Contributions
Abstract: S856
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 17:00 - 17:15
Location: Victoria Hall
Background
Moxetumomab pasudotox, a first-in-class recombinant immunotoxin targeting CD22, is composed of an immunoglobulin light chain variable domain and a heavy chain variable domain genetically fused to a truncated form of Pseudomonas exotoxin PE38.
Aims
This pivotal multicenter, single-arm study evaluated the rate of durable complete response with moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia (HCL).
Methods
Eligible patients had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 of 28-d cycles, up to 6 cycles. Disease response and immunohistochemistry (IHC) minimal residual disease (MRD) status were determined by blinded independent central review. The primary end point was durable complete response (CR), defined as CR with hematologic remission (HR; blood count normalization) for >180 days.
Results
Eighty patients (63 male; median age 60 years) received moxetumomab pasudotox. The median number of prior systemic therapies was 3 (2–11); 39 patients (49%) had >3 prior lines of therapy and 60 (75%) had prior rituximab. At 16.7 months median follow-up, objective response (OR) rate was 75% (60/80), HR rate was 80% (64/80), CR rate was 41% (33/80), and durable CR rate was 30% (24/80). Of 33 patients achieving CR, 27 (82%) had IHC MRD negative status. Median time to HR was 1 month. Median duration of OR and median PFS were not reached. Most frequent treatment-related adverse events (AEs) were nausea (28%), peripheral edema (26%), headache (21%), and pyrexia (20%); 8% had infections and 3% had neutropenia deemed treatment related. Three deaths occurred; none were treatment related. Treatment-related AEs leading to discontinuation were hemolytic uremic syndrome (HUS; n=4 [5%]), capillary leak syndrome (CLS; n=2 [3%]), and increased blood creatinine (n=2 [3%]). Seven patients (9%) had CLS (grade 2: n=5; grade 4: n=2), 7 (9%) had HUS (grade 2: n=2; grade 3: n=3; grade 4: n=2), and 4 (5%) had both. Both CLS and HUS were manageable and reversible with dose interruption and discontinuation in severe cases (no plasma exchange in HUS). Median immunoglobulin levels remained unchanged after treatment. Median CD4 cell counts were stable or improved after the first week of treatment.
Conclusion
Moxetumomab pasudotox achieved a high rate of independently assessed durable CR, with the ability to eradicate MRD in heavily pretreated HCL patients, and showed a favorable safety profile without immuno/myelosuppression.
Session topic: 20. Indolent Non-Hodgkin lymphoma – Clinical
Keyword(s): Hairy cell leukemia, Minimal residual disease (MRD)
Abstract: S856
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 17:00 - 17:15
Location: Victoria Hall
Background
Moxetumomab pasudotox, a first-in-class recombinant immunotoxin targeting CD22, is composed of an immunoglobulin light chain variable domain and a heavy chain variable domain genetically fused to a truncated form of Pseudomonas exotoxin PE38.
Aims
This pivotal multicenter, single-arm study evaluated the rate of durable complete response with moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia (HCL).
Methods
Eligible patients had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 of 28-d cycles, up to 6 cycles. Disease response and immunohistochemistry (IHC) minimal residual disease (MRD) status were determined by blinded independent central review. The primary end point was durable complete response (CR), defined as CR with hematologic remission (HR; blood count normalization) for >180 days.
Results
Eighty patients (63 male; median age 60 years) received moxetumomab pasudotox. The median number of prior systemic therapies was 3 (2–11); 39 patients (49%) had >3 prior lines of therapy and 60 (75%) had prior rituximab. At 16.7 months median follow-up, objective response (OR) rate was 75% (60/80), HR rate was 80% (64/80), CR rate was 41% (33/80), and durable CR rate was 30% (24/80). Of 33 patients achieving CR, 27 (82%) had IHC MRD negative status. Median time to HR was 1 month. Median duration of OR and median PFS were not reached. Most frequent treatment-related adverse events (AEs) were nausea (28%), peripheral edema (26%), headache (21%), and pyrexia (20%); 8% had infections and 3% had neutropenia deemed treatment related. Three deaths occurred; none were treatment related. Treatment-related AEs leading to discontinuation were hemolytic uremic syndrome (HUS; n=4 [5%]), capillary leak syndrome (CLS; n=2 [3%]), and increased blood creatinine (n=2 [3%]). Seven patients (9%) had CLS (grade 2: n=5; grade 4: n=2), 7 (9%) had HUS (grade 2: n=2; grade 3: n=3; grade 4: n=2), and 4 (5%) had both. Both CLS and HUS were manageable and reversible with dose interruption and discontinuation in severe cases (no plasma exchange in HUS). Median immunoglobulin levels remained unchanged after treatment. Median CD4 cell counts were stable or improved after the first week of treatment.
Conclusion
Moxetumomab pasudotox achieved a high rate of independently assessed durable CR, with the ability to eradicate MRD in heavily pretreated HCL patients, and showed a favorable safety profile without immuno/myelosuppression.
Session topic: 20. Indolent Non-Hodgkin lymphoma – Clinical
Keyword(s): Hairy cell leukemia, Minimal residual disease (MRD)