Contributions
Abstract: EP367
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Persistent or recurrent measurable residual disease (MRD) is associated with high rates of relapse in B-cell acute lymphoblastic leukemia (ALL). We evaluated the CD3-CD19 bispecific T-cell engaging antibody, blinatumomab, in patient (pts) with B-cell ALL in complete remission (CR) who did not achieve MRD negativity with standard therapy or who experienced MRD relapse.
Aims
We evaluated the efficacy and safety of blinatumomab in pts with B-cell ALL and MRD-positive disease.
Methods
This is a single-arm, phase II trial of pts with B-cell ALL in CR who did not achieve MRD negativity or had MRD relapse after at least 3 months of frontline therapy (i.e. CR1) or after at least 1 month of salvage therapy (i.e. CR2 and beyond). Positive MRD was defined as ≥0.01% by flow cytometry in pts with Philadelphia chromosome (Ph)-negative ALL and a BCR-ABL1/ABL1 transcript ratio by PCR of ≥0.01% for pts with Ph-positive ALL. MRD negativity was defined as undetectable MRD by flow and PCR at a sensitivity of 10-4. Blinatumomab was given at standard doses (up to 28 µg/day, if tolerated) in 42-day cycles for up to 5 total consolidation cycles. Pts who did not proceed with ASCT could receive blinatumomab maintenance with one cycle every 3 months for up to 4 maintenance cycles (9 cycles total). A TKI of the treating physician's choice was added to the regimen for pts with Ph-positive ALL.
Results
Between 12/2015 and 2/2021, 31 pts with MRD-positive B-cell ALL in CR were enrolled. The median age was 42 years (range, 22-84 years). Thirteen pts (42%) had Ph-positive ALL; 10 pts received concomitant ponatinib, 2 received dasatinib, and 1 received imatinib. Twenty-three pts (74%) were in CR1, and 8 (26%) were in CR2 and beyond (5 in CR2 and 3 in CR3). Nineteen pts (61%) had persistent MRD and 12 (39%) had MRD relapse. Two pts had undergone prior ASCT.
Pts received a median of 3 cycles of blinatumomab consolidation (range, 1-5 cycles). Overall, 23 pts (74%) achieved MRD negativity at any time. Fifteen of 18 pts (83%) with Ph-negative ALL achieved MRD negativity, and 8 of 13 pts (62%) with Ph-positive ALL achieved MRD negativity. Three additional pts with Ph-positive ALL achieved a major molecular response as best response. Among the 23 MRD responders, 21 (91%) responded after 1 cycle; 1 after 2 cycles, and 1 after 4 cycles. MRD response occurred in 65% of pts in CR1 and 100% in CR2+. Eight pts (35% of MRD responders) proceeded to ASCT (5 in CR1 and 3 in CR2+) with median time to ASCT of 3 months (range, 2-6 months).
Blinatumomab-related adverse events were as expected, with adverse events of any grade observed in 12 pts (39%). All resolved with supportive management. One pt discontinued blinatumomab due to adverse event (grade 3 altered mental status). There were no grade 4 or 5 adverse events.
With a median follow-up of 25 months (range, 5-60 months), 7 pts have relapsed (30% of MRD responders). One relapse was in a pt who underwent ASCT and 6 were in pts who did not undergo ASCT (3 in CR1, 2 in CR2, and 1 in CR3). Four relapses were hematologic only, 1 was hematologic plus CNS, 1 was extramedullary only, and 1 was MRD only. The 3-year overall survival (OS) and relapse-free survival (RFS) rates were both 63%. The 3-year OS rates were similar for pts who underwent ASCT and those who did not (75% vs. 63%; P=0.95). The 3-year OS rates for pts with an MRD level of 0.01%>0.1% (n=10) and those >0.1% (n=21) were 72% and 60%, respectively.
Conclusion
Blinatumomab is well-tolerated and highly effective in eradicating MRD in pts with B-cell ALL who have persistent MRD or who experience MRD relapse.
Keyword(s):
Abstract: EP367
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Persistent or recurrent measurable residual disease (MRD) is associated with high rates of relapse in B-cell acute lymphoblastic leukemia (ALL). We evaluated the CD3-CD19 bispecific T-cell engaging antibody, blinatumomab, in patient (pts) with B-cell ALL in complete remission (CR) who did not achieve MRD negativity with standard therapy or who experienced MRD relapse.
Aims
We evaluated the efficacy and safety of blinatumomab in pts with B-cell ALL and MRD-positive disease.
Methods
This is a single-arm, phase II trial of pts with B-cell ALL in CR who did not achieve MRD negativity or had MRD relapse after at least 3 months of frontline therapy (i.e. CR1) or after at least 1 month of salvage therapy (i.e. CR2 and beyond). Positive MRD was defined as ≥0.01% by flow cytometry in pts with Philadelphia chromosome (Ph)-negative ALL and a BCR-ABL1/ABL1 transcript ratio by PCR of ≥0.01% for pts with Ph-positive ALL. MRD negativity was defined as undetectable MRD by flow and PCR at a sensitivity of 10-4. Blinatumomab was given at standard doses (up to 28 µg/day, if tolerated) in 42-day cycles for up to 5 total consolidation cycles. Pts who did not proceed with ASCT could receive blinatumomab maintenance with one cycle every 3 months for up to 4 maintenance cycles (9 cycles total). A TKI of the treating physician's choice was added to the regimen for pts with Ph-positive ALL.
Results
Between 12/2015 and 2/2021, 31 pts with MRD-positive B-cell ALL in CR were enrolled. The median age was 42 years (range, 22-84 years). Thirteen pts (42%) had Ph-positive ALL; 10 pts received concomitant ponatinib, 2 received dasatinib, and 1 received imatinib. Twenty-three pts (74%) were in CR1, and 8 (26%) were in CR2 and beyond (5 in CR2 and 3 in CR3). Nineteen pts (61%) had persistent MRD and 12 (39%) had MRD relapse. Two pts had undergone prior ASCT.
Pts received a median of 3 cycles of blinatumomab consolidation (range, 1-5 cycles). Overall, 23 pts (74%) achieved MRD negativity at any time. Fifteen of 18 pts (83%) with Ph-negative ALL achieved MRD negativity, and 8 of 13 pts (62%) with Ph-positive ALL achieved MRD negativity. Three additional pts with Ph-positive ALL achieved a major molecular response as best response. Among the 23 MRD responders, 21 (91%) responded after 1 cycle; 1 after 2 cycles, and 1 after 4 cycles. MRD response occurred in 65% of pts in CR1 and 100% in CR2+. Eight pts (35% of MRD responders) proceeded to ASCT (5 in CR1 and 3 in CR2+) with median time to ASCT of 3 months (range, 2-6 months).
Blinatumomab-related adverse events were as expected, with adverse events of any grade observed in 12 pts (39%). All resolved with supportive management. One pt discontinued blinatumomab due to adverse event (grade 3 altered mental status). There were no grade 4 or 5 adverse events.
With a median follow-up of 25 months (range, 5-60 months), 7 pts have relapsed (30% of MRD responders). One relapse was in a pt who underwent ASCT and 6 were in pts who did not undergo ASCT (3 in CR1, 2 in CR2, and 1 in CR3). Four relapses were hematologic only, 1 was hematologic plus CNS, 1 was extramedullary only, and 1 was MRD only. The 3-year overall survival (OS) and relapse-free survival (RFS) rates were both 63%. The 3-year OS rates were similar for pts who underwent ASCT and those who did not (75% vs. 63%; P=0.95). The 3-year OS rates for pts with an MRD level of 0.01%>0.1% (n=10) and those >0.1% (n=21) were 72% and 60%, respectively.
Conclusion
Blinatumomab is well-tolerated and highly effective in eradicating MRD in pts with B-cell ALL who have persistent MRD or who experience MRD relapse.
Keyword(s):