Contributions
Abstract: S104
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:30 - 12:45
Location: Hall A
Background
Light chain (AL) amyloidosis is a rare and often fatal disease caused by the accumulation of misfolded light chain (LC) aggregates that can lead to progressive failure of critical organs, causing significant morbidity and mortality. Patients’ survival depends upon rapid suppression of the misfolded LC and stabilization or recovery of organ function. Current therapies limit LC production; however, ~75% of patients have persistent organ dysfunction. NEOD001 is a novel investigational monoclonal antibody that targets misfolded LC and may neutralize circulating LC aggregates and clear insoluble deposits.
Aims
To assess the association between responses and time, depth, number or type of previous plasma cell–directed (PCD) treatments and organ response.
Methods
Inclusion criteria for this trial were: completed ≥1 PCD treatment before enrollment, attained partial hematologic response (HR) or better to any previous therapy, and have persistent organ dysfunction. NEOD001 was administered intravenously every 28 days. During the dose-escalation phase, 27 patients received NEOD001 at 0.5, 1, 2, 4, 8, 16, or 24 mg/kg in a 3+3 study design. In the expansion phase, 42 additional patients with renal, cardiac, or nerve involvement were enrolled and treated (24 mg/kg). We assessed cardiac and renal best responses based on consensus criteria. Peripheral nervous system (PN) responses were assessed at month 10 (after 9 infusions) using the Neuropathy Impairment Score–Lower Limbs (NIS-LL). We explored the potential impact on organ response of the number and type of organs affected and the number of, type of, and time since previous therapies at baseline.
Results
In the overall population (N=69), the median age was 61 years (61% male). Median (range) time since diagnosis was 2.9 (0.4-16.0) years, and 45% of patients underwent ≥3 previous PCD regimens. Median time to first best response was 1.8 (cardiac), 3.7 (renal), and 1.0 (PN) months. Best response rate indicating organ response was observed in 53% of cardiac-evaluable patients (n=19/36) and 64% of renal-evaluable patients (n=23/36). PN responses were observed in 82% (n=9/11) of PN-evaluable patients. Time from patients’ best HR to previous PCD treatment was not related to the attainment of NEOD001 organ response (responder/stable: 35.6/36/6 months [cardiac] and 30.6/32.5 months [renal]; P>0.05). Depth of patients’ best HR also was not related to the attainment of NEOD001 organ response (percentage of patients with organ response in CR/VGPR/PR after PCD: 47.1/66.7/42.9% [cardiac] and 68.8/63.6/62.5% [renal]; P>0.05). Similarly, time or depth of patients’ last HR did not impact the NEOD001 organ response rate (P>0.05). Patients with NEOD001 organ responses were no more likely to have had their last PCD therapy <6 than ≥6 months from their first NEOD001 dose. Patients’ previous PCD treatment type was not related to the attainment of NEOD001 organ response (percentage of patients undergoing: stem cell transplantation, 55.6/61.1% [cardiac/renal]; bortezomib-based therapy, 52.0/68.8%; or other chemotherapy, 50.0/57.1%; P>0.05). Exploratory analyses showed no association between the time to response or percentage of responders and the number of previous PCD treatments.
Conclusion
NEOD001 specifically targets disease-causing, misfolded LC aggregates in AL amyloidosis. Organ responses in patients treated with monthly NEOD001 infusions were achieved rapidly and independently of time since previous chemotherapy, depth of hematologic response, or predominant type of PCD treatment.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Renal, Monoclonal antibody, AL amyloidosis
Abstract: S104
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:30 - 12:45
Location: Hall A
Background
Light chain (AL) amyloidosis is a rare and often fatal disease caused by the accumulation of misfolded light chain (LC) aggregates that can lead to progressive failure of critical organs, causing significant morbidity and mortality. Patients’ survival depends upon rapid suppression of the misfolded LC and stabilization or recovery of organ function. Current therapies limit LC production; however, ~75% of patients have persistent organ dysfunction. NEOD001 is a novel investigational monoclonal antibody that targets misfolded LC and may neutralize circulating LC aggregates and clear insoluble deposits.
Aims
To assess the association between responses and time, depth, number or type of previous plasma cell–directed (PCD) treatments and organ response.
Methods
Inclusion criteria for this trial were: completed ≥1 PCD treatment before enrollment, attained partial hematologic response (HR) or better to any previous therapy, and have persistent organ dysfunction. NEOD001 was administered intravenously every 28 days. During the dose-escalation phase, 27 patients received NEOD001 at 0.5, 1, 2, 4, 8, 16, or 24 mg/kg in a 3+3 study design. In the expansion phase, 42 additional patients with renal, cardiac, or nerve involvement were enrolled and treated (24 mg/kg). We assessed cardiac and renal best responses based on consensus criteria. Peripheral nervous system (PN) responses were assessed at month 10 (after 9 infusions) using the Neuropathy Impairment Score–Lower Limbs (NIS-LL). We explored the potential impact on organ response of the number and type of organs affected and the number of, type of, and time since previous therapies at baseline.
Results
In the overall population (N=69), the median age was 61 years (61% male). Median (range) time since diagnosis was 2.9 (0.4-16.0) years, and 45% of patients underwent ≥3 previous PCD regimens. Median time to first best response was 1.8 (cardiac), 3.7 (renal), and 1.0 (PN) months. Best response rate indicating organ response was observed in 53% of cardiac-evaluable patients (n=19/36) and 64% of renal-evaluable patients (n=23/36). PN responses were observed in 82% (n=9/11) of PN-evaluable patients. Time from patients’ best HR to previous PCD treatment was not related to the attainment of NEOD001 organ response (responder/stable: 35.6/36/6 months [cardiac] and 30.6/32.5 months [renal]; P>0.05). Depth of patients’ best HR also was not related to the attainment of NEOD001 organ response (percentage of patients with organ response in CR/VGPR/PR after PCD: 47.1/66.7/42.9% [cardiac] and 68.8/63.6/62.5% [renal]; P>0.05). Similarly, time or depth of patients’ last HR did not impact the NEOD001 organ response rate (P>0.05). Patients with NEOD001 organ responses were no more likely to have had their last PCD therapy <6 than ≥6 months from their first NEOD001 dose. Patients’ previous PCD treatment type was not related to the attainment of NEOD001 organ response (percentage of patients undergoing: stem cell transplantation, 55.6/61.1% [cardiac/renal]; bortezomib-based therapy, 52.0/68.8%; or other chemotherapy, 50.0/57.1%; P>0.05). Exploratory analyses showed no association between the time to response or percentage of responders and the number of previous PCD treatments.
Conclusion
NEOD001 specifically targets disease-causing, misfolded LC aggregates in AL amyloidosis. Organ responses in patients treated with monthly NEOD001 infusions were achieved rapidly and independently of time since previous chemotherapy, depth of hematologic response, or predominant type of PCD treatment.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Renal, Monoclonal antibody, AL amyloidosis