Contributions
Abstract: EP1036
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Light chain (AL) amyloidosis is a plasma cell disorder where amyloid deposition occurs in various tissues and organs. Heart is affected in most patients and cardiac dysfunction is the leading cause of death. Cardiobiomarker-based staging identifies patients with extremely poor outcomes. These patients with stage 3B disease have a dismal prognosis of just a few months which despite recent advances has not been improved, mainly due to delays in hematologic responses and treatment-related toxicities. Daratumumab (DARA), a human IgG1κ monoclonal antibody which targets CD38, has shown rapid, deep, and high rates of response in patients with AL amyloidosis, and with a favorable safety profile.
Aims
The present analysis aims to evaluate the safety profile of DARA monotherapy in this high-risk population.
Methods
EMN22 is an open-label, multicenter, Phase 2 study aiming to enroll approximately 40 pts from 4 countries (Greece, the Netherlands, Italy, and France) with newly diagnosed stage 3B AL amyloidosis (i.e., with both a high sensitivity Troponin T (hsTnT) >54 pg/ml and NTproBNP ≥8500 pg/ml) who will receive primary therapy with DARA monotherapy. Pts initially received intravenous DARA, but from 2/2020 receive subcutaneous DARA at a fixed dose of 1800 mg, weekly for Cycles 1–2, every 2 weeks for Cycles 3–6, and every 4 weeks thereafter. Treatment continues until disease progression according to Major Organ Deterioration Progression-Free Survival (MOD-PFS) criteria, initiation of subsequent therapy, or a maximum of 2 years. Pts who do not achieve at least a hematologic VGPR, or hematologic PR with cardiac or renal response, may receive at Investigator’s discretion additional treatment with Bortezomib (weekly for a maximum of 6 months) and low dose dexamethasone from Cycle 4. The current analysis includes pts who received the first dose of treatment at least 6 months prior to the cut-off date (31/01/2021).
Results
Overall, 7 pts were included. Median age was 65 years, and the majority were male (6 pts). Median baseline NT-proBNP and hsTnT levels were 33,442 and 166 pg/mL, respectively. ECOG Performance Status was 1 for 4 pts, 2 for 2 pts and 3 for 1 pt. Pts have received a median of 13 cycles, and until the cut-off date 4 pts are still on treatment; 3 pts died due to complications of the disease; no patient died due to treatment-related cardiac complications. In total, 6 pts had ≥1 adverse event (AE) grade 3 or 4, and 5 pts experienced ≥1 serious adverse event (SAE). No IRRs were reported. Most common grade 3/4 AEs were dyspnea (3 pts), atrial fibrillation (2 pts), and peripheral edema (2 pts). There were 10 SAEs reported: congestive heart failure (n=2, one of them fatal), dyspnea (n=2), atrial fibrillation, intracranial hemorrhage, muscle hemorrhage, sepsis (fatal), septic shock, and sudden death (1 pt each). Overall, 4 pts achieved a hematologic response (median time to first response <1 month), with 1 pt reaching PR, 2 pts VGPR, and 1 pt CR (also MRD negative). From the deceased pts, one died while in unconfirmed hematologic response while 2 pts had already discontinued treatment due to hematologic progression and major organ deterioration. The 6-month OS rate was 57.1%.
Conclusion
This early analysis shows that DARA monotherapy is safe with no treatment-related safety events or any signal of cardiac toxicity in patients with stage 3B disease. The enrollment in the study continues and more data will be available on safety and efficacy with the inclusion of additional patients in the updated analysis.
Keyword(s): AL amyloidosis, High risk
Abstract: EP1036
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Light chain (AL) amyloidosis is a plasma cell disorder where amyloid deposition occurs in various tissues and organs. Heart is affected in most patients and cardiac dysfunction is the leading cause of death. Cardiobiomarker-based staging identifies patients with extremely poor outcomes. These patients with stage 3B disease have a dismal prognosis of just a few months which despite recent advances has not been improved, mainly due to delays in hematologic responses and treatment-related toxicities. Daratumumab (DARA), a human IgG1κ monoclonal antibody which targets CD38, has shown rapid, deep, and high rates of response in patients with AL amyloidosis, and with a favorable safety profile.
Aims
The present analysis aims to evaluate the safety profile of DARA monotherapy in this high-risk population.
Methods
EMN22 is an open-label, multicenter, Phase 2 study aiming to enroll approximately 40 pts from 4 countries (Greece, the Netherlands, Italy, and France) with newly diagnosed stage 3B AL amyloidosis (i.e., with both a high sensitivity Troponin T (hsTnT) >54 pg/ml and NTproBNP ≥8500 pg/ml) who will receive primary therapy with DARA monotherapy. Pts initially received intravenous DARA, but from 2/2020 receive subcutaneous DARA at a fixed dose of 1800 mg, weekly for Cycles 1–2, every 2 weeks for Cycles 3–6, and every 4 weeks thereafter. Treatment continues until disease progression according to Major Organ Deterioration Progression-Free Survival (MOD-PFS) criteria, initiation of subsequent therapy, or a maximum of 2 years. Pts who do not achieve at least a hematologic VGPR, or hematologic PR with cardiac or renal response, may receive at Investigator’s discretion additional treatment with Bortezomib (weekly for a maximum of 6 months) and low dose dexamethasone from Cycle 4. The current analysis includes pts who received the first dose of treatment at least 6 months prior to the cut-off date (31/01/2021).
Results
Overall, 7 pts were included. Median age was 65 years, and the majority were male (6 pts). Median baseline NT-proBNP and hsTnT levels were 33,442 and 166 pg/mL, respectively. ECOG Performance Status was 1 for 4 pts, 2 for 2 pts and 3 for 1 pt. Pts have received a median of 13 cycles, and until the cut-off date 4 pts are still on treatment; 3 pts died due to complications of the disease; no patient died due to treatment-related cardiac complications. In total, 6 pts had ≥1 adverse event (AE) grade 3 or 4, and 5 pts experienced ≥1 serious adverse event (SAE). No IRRs were reported. Most common grade 3/4 AEs were dyspnea (3 pts), atrial fibrillation (2 pts), and peripheral edema (2 pts). There were 10 SAEs reported: congestive heart failure (n=2, one of them fatal), dyspnea (n=2), atrial fibrillation, intracranial hemorrhage, muscle hemorrhage, sepsis (fatal), septic shock, and sudden death (1 pt each). Overall, 4 pts achieved a hematologic response (median time to first response <1 month), with 1 pt reaching PR, 2 pts VGPR, and 1 pt CR (also MRD negative). From the deceased pts, one died while in unconfirmed hematologic response while 2 pts had already discontinued treatment due to hematologic progression and major organ deterioration. The 6-month OS rate was 57.1%.
Conclusion
This early analysis shows that DARA monotherapy is safe with no treatment-related safety events or any signal of cardiac toxicity in patients with stage 3B disease. The enrollment in the study continues and more data will be available on safety and efficacy with the inclusion of additional patients in the updated analysis.
Keyword(s): AL amyloidosis, High risk