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Credit: ASCO/Scott Morgan
CHICAGO—A new monoclonal antibody, blinatumomab, achieves an “exceptionally high complete remission rate” as a single agent in acute lymphoblastic leukemia (ALL), according to investigators.
They reported that about 70% of adult patients with relapsed/refractory B-precursor ALL achieved a hematologic complete remission (CR).
Max Topp, MD, of the Wuerzburg University Medical Center in Germany, presented the findings as abstract 6500 at the 2012 ASCO Annual Meeting held here recently.
Outcomes are poor for adult patients with relapsed/refractory ALL following frontline therapy. Several clinical trials have shown that most patients fail to achieve CR. Response rates are typically 20% to 30%.
“Treatment-related mortality is high, CR is not durable, and overall survival is dismal at a median of 4-6 months after relapse,” Dr Topp said. “[A]llogeneic stem cell transplant (alloSCT) is only really available to patients who reach a CR, and few patients make it to SCT.”
After alloSCT, the overall survival rate at 1 year is about 20%, regardless of CR status. “There is a need for something completely different,” Dr Topp said.
Enter blinatumomab. Blinatumomab is a bispecific T-cell engaging antibody that directs cytotoxic T cells to CD19-expressing target cells.
Dr Topp and colleagues designed an open-label, multicenter, exploratory phase 2 study and enrolled 36 relapsed/refractory ALL patients. The patients were a median age of 31 years and had a high blast count. Some 40% had relapsed after alloSCT.
Patients received blinatumomab by continuous intravenous infusion for 4 weeks, with 2 weeks off, for up to 5 cycles. The investigators determined the safest dose to be 5 µg/m²/day in week 1, followed by 15 µg/m²/day for the remaining treatment. Twenty-three patients entered the extension phase at this dose.
Of the 36 patients enrolled, 26 (72%) achieved a hematologic CR, as did 17 of 23 patients (74%) in the extension phase.
The duration of hematologic CR was 8.9 months after a median observation time of 4.5 months.
Median overall survival was 9 months after a median follow-up of 10.7 months. This compares favorably with historical data, Dr Topp pointed out.
“Most importantly,” he added, “almost every patient who achieved CR had a molecular remission. Only 2 out of 26 patients didn’t reach this endpoint.”
He noted that 13 patients who reached CR had an alloSCT.
Early on, several patients developed cytokine release syndrome. So the researchers developed a prevention strategy of giving corticosteroids upfront. As a result, there were no cases of cytokine release syndrome in the extension phase.
The most common adverse events in the safest dosing schedule were pyrexia and headache. There were few grade 3 events, and all adverse events were reversible.
Dr Topp said the data support further investigation of blinatumomab in adult patients with relapsed/refractory ALL.
He noted that a global phase 2 study in this setting has already been initiated in the United States and Europe. 
Credit: ASCO/Scott Morgan
CHICAGO—A new monoclonal antibody, blinatumomab, achieves an “exceptionally high complete remission rate” as a single agent in acute lymphoblastic leukemia (ALL), according to investigators.
They reported that about 70% of adult patients with relapsed/refractory B-precursor ALL achieved a hematologic complete remission (CR).
Max Topp, MD, of the Wuerzburg University Medical Center in Germany, presented the findings as abstract 6500 at the 2012 ASCO Annual Meeting held here recently.
Outcomes are poor for adult patients with relapsed/refractory ALL following frontline therapy. Several clinical trials have shown that most patients fail to achieve CR. Response rates are typically 20% to 30%.
“Treatment-related mortality is high, CR is not durable, and overall survival is dismal at a median of 4-6 months after relapse,” Dr Topp said. “[A]llogeneic stem cell transplant (alloSCT) is only really available to patients who reach a CR, and few patients make it to SCT.”
After alloSCT, the overall survival rate at 1 year is about 20%, regardless of CR status. “There is a need for something completely different,” Dr Topp said.
Enter blinatumomab. Blinatumomab is a bispecific T-cell engaging antibody that directs cytotoxic T cells to CD19-expressing target cells.
Dr Topp and colleagues designed an open-label, multicenter, exploratory phase 2 study and enrolled 36 relapsed/refractory ALL patients. The patients were a median age of 31 years and had a high blast count. Some 40% had relapsed after alloSCT.
Patients received blinatumomab by continuous intravenous infusion for 4 weeks, with 2 weeks off, for up to 5 cycles. The investigators determined the safest dose to be 5 µg/m²/day in week 1, followed by 15 µg/m²/day for the remaining treatment. Twenty-three patients entered the extension phase at this dose.
Of the 36 patients enrolled, 26 (72%) achieved a hematologic CR, as did 17 of 23 patients (74%) in the extension phase.
The duration of hematologic CR was 8.9 months after a median observation time of 4.5 months.
Median overall survival was 9 months after a median follow-up of 10.7 months. This compares favorably with historical data, Dr Topp pointed out.
“Most importantly,” he added, “almost every patient who achieved CR had a molecular remission. Only 2 out of 26 patients didn’t reach this endpoint.”
He noted that 13 patients who reached CR had an alloSCT.
Early on, several patients developed cytokine release syndrome. So the researchers developed a prevention strategy of giving corticosteroids upfront. As a result, there were no cases of cytokine release syndrome in the extension phase.
The most common adverse events in the safest dosing schedule were pyrexia and headache. There were few grade 3 events, and all adverse events were reversible.
Dr Topp said the data support further investigation of blinatumomab in adult patients with relapsed/refractory ALL.
He noted that a global phase 2 study in this setting has already been initiated in the United States and Europe.
Credit: ASCO/Scott Morgan
CHICAGO—A new monoclonal antibody, blinatumomab, achieves an “exceptionally high complete remission rate” as a single agent in acute lymphoblastic leukemia (ALL), according to investigators.
They reported that about 70% of adult patients with relapsed/refractory B-precursor ALL achieved a hematologic complete remission (CR).
Max Topp, MD, of the Wuerzburg University Medical Center in Germany, presented the findings as abstract 6500 at the 2012 ASCO Annual Meeting held here recently.
Outcomes are poor for adult patients with relapsed/refractory ALL following frontline therapy. Several clinical trials have shown that most patients fail to achieve CR. Response rates are typically 20% to 30%.
“Treatment-related mortality is high, CR is not durable, and overall survival is dismal at a median of 4-6 months after relapse,” Dr Topp said. “[A]llogeneic stem cell transplant (alloSCT) is only really available to patients who reach a CR, and few patients make it to SCT.”
After alloSCT, the overall survival rate at 1 year is about 20%, regardless of CR status. “There is a need for something completely different,” Dr Topp said.
Enter blinatumomab. Blinatumomab is a bispecific T-cell engaging antibody that directs cytotoxic T cells to CD19-expressing target cells.
Dr Topp and colleagues designed an open-label, multicenter, exploratory phase 2 study and enrolled 36 relapsed/refractory ALL patients. The patients were a median age of 31 years and had a high blast count. Some 40% had relapsed after alloSCT.
Patients received blinatumomab by continuous intravenous infusion for 4 weeks, with 2 weeks off, for up to 5 cycles. The investigators determined the safest dose to be 5 µg/m²/day in week 1, followed by 15 µg/m²/day for the remaining treatment. Twenty-three patients entered the extension phase at this dose.
Of the 36 patients enrolled, 26 (72%) achieved a hematologic CR, as did 17 of 23 patients (74%) in the extension phase.
The duration of hematologic CR was 8.9 months after a median observation time of 4.5 months.
Median overall survival was 9 months after a median follow-up of 10.7 months. This compares favorably with historical data, Dr Topp pointed out.
“Most importantly,” he added, “almost every patient who achieved CR had a molecular remission. Only 2 out of 26 patients didn’t reach this endpoint.”
He noted that 13 patients who reached CR had an alloSCT.
Early on, several patients developed cytokine release syndrome. So the researchers developed a prevention strategy of giving corticosteroids upfront. As a result, there were no cases of cytokine release syndrome in the extension phase.
The most common adverse events in the safest dosing schedule were pyrexia and headache. There were few grade 3 events, and all adverse events were reversible.
Dr Topp said the data support further investigation of blinatumomab in adult patients with relapsed/refractory ALL.
He noted that a global phase 2 study in this setting has already been initiated in the United States and Europe.