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Data from two phase 2 studies suggests single-agent blinatumomab produces similar outcomes in adults with relapsed/refractory acute lymphoblastic leukemia (ALL), regardless of age.
Patients age 65 and older had similar hematologic response rates and relapse-free survival rates as patients younger than 65.
The incidence of grade 3 or higher adverse events (AEs) was similar between the age groups as well.
Older patients did have more serious AEs, however. And they had more neurologic events, but these were reversible.
Hagop M. Kantarjian, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in Cancer. The research was funded by Amgen Inc., makers of blinatumomab.
Patients
The researchers examined 261 adults with relapsed/refractory ALL who were enrolled in 2 different studies. There were 36 patients who were 65 or older and 225 patients who were younger than 65. The median ages were 70 (range, 65-79) and 34 (range, 18-64), respectively.
Among the older patients, 14% had primary refractory disease, 67% had 1 prior relapse, 14% had 2 prior relapses, and 6% had 3 or more. Among the younger patients, 9% had primary refractory disease, 55% had 1 prior relapse, 26% had 2 prior relapses, and 10% had 3 or more.
The younger patients were more likely to have received an allogeneic hematopoietic stem cell transplant (allo-HSCT) than the older patients—37% and 11%, respectively.
But older patients were more likely to have mild renal impairment (42% vs 13%) or moderate renal impairment (22% vs 1%).
Treatment
All patients received blinatumomab, and stepwise dosing was used to reduce the risk of cytokine release syndrome. A treatment cycle consisted of 4 weeks of continuous intravenous infusions, followed by a 2-week treatment-free interval.
The patients received 2 initial cycles. If they achieved a complete remission (CR) or CR with partial hematologic recovery (CRh) at this point, they could receive an additional 3 cycles as consolidation, unless they were scheduled to receive an allo-HSCT.
Patients also received intrathecal prophylaxis with dexamethasone and/or steroids, cytarabine, and methotrexate. And patients with a high blast percentage at baseline received a pre-phase treatment with dexamethasone and/or cyclophosphamide.
Older patients received a median of 2 cycles of blinatumomab (range, 1-6), as did the younger patients (range, 1-7).
Response and survival
Fifty-six percent of the older patients (20/36) achieved a CR/CRh during the first 2 cycles of blinatumomab, as did 46% of the younger patients (46/225). There were 14 CRs among the older patients (39%) and 78 CRs among the younger patients (35%).
There were 12 complete minimal residual disease responses among older patients (60% of responders) and 73 among the younger patients (70% of responders).
Of the responders, 3 older patients (15%) and 61 younger patients (59%) went on to allo-HSCT. Most of the patients received a transplant while in remission. However, 1 of the older patients and 8 of the younger patients went to transplant after an initial response to blinatumomab that was followed by a relapse.
The median relapse-free survival was 7.4 months for both age groups. The median overall survival was 5.5 months for older patients and 7.6 months for younger patients.
Safety
All of the older patients had at least 1 AE, and all but 1 of the younger patients had at least 1 AE. Older patients had higher rates of peripheral edema (42% vs 24%), fatigue (28% vs 18%), and dizziness (25% vs 11%) of any grade.
The incidence of grade 3 or higher AEs was similar between the groups—86% in the older group and 80% in the younger group. The same was true for AEs leading to treatment discontinuation—22% and 19%, respectively.
However, there was a higher incidence of serious AEs in the older patients (72% vs 64%). Device-related infection and encephalopathy were more common among older patients than younger patients (both 11% vs 3%).
The incidence of cytokine release syndrome was higher in the older group than the younger group—19% and 10%, respectively.
Older patients also had more neurologic events of any grade (72% vs 48%) and more grade 3 or higher neurologic events (28% vs 13%). However, all neurologic events were reversed by temporarily or permanently discontinuing blinatumomab.
There were 7 fatal treatment-emergent AEs in the older adults, including pneumonia (n=3), B-cell lymphoma (n=1), and disease progression (n=3). None of the fatal AEs were considered treatment-related. And none of the patients who were in remission died during treatment with blinatumomab.
