Take-aways:
- Induction and consolidation therapy with the anti-CD19 bispecific T-cell engager antibody construct blinatumomab as monotherapy was well tolerated in older patients with newly diagnosed Ph–negative B-cell ALL.
- The complete response rate was 66%, even among patients with high-risk cytogenetics, and 3-year survival rates reached 37%.
- The chemotherapy-free approach of blinatumomab monotherapy could represent a promising therapy for older adults who cannot tolerate standard intensive combination chemotherapy.
A chemotherapy-free approach with blinatumomab as induction and consolidation led to promising survival outcomes in older patients with Philadelphia chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (B-ALL), according to results from the SWOG 1318 trial. The findings were published in the Journal of Clinical Oncology by Anjali S. Advani, MD, from Cleveland Clinic’s Taussig Cancer Institute, and colleagues.
The prognosis for this patient population remains poor and older adults have been difficult to treat with standard intensive combination chemotherapy, Dr. Advani explained. CD19 is expressed on most precursor B-ALL cells and represents an attractive therapeutic target. “The anti-CD19 bispecific T-cell engager antibody construct blinatumomab has demonstrated significant activity in both relapsed/refractory ALL and measurable residual disease [MRD]–positive B-ALL,” they wrote. The SWOG 1318 trial, therefore, evaluated blinatumomab as a single agent in the upfront treatment of older patients with newly diagnosed Ph–negative B-ALL.
The trial enrolled patients ages 65 or older with newly diagnosed B-ALL who were treated at National Clinical Trial Network sites from June 2015 to September 2017.
Patients received blinatumomab for induction for 1 or 2 cycles until attainment of complete remission (CR) or CR with incomplete count recovery (CRi). During induction, blinatumomab was administered at doses of 9 mcg once daily on days 1 through 7 and 28 mcg once daily on days 8 through 28. During reinduction and post-remission therapy, blinatumomab was administered at a dose of 28 mcg once daily on days 1 through 28, followed by 18 months of maintenance POMP chemotherapy (prednisone, vincristine, 6-mercaptopurine, and methotrexate).
Per study protocol, patients received dexamethasone once before each cycle—20 mg intravenous 1 hour before the start of blinatumomab for each cycle and before day 8 of cycle 1 when the blinatumomab dose was escalated. Doses of intrathecal methotrexate were administered as central nervous system prophylaxis every 4 to 6 weeks for a total of 8 doses.
The present analysis looked at outcomes among 29 eligible patients (median age, 75; range, 66-84). Most patients had standard cytogenetic risk (55%), while 34% had poor-risk disease.
The most common grade 3/4 treatment-related nonhematologic adverse events (AEs) included:
- hyperglycemia (n, 4/29; 14%)
- dyspnea (n, 3/29; 10%)
- febrile neutropenia (n, 3/29; 10%)
- hypertension (n, 3/29; 10%)
- lung infection (n, 2/29; 7%)
One patient developed grade 3 cytokine release syndrome, and another developed grade 3 neurotoxicity, both instances were considered related to treatment.
No patients died during the first 28 days of treatment, but 1 patient died 34 days after beginning induction therapy. This patient died of respiratory failure, with B-ALL contributory and joint infection possibly contributory, the authors reported.
The overall response rate (CR + CRi) was 66% (n, 19), which was not significantly different between patients with poor-risk cytogenetics (70%) or other cytogenetic risk groups (59%). Among the 13 responding patients who were evaluable for MRD, 12 (92%) achieved MRD negativity.
During a median follow-up of 3.14 years, the 3-year overall survival (OS) and disease-free survival estimates were 37% (Figure 1). The median OS for poor-risk versus other cytogenetic risk groups was 1.33 years and 2.48 years, respectively. The median OS for patients younger than 75 years versus 75 or older was 2.61 years and 1.94 years, respectively, the researchers noted.
“The advantage of this treatment was the very limited toxicity (no deaths in the first month), and the OS was encouraging as compared with historical controls,” wrote Dr. Advani and colleagues. While they acknowledge that the small study population was a limitation, it “was performed within a cooperative group setting, thus illustrating the generalizability of such an approach.”
Despite the promising response and survival rates, they noted that the high rate of CD19-negative relapses as an area of future investigation. “[This finding] suggests that sequencing other agents (ie, targeting CD22) may be beneficial,” the researchers wrote. Current approaches under investigation include sequencing blinatumomab and inotuzumab and combining inotuzumab with mini-hyper–cyclophosphamide, vincristine, dexamethasone plus blinatumomab.
“In the future, treatment is likely to include combinations of multiple novel agents, but clinical trials will be needed to determine the best approach for each subset of patients,” the authors concluded. “We may be moving toward largely chemotherapy-free approaches in older patients with ALL, as is already the case for acute promyelocytic leukemia.”
Disclosures: This research was supported by the National Cancer Institute. Study authors report financial relationships with Amgen, the manufacturer of blinatumomab.
Reference
Advani AS, Moseley A, O’Dwyer KM, et al. SWOG 1318: A phase II trial of blinatumomab followed by POMP maintenance in older patients with newly diagnosed Philadelphia chromosome–negative B-cell acute lymphoblastic leukemia. J Clin Oncol. 2022 Feb 14; doi: 10.1200/JCO.21.01766.