Contributions
Abstract: PB1643
Type: Publication Only
Background
Despite the significant advances in modern chemotherapy, it remains challenging to treat adult patients with acute lymphoblastic leukemia (ALL). The relapse rate continues to be high, and the outcome at the time of relapse is dismal. In this setting of patients, antibody-based therapies have demonstrated promising single-agent activity.
Aims
We aimed to describe our clinical experience in the sequential use of the bispecific T cell engager blinatumomab and the anti-CD22 antibody-drug conjugate inotuzumab ozoagamicin (IO) in relapsed/refractory B-cell precursor ALL (R/R B-ALL).
Methods
Adult patients with R/R B-ALL initially treated with blinatumomab and then moved to IO for disease reappearance were selected from the institutional database. Clinical data, diagnostic work-up, treatment modalities, and outcomes were extracted.
Results
We identified 3 R/R B-ALL patients who received blinatumomab for a bone marrow relapse after standard chemotherapy. At blinatumomab start, median age was 58 years, male/female ratio was 2:1 and median number of prior chemotherapy lines was 3 (2–4). At diagnosis all patients had a poor-risk disease: 2 patients were Philadelphia chromosome–positive (Ph+) ALL, while for the remaining one hyperleukocytosis was present at ALL onset and cytogenetic analysis reported 47,XXX [20].
Prior chemotherapies included Hyper-CVAD regimen and pediatric-type therapeutic program proposed by the Northern Italy Leukemia Group; both patients with Ph+ ALL had already been treated with all available tyrosine kinase inhibitors.
Blinatumomab was obtained through an expanded access use and given as continuous IV infusion at a dose of 28 μg/m2/d for 4 weeks, with a 2-week break. The median administered cycle number was 4 (2-5). For all patients complete morphological remission and cytofluorimetric negative minimal residual disease were achieved since the first cycle. Unfortunately, after a median time of 63 days 2 patients had a bone marrow relapse, one of these with CD19- lymphoblasts, while the remaining patient had an extramedullary relapse with lymph-nodes involvement. In all 3 cases blast cells showed CD22s expression by flow cytometry.
Only one patient experienced a G2 neurological toxicity which progressively improved with dexamethasone.
Expanded access use of IO was started for relapse after blinatumomab treatment. Patients received a combination of vincristine and prednisone to reduce the amount of ALL before IO start. Median time from blinatumomab interruption and IO was 55 days. Patients received IO IV at a dose of 1.8 mg/m2 for the first cycle and then 1.5 mg/m2, divided in three weekly doses, every 3-4 weeks for a median number of 2 cycles (1–4). Again, all 3 patients received complete morphological remission and cytofluorimetric negativity after the first cycle; for the only patient with lymph-node involvement a PET analysis demonstrated absence of active disease. IO was generally well tolerated; 2 patients had a G2 transaminases elevation. Two patients proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT); one of this died 4 months after allo-HSCT for ALL progression, while the other one is still alive and in ALL complete remission after 2 months from allo-HSCT. One patient was not candidate to allo-HSCT and we have planned to complete 6 IO cycles.
Conclusion
This monocentric survey underlined the feasibility and efficacy of sequential use of blinatumomab and IO in R/R B-ALL with the possibility to proceed safely to allo-HSCT.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Immunotherapy, Relapse
Abstract: PB1643
Type: Publication Only
Background
Despite the significant advances in modern chemotherapy, it remains challenging to treat adult patients with acute lymphoblastic leukemia (ALL). The relapse rate continues to be high, and the outcome at the time of relapse is dismal. In this setting of patients, antibody-based therapies have demonstrated promising single-agent activity.
Aims
We aimed to describe our clinical experience in the sequential use of the bispecific T cell engager blinatumomab and the anti-CD22 antibody-drug conjugate inotuzumab ozoagamicin (IO) in relapsed/refractory B-cell precursor ALL (R/R B-ALL).
Methods
Adult patients with R/R B-ALL initially treated with blinatumomab and then moved to IO for disease reappearance were selected from the institutional database. Clinical data, diagnostic work-up, treatment modalities, and outcomes were extracted.
Results
We identified 3 R/R B-ALL patients who received blinatumomab for a bone marrow relapse after standard chemotherapy. At blinatumomab start, median age was 58 years, male/female ratio was 2:1 and median number of prior chemotherapy lines was 3 (2–4). At diagnosis all patients had a poor-risk disease: 2 patients were Philadelphia chromosome–positive (Ph+) ALL, while for the remaining one hyperleukocytosis was present at ALL onset and cytogenetic analysis reported 47,XXX [20].
Prior chemotherapies included Hyper-CVAD regimen and pediatric-type therapeutic program proposed by the Northern Italy Leukemia Group; both patients with Ph+ ALL had already been treated with all available tyrosine kinase inhibitors.
Blinatumomab was obtained through an expanded access use and given as continuous IV infusion at a dose of 28 μg/m2/d for 4 weeks, with a 2-week break. The median administered cycle number was 4 (2-5). For all patients complete morphological remission and cytofluorimetric negative minimal residual disease were achieved since the first cycle. Unfortunately, after a median time of 63 days 2 patients had a bone marrow relapse, one of these with CD19- lymphoblasts, while the remaining patient had an extramedullary relapse with lymph-nodes involvement. In all 3 cases blast cells showed CD22s expression by flow cytometry.
Only one patient experienced a G2 neurological toxicity which progressively improved with dexamethasone.
Expanded access use of IO was started for relapse after blinatumomab treatment. Patients received a combination of vincristine and prednisone to reduce the amount of ALL before IO start. Median time from blinatumomab interruption and IO was 55 days. Patients received IO IV at a dose of 1.8 mg/m2 for the first cycle and then 1.5 mg/m2, divided in three weekly doses, every 3-4 weeks for a median number of 2 cycles (1–4). Again, all 3 patients received complete morphological remission and cytofluorimetric negativity after the first cycle; for the only patient with lymph-node involvement a PET analysis demonstrated absence of active disease. IO was generally well tolerated; 2 patients had a G2 transaminases elevation. Two patients proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT); one of this died 4 months after allo-HSCT for ALL progression, while the other one is still alive and in ALL complete remission after 2 months from allo-HSCT. One patient was not candidate to allo-HSCT and we have planned to complete 6 IO cycles.
Conclusion
This monocentric survey underlined the feasibility and efficacy of sequential use of blinatumomab and IO in R/R B-ALL with the possibility to proceed safely to allo-HSCT.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Immunotherapy, Relapse