Contributions
Abstract: S262
Type: Oral Presentation
Session title: Stem cell transplantation - Clinical: Other Complications
Background
Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a serious and life-threatening complication of stem-cell transplant for which there is no approved therapy. Narsoplimab, an inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2) – the effector enzyme of the lectin pathway of complement – is being studied for the treatment of patients with high-risk HSCT-TMA. Submission of a Biologics License Application is underway for approval in the U.S., and a Marketing Authorization Application is being prepared for Europe.
Aims
The aim of this study was to evaluate narsoplimab safety and efficacy in the treatment of HSCT-TMA.
Methods
This is a single-arm pivotal trial in adult HSCT-TMA patients. A high-risk population was targeted with an inclusion criterion that enrolled patients who had not responded to immunosuppression modification. Additional inclusion criteria included thrombocytopenia, evidence of microangiopathic hemolytic anemia (elevated lactate dehydrogenase [LDH], decreased haptoglobin and presence of schistocytes), and increased creatinine. Patients received narsoplimab intravenously once weekly for 4 or 8 weeks with a 6-week follow-up period. The FDA-agreed primary endpoint was a novel response-based composite measure requiring improvement both in laboratory TMA markers (platelet count and LDH) and in clinical status (i.e., organ function [renal, pulmonary, gastrointestinal, or neurological] or transfusion burden). Secondary endpoints were survival and changes in laboratory TMA markers. Two populations (enrolled patients who received any treatment and patients who received the protocol-specified treatment of at least 4 weeks) were analyzed.
Results
28 patients were enrolled and treated (mean age was 48 years; 71% were male; 96% had a malignant underlying disease). This patient population had a high expected death rate. During the period just prior to developing HSCT-TMA and throughout the study, 93% of trial patients had multiple risk factors including graft-versus-host disease (GVHD) (64%), infection (79%), non-infectious pulmonary complications (18%), and neurological signs (36%). 23 patients received at least 4 weeks of treatment. Statistically (p < 0.01) and clinically significant improvements from baseline were observed in platelet count, LDH, and haptoglobin. Table 1 provides the response rate and 100-day survival from the date of TMA diagnosis for all patients and those who received at least the protocol-specified 4 weeks of treatment.
Table 1. Efficacy Measures
Population | Response Rate n/N (%) |
All patients (N = 28) | 15/28 (54%) |
≥ 4 weeks of treatment (N = 23) | 15/23 (65%) |
Population | 100 Day Survival n/N (%) |
All patients (N = 28) | 19/28 (68%) |
4 weeks of treatment (N = 23) | 19/23 (83%) |
Responders only (N = 15) | 14/15 (93%) |
The most common adverse events were nausea, vomiting, diarrhea, hypokalemia, neutropenia and fever. Six deaths occurred, collectively, from sepsis, AML progression, and GVHD. Narsoplimab was very well tolerated, with no reported infusion side effects.
Conclusion
In this trial, most narsoplimab-treated patients achieved a complete response with a significant improvement in laboratory markers and in clinical status. No safety signal was observed.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Stem cell transplant, Treatment
Abstract: S262
Type: Oral Presentation
Session title: Stem cell transplantation - Clinical: Other Complications
Background
Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a serious and life-threatening complication of stem-cell transplant for which there is no approved therapy. Narsoplimab, an inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2) – the effector enzyme of the lectin pathway of complement – is being studied for the treatment of patients with high-risk HSCT-TMA. Submission of a Biologics License Application is underway for approval in the U.S., and a Marketing Authorization Application is being prepared for Europe.
Aims
The aim of this study was to evaluate narsoplimab safety and efficacy in the treatment of HSCT-TMA.
Methods
This is a single-arm pivotal trial in adult HSCT-TMA patients. A high-risk population was targeted with an inclusion criterion that enrolled patients who had not responded to immunosuppression modification. Additional inclusion criteria included thrombocytopenia, evidence of microangiopathic hemolytic anemia (elevated lactate dehydrogenase [LDH], decreased haptoglobin and presence of schistocytes), and increased creatinine. Patients received narsoplimab intravenously once weekly for 4 or 8 weeks with a 6-week follow-up period. The FDA-agreed primary endpoint was a novel response-based composite measure requiring improvement both in laboratory TMA markers (platelet count and LDH) and in clinical status (i.e., organ function [renal, pulmonary, gastrointestinal, or neurological] or transfusion burden). Secondary endpoints were survival and changes in laboratory TMA markers. Two populations (enrolled patients who received any treatment and patients who received the protocol-specified treatment of at least 4 weeks) were analyzed.
Results
28 patients were enrolled and treated (mean age was 48 years; 71% were male; 96% had a malignant underlying disease). This patient population had a high expected death rate. During the period just prior to developing HSCT-TMA and throughout the study, 93% of trial patients had multiple risk factors including graft-versus-host disease (GVHD) (64%), infection (79%), non-infectious pulmonary complications (18%), and neurological signs (36%). 23 patients received at least 4 weeks of treatment. Statistically (p < 0.01) and clinically significant improvements from baseline were observed in platelet count, LDH, and haptoglobin. Table 1 provides the response rate and 100-day survival from the date of TMA diagnosis for all patients and those who received at least the protocol-specified 4 weeks of treatment.
Table 1. Efficacy Measures
Population | Response Rate n/N (%) |
All patients (N = 28) | 15/28 (54%) |
≥ 4 weeks of treatment (N = 23) | 15/23 (65%) |
Population | 100 Day Survival n/N (%) |
All patients (N = 28) | 19/28 (68%) |
4 weeks of treatment (N = 23) | 19/23 (83%) |
Responders only (N = 15) | 14/15 (93%) |
The most common adverse events were nausea, vomiting, diarrhea, hypokalemia, neutropenia and fever. Six deaths occurred, collectively, from sepsis, AML progression, and GVHD. Narsoplimab was very well tolerated, with no reported infusion side effects.
Conclusion
In this trial, most narsoplimab-treated patients achieved a complete response with a significant improvement in laboratory markers and in clinical status. No safety signal was observed.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Stem cell transplant, Treatment