None listed
Conditions
Brief summary
Brief Summary: This study investigates the relationship between the immune microenvironment and Minimal Residual Disease (MRD) response in patients with amyloid light chain (AL) Amyloidosis treated with standard-of-care Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone (D-VCD). It aims to improve MRD monitoring through novel flow cytometry and mass spectrometry techniques in peripheral blood, and to correlate these with bone marrow MRD assessed via EuroFlow. Aim: Unmet Need While most patients respond well to D-VCD, a subset experiences suboptimal outcomes. There is a need to identify these patients early and refine MRD detection methods to guide treatment decisions more effectively. Who is it for: Adults diagnosed with AL amyloidosis who are receiving first-line treatment with D-VCD, are eligible for MRD assessment and sample collection, and consented onto the National Blood Cancer Registry (NBCR). Study Design: Prospective, observational correlative science study. Peripheral blood samples will be collected at baseline and at the start of the 6 treatment cycles, with bone marrow and blood collected post-induction and prior to maintenance therapy. MRD will be assessed using EuroFlow in bone marrow and novel flow cytometry and mass spectrometry in peripheral blood. It is hoped this study will: Identify immunological markers associated with MRD clearance. Improve MRD detection sensitivity and concordance between bone marrow and peripheral blood. Enable earlier identification of patients at risk of poor outcomes. Support MRD-guided treatment strategies in AL amyloidosis.
Interventions
Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone (D-VCD) is the standard of care (SOC) for front-line treatment of amyloid light chain (AL) Amyloidosis patients. The treatment regime of D-VCD is 6 cycles with each cycle lasting for 28 days followed by monthly maintenance with Daratumumab for 6 months. Whilst outcomes for most patients are excellent, there is a need to identify patients who will have suboptimal outcomes and may require additional therapy.
This correlative study inves
Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone (D-VCD) is the standard of care (SOC) for front-line treatment of amyloid light chain (AL) Amyloidosis patients. The treatment regime of D-VCD is 6 cycles with each cycle lasting for 28 days followed by monthly maintenance with Daratumumab for 6 months. Whilst outcomes for most patients are excellent, there is a need to identify patients who will have suboptimal outcomes and may require additional therapy. This correlative study investigates the immune microenvironment and its association with Minimal Residual Disease (MRD) clearance in patients with AL amyloidosis receiving front-line SOC therapy with D-VCD. Participants will receive D-VCD regardless of participation as it is SOC for front-line treatment of amyloid light chain (AL) Amyloidosis patients. The study aims to explore the relationship between the immune microenvironment and MRD clearance, and evaluate the concordance of MRD detection between bone marrow (BM) and peripheral blood (PB) using novel flow cytometry and mass spectrometry techniques. Study procedures include: 1) Peripheral blood (PB) sampling prior to treatment initiation or within the first cycle, and at the beginning of cycles 2 through 6. 2) Bone marrow biopsy and PB collection at the completion of D-VCD therapy and prior to or within one month of commencing maintenance single-agent Daratumumab. MRD assessment will be performed using EuroFlow in BM and novel flow cytometry and mass spectrometry in PB. EuroFlow MRD results will be reported back to the referring clinical site. Clinical data will be captured via the Australia and New Zealand Myeloma and Related Diseases Registry (MRDR). The overall duration of participation for each participant is 1 year. This study seeks to improve MRD monitoring and identify patients with suboptimal responses who may benefit from additional therapeutic strategies.
Sponsors
Australasian Leukaemia and Lymphoma Group
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with AL Amyloidosis as per the Pharmaceutical Benefits Scheme (PBS) guidelines receiving D-VCD as SOC treatment. Note: patients who cease this therapy early or undergo dose modifications due to toxicity or other will remain eligible. 2. The Myeloma and Related Diseases Registry (MRDR) is an opt out consent process and patients must not have opted out of MRDR to be included in this study.
Exclusion criteria
N/A
Outcome results
None listed