphocytic leukemia (CLL) in the VA healthcare system were less likely to receive early novel agents (NAs) to treat their cancer, compared to white patients, according to a new study.
The report in the Journal of Managed Care Specialty Pharmacy pointed out that ibrutinib, idelalisib and venetoclax were first introduced in 2013 as therapeutic options to treat CLL. A study team led by researchers from the South Texas Veterans Healthcare System and the University of Texas Health, both in San Antonio, sought to determine whether the uptake of NAs for first-line treatment was similar across races.1
“Among Black patients, the higher prevalence of high-risk features for which NAs are recommended might predict a higher rate of novel treatment receipt compared with white patients,” the authors wrote. “The Veterans Affairs (VA) is the largest equal-access health care system in the United States, so it is expected that VA patients should have equal access to these NAs. We hypothesized that the uptake of NAs for first-line treatment of CLL would be similar in Black and white patients managed in the VA.”
The study team conducted a retrospective cohort study including adults with CLL managed in the VA from Oct. 1, 2013, to Sept. 30, 2017. Included in the study were 565 patients—86% white and 14% Black. Black patients were younger than White patients (median age [66 vs. 69 years; P < 0.01]) but had similar median baseline Charlson comorbidity scores (4 vs. 5).
Results indicated that, overall, Black patients were less likely to receive NAs than white patients (14% vs. 26%; P = 0.02), although the gap narrowed over the study period:
- 4% vs. 17% (2014),
- 13% vs. 25% (2015),
- 17% vs. 33% (2016), and
- 31% vs. 33% (2017).
“Black race (P = 0.02) and fiscal year (P < 0.01) were the only variables significantly associated with NA use in the multivariable model,” the researchers pointed out. “Health outcomes and most complications were similar for Black and white patients despite the difference in prescribing patterns.”
CLL, the most common leukemia in adults, also has a significant impact on the health of many U.S. veterans. Since 1993, more than 27,000 veterans have received care for CLL through the VA, at least partly because the U.S. veteran population has a high proportion of CLL risk factors.
In a 2002 report, the Health and Medicine Division (HMD) (formerly known as the Institute of Medicine) of the National Academy of Sciences, Engineering, and Medicine concluded there is sufficient evidence of an association between exposure to herbicides and CLL. In 2003, VA recognized CLL as related to exposure to Agent Orange or other herbicides during military service, according to the VA.
In an updated 2008 report, HMD wrote there is sufficient evidence of an association between exposure to Agent Orange and CLL, including hairy cell leukemia and other chronic B-cell leukemias. As a result, VA expanded CLL to include all chronic B-cell leukemias as related to exposure to Agent Orange or other herbicides during military service. VA’s final ruling on this association took effect on Oct. 30, 2010.
Mitigating Disparities
The authors of the study showing treatment disparity advised, “Managed care providers should consider racial, socioeconomic, and cultural factors that may drive disparities, such as these, so that they can design and implement strategies to prevent and mitigate these disparities.”
While CLL has a median age of diagnosis of 70 years and older white males have the greatest incidence, Black males also are at risk and tend to be diagnosed at a younger age—mean age at diagnosis of 67 vs. 70 years).
“Although survival rates have improved overall, outcomes in CLL demonstrate inferior survival among Black patients, with a 5-year survival rate of only 64%,” according to the authors, who noted that the overall survival rate is greater than 80%. “Black patients have also presented with factors associated with worse outcomes, including lower median hemoglobin levels, higher β2-microglobulin levels, and more unmutated IGHV gene expression, ZAP70 expression, and chromosome 17p or 11q deletion.”
The authors advised that treatment options have expanded since the period involved in their study, explaining, “With regard to CLL, the ‘NAs’ ibrutinib (Bruton tyrosine kinase inhibitor, US Food and Drug Association-approved for CLL in February 2014), idelalisib (PI3 kinase inhibitor, July 2014), and venetoclax (BCL-2 inhibitor, April 2016) function at the gateway of dysregulated enzyme pathways. Randomized clinical trials, including RESONATE (relapsed/refractory ibrutinib) and RESONATE-2 (first-line ibrutinib), have demonstrated the ability of ibrutinib to improve survival compared with chemotherapy (CT)-based treatments. A follow-up 6-year analysis of the RESONATE trial reported statistically significant improvement in progression-free survival, overall survival, and overall response rate with ibrutinib. Importantly, these NAs are available as oral therapies, as opposed to traditional chemotherapies, most of which are intravenous only.”
The study noted that, for patients with high-risk disease (patients with del[17p], del[11q], unmutated IGHV, or mutated TP53), regardless of age and comorbidities, the use of NAs is recommended by clinical guidelines. “As the incidence of CLL increases, with an older, more diverse population undergoing treatment, use of NAs is expected to rise,” it added.
Within the VHA, according to VA Press Secretary Terrence Hayes, treatment options for CLL are determined by mutation status and the age of the patient. “Mostly, CLL is treated using oral BTK inhibitors indefinitely vs time dependent therapy which is a targeted oral pill and a CD20 monoclonal antibody for one year,” Hayes said in response to a U.S. Medicine question. “ If a patient is young and has a positive IgVH mutation, it is still recommended that they receive chemotherapy with the FCR regimen. Chemotherapy is not recommended in patients that carry a TP53 mutation, as the response rate is generally low.”
- Lucero KT, Obodozie-Ofoegbu OO, Nooruddin Z, Ryan K, Castillo A, Moore AM, Jones X, Frei CR. Health disparity in use of novel agents for first-line therapy in Black and White patients with chronic lymphocytic leukemia in the Department of Veterans Affairs. J Manag Care Spec Pharm. 2023 Apr;29(4):420-430. doi: 10.18553/jmcp.2023.29.4.420. PMID: 36989449.
