Reduced Cardiac Risk Factors in AL Amyloidosis with D-VCd | Vaishali Sanchorawala, MD

Hello, I'm Vaishali Sencharawala from Boston University and Boston Medical Center. I'm here at the 67th annual American Society of Hematology meeting in Orlando. There have been several research clinical trials that have been presented at this meeting for systemic AL immunoglobulin light chain amyloidosis. I presented results of phase two Aquarius study at this meeting. AL amyloidosis is a rare disease. It is a plasma cell dyscrasia and there is amyloid fibroide deposition in vital organs which is derived from the immunoglobulin light chains produced by the clonal plasma cells. Hematologic involvement remains the strongest predictor of poor survival in patients with AL amyloidosis. In phase three Andromeda clinical trial, Dara-Tumumab, Bortizumib, Cyclophosphamide, Dexamethasone or Dara-VCD led to significantly higher hematologic responses, organ responses, major organ deterioration progression free survival and overall survival compared to VCD alone and this led to approval of Dara-VCD in the treatment of newly diagnosed patients with AL amyloidosis. In phase two Aquarius study, we looked at different regimens of Dara-VCD, different treatment schedules of Dara-VCD to evaluate cardiac safety, cardiac events and also look at pharmacokinetics in minority patients with AL amyloidosis and cardiac involvement. The Aquarius clinical study, the primary endpoints of this trial were to look at and characterize assess cardiac safety in patients with newly diagnosed AL amyloidosis as well as look at pharmacokinetics in minority patient population. The key eligibility criteria to participate on this study required new diagnosis of AL amyloidosis. In cohort one, patients required to have cardiac involvement and they were randomized to two to one. Arm A of cohort one received the same treatment schedule as Andromeda, which was Dara-Tumumab and VCD starting at the same time called Dara-Immediate VCD. The interventions arm was arm B of cohort one where VCD was introduced after three cycles of Dara-Tumumab during cycle four and this was referred as Dara-Deferred VCD. Cohort two of this Aquarius clinical trial enrolled patients who were minority in race and ethnicity and the purpose of this arm was to evaluate pharmacokinetics in minority patients. Although the results of pharmacokinetics will not be presented at this meeting, 23 patients with cardiac involvement in this arm were included in the analysis. In total, 142 patients with cardiac involvement were enrolled in Aquarius phase two study. The follow up for this study is 12 cycles or 12 months from the first dose of treatment. The first one treatment duration on both groups Dara-Immediate VCD and Dara-Deferred VCD was 10.4 months. There were approximately 80% of patients received at least greater than 10 cycles of treatment on both groups. 10% of patients discontinued the study predominantly due to death. There were nine treatment emergent deaths and two deaths occurred in the Dara-Immediate VCD group within 60 days of treatment initiation. They were attributed as not being related to treatment but related to cardiac amyloidosis. The cardiac emergent, cardiac treatment emergent adverse events were 48.5% in Dara-Immediate VCD group and most of these adverse events occurred between cycles one to three. Cardiac adverse events in contrast was higher at 61.5% in Dara-Deferred VCD group and most frequently occurred during cycles four to cycles six and as a reminder VCD was initiated in this group at cycle four. Cardiac adverse events were low and comparable between the two groups from cycles seven to nine and cycles 10 to 12. Other cardiac adverse events were similar between the two groups and the most common one was cardiac failure. Furthermore, the characterization of these cardiac adverse events were more common and frequent in patients with a higher baseline Mayo stage three disease. An independent adjudication committee adjudicated 20 patients and 30 major cardiac events and again the baseline cardiac risk profile was worse for those who experienced major serious cardiac events in both groups compared to those who did not experience these events. Hematologic complete response was similar between the two treatment groups and it was 59% for Dara-Deferred VCD and 62% for Dara-Immediate VCD group. However, the median time to hematologic complete response was approximately two months for Dara-Immediate VCD and was little longer for Dara-Deferred VCD at 113 days or close to two months. Functional capacity, cardiac signs and symptoms and cardiac biomarkers decreased over time in both treatment groups. In conclusion, Dara-VCD, whether given as immediate VCD or deferred VCD, did show significantly high hematologic efficacy and manageable cardiac safety profile and again really suggesting that this treatment can be delivered safely in patients with cardiac involvement and new diagnosis of ALM loidosis. Thank you. If this video has helped you in any way and you are able to, please consider making a donation to help us continue this important work. Your gift will go three times as far when we reach $500,000 by the end of the year. Every contribution, big or small, makes a difference and we're deeply grateful for your support.