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Blinatumomab safe, effective for older patients with relapsed, refractory ALL
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Blinatumomab appeared as safe and effective in older patients as it did in younger patients with relapsed and refractory B-precursor acute lymphoblastic leukemia, according to the results of two phase 2 studies.
Older patients experienced more neurologic adverse events than younger patients; however, most were reversible with treatment interruption, results showed.
“The treatment of older patients with B-precursor ALL remains a significant clinical challenge because, in addition to age, older patients have a higher prevalence of poor prognostic factors (eg, Philadelphia chromosome-positive disease),” Hagop M. Kantarjian, MD, professor and chair of the department of leukemia and associate vice president for global academic programs at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “Based on studies in patients aged 50 years to 92 years, older adults generally have a lower tolerance for conventional chemotherapy compared with younger patients, which can result in reduced dose intensity, lower response rates (58% to 85%), shorter response durations, a higher incidence and more pronounced severities of toxicities, and reduced quality of life.”
Blinatumomab (Blincyto, Amgen) is a bispecific T-cell engager antibody construct designed to direct cytotoxic T cells to CD19–expressing B cells.
Kantarjian and colleagues conducted a dose-finding study, followed by a confirmation study, to examine the safety and efficacy of blinatumomab for patients aged 65 years or older with relapsed and refractory ALL.
The results of the dose-finding study showed that 69% of patients achieved complete remission or complete remission with partial hematologic recovery, and 88% of responders experienced minimal residual disease response.
The confirmation study included data from 261 patients ( 65 years, n = 36; < 65 years, n = 225) assigned to continuous infusion of blinatumomab in 4-week cycles, followed by a treatment-free interval of 2 weeks.
The study dosage was 9 g per day during the first week of the cycle, followed by 28 g per day in subsequent weeks.
The rates of complete remission or complete remission with partial hematologic recovery during the first two treatment cycles served as the primary endpoint. Key secondary endpoints included RFS, OS, allogeneic hematopoietic stem cell transplantation after blinatumomab-induced remission, and adverse events.
During the initial two cycles, 20 older adults (56%; 95% CI, 38-72) and 104 younger adults (46%; 95% CI, 40-53) achieved complete remission ( 65 years, n = 14; < 65 years, n = 78) or complete remission with partial hematologic recovery ( 65 years, n = 6; < 65 years, n = 26).
Twelve older adults (60%; 95% CI, 36-81) and 73 younger adults (70%; 95% CI, 60-79) experienced a complete minimal residual disease response, whereas three older patients (15%) and 61 younger patients (59%) proceeded to HSCT.
Older adults had a median RFS of 7.4 months (95% CI, 2.7-23.1) and a median OS of 5.5 months (95% CI, 4.2-13.5). Among younger adults, median RFS was 7.4 months (95% CI, 6.1-9) and median OS was 7.6 months (95% CI, 5.8-8.6).
Although younger and older adults had similar types and incidences of adverse events, a greater proportion of older adults experienced peripheral edema (42% vs. 24%), fatigue (28% vs. 18%) and dizziness (25% vs. 11%).
Older and younger adults demonstrated similar rates of grade 3 or worse adverse events (86% vs. 80%) and infections (39% vs. 34%). The two cohorts discontinued treatment due to severe adverse events at roughly similar rates (22% vs. 19%).
A greater proportion of older patients experienced cytokine release syndrome (19% vs. 10%) and neurologic adverse events (any grade, 72% vs. 48%; grade 3, 28% vs. 13%). An ad hoc analysis showed an association between older age and increased risk for neurologic events (OR = 1.01; 95% CI, 1-1.03). The odds of a neurologic event increased by 1.8% for every 1-year increase in age.
All neurologic events reversed with temporary or permanent treatment discontinuation. Among 21 patients ( 65 years, n = 7; < 65 years, n = 14) who discontinued treatment to resolve neurologic events, six older adults and 11 younger adults eventually reinitiated treatment with blinatumomab.
“The data support the continued evaluation of single-agent immunotherapy with blinatumomab for the treatment of older adults with relapsed and refractory ALL, a population with a poor prognosis and limited treatment options,” Kantarjian and colleagues wrote. – by Cameron Kelsall
Disclosure: Amgen funded this study. Kantarjian reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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