Contributions
Abstract: PB1379
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Clinical
Background
Adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-cell ALL) have a dismal prognosis and a high mortality rate. The advent of new targeted therapies has led to higher rates of complete remission (CR), prolonged the overall survival (OS) and increased the likelihood of proceeding to allogeneic hematopoietic stem cell transplantation (HSCT).
Blinatumomab is a bispecific T cell-engaging antibody that binds CD3-positive T cells to CD19-positive lymphoblasts leading to the lysis of both malignant and normal B cells. The mechanisms of resistance remain unclear, but the occurence of extramedullary relapse, the loss of CD19 expression and a high disease burden are described as potential predictive factors for a poor response.
Aims
To describe patient characteristics, analyze outcomes, including the CR rate, OS and the proportion of patients who subsequently underwent allogeneic HSCT and review the tolerability of the drug.
Methods
This is a retrospective analysis of 10 patients with R/R B-cell ALL, with a median age of 29 (18-50) years, treated with blinatumomab between January 2019 and December 2020 at Fundeni Clinical Institute. Survival rates were calculated using the Kaplan-Meier method, adjusting for key patient demographic and clinical characteristics at baseline.
Results
Four patients (40%) had combined medullary and extramedullary localization – bone/lymph node/spleen. The median tumor burden before treatment was 45% blast cells (0.1 – 80%). The median number of previous salvage therapies was 1.7 (1-3).
The rate of CR was 40% (N=4) after the first cycle of blinatumomab. Among the responders, 50% (N=2) went on to receive allogeneic HSCT, and the remaining two patients relapsed before they could proceed to HSCT. All of the patients with high tumor burden received prephase therapy consisting of dexamethasone and, in selected cases, cyclophosphamide. The response rate was higher in patients with lower tumor burden compared with those with more than 50% blasts. The median OS was 5.2 months, and for those patients who achieved CR, the median RFS was 4.5 months, with a median follow-up of 9.8 months.
The treatment was generally well tolerated. All patients experienced adverse events, the most common being fever (90%, 9 patients). One of the patients developed disseminated intravascular coagulation as well as grade 3 cytokine release syndrome, leading to treatment discontinuation; one patient had grade 2 mandibular pain, which required opiod analgesia and one patient had a prolonged fever that lasted almost 3 weeks.
Conclusion
The rate of CR and the percentage of patients who underwent allogeneic HSCT following treatment with blinatumomab are similar to those reported previously. The RFS and OS rates are lower than the existing literature data. Along with previous studies, the current work highlights the existence of a subgroup of patients with poor response to blinatumomab monoterapy, which remains a major challenge in clinical practice.
Keyword(s): Acute lymphoblastic leukemia, Targeted therapy
Abstract: PB1379
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Clinical
Background
Adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-cell ALL) have a dismal prognosis and a high mortality rate. The advent of new targeted therapies has led to higher rates of complete remission (CR), prolonged the overall survival (OS) and increased the likelihood of proceeding to allogeneic hematopoietic stem cell transplantation (HSCT).
Blinatumomab is a bispecific T cell-engaging antibody that binds CD3-positive T cells to CD19-positive lymphoblasts leading to the lysis of both malignant and normal B cells. The mechanisms of resistance remain unclear, but the occurence of extramedullary relapse, the loss of CD19 expression and a high disease burden are described as potential predictive factors for a poor response.
Aims
To describe patient characteristics, analyze outcomes, including the CR rate, OS and the proportion of patients who subsequently underwent allogeneic HSCT and review the tolerability of the drug.
Methods
This is a retrospective analysis of 10 patients with R/R B-cell ALL, with a median age of 29 (18-50) years, treated with blinatumomab between January 2019 and December 2020 at Fundeni Clinical Institute. Survival rates were calculated using the Kaplan-Meier method, adjusting for key patient demographic and clinical characteristics at baseline.
Results
Four patients (40%) had combined medullary and extramedullary localization – bone/lymph node/spleen. The median tumor burden before treatment was 45% blast cells (0.1 – 80%). The median number of previous salvage therapies was 1.7 (1-3).
The rate of CR was 40% (N=4) after the first cycle of blinatumomab. Among the responders, 50% (N=2) went on to receive allogeneic HSCT, and the remaining two patients relapsed before they could proceed to HSCT. All of the patients with high tumor burden received prephase therapy consisting of dexamethasone and, in selected cases, cyclophosphamide. The response rate was higher in patients with lower tumor burden compared with those with more than 50% blasts. The median OS was 5.2 months, and for those patients who achieved CR, the median RFS was 4.5 months, with a median follow-up of 9.8 months.
The treatment was generally well tolerated. All patients experienced adverse events, the most common being fever (90%, 9 patients). One of the patients developed disseminated intravascular coagulation as well as grade 3 cytokine release syndrome, leading to treatment discontinuation; one patient had grade 2 mandibular pain, which required opiod analgesia and one patient had a prolonged fever that lasted almost 3 weeks.
Conclusion
The rate of CR and the percentage of patients who underwent allogeneic HSCT following treatment with blinatumomab are similar to those reported previously. The RFS and OS rates are lower than the existing literature data. Along with previous studies, the current work highlights the existence of a subgroup of patients with poor response to blinatumomab monoterapy, which remains a major challenge in clinical practice.
Keyword(s): Acute lymphoblastic leukemia, Targeted therapy