ASH 2025 | Risk-adapted autologous transplant in AL amyloidosis: biomarkers and evolving strategies

The treatment paradigm for patients with AL amyloidosis is really changing. And the Andromeda study, which defined our standard upfront therapy for almost all patients with newly diagnosed AL amyloidosis, which includes the monoclonal antibody daratumumab that was given in combination with bortezomib, cyclophosphamide, and dexamethasone, is really the standard of care for almost all patients. And patients included in that Andromeda study were patients with cardiac stage 1 to 3A, which is really defined by an elevated troponin or an elevated NT-proBNP, whereas an NT-proBNP greater than 8,500 was cardiac stage 3B, which were excluded from that trial, but we’re learning how to treat them either with single agent daratumumab or the combination that was pioneered in the Andromeda study, but just at modified doses. In terms of patients who are transplant candidates, because the treatment with DARA-VCd, as given in the Andromeda study, has been so successful, meaning that 60% of patients who are treated with upfront DARA-VCd achieve a complete hematologic response. The role of stem cell transplant is currently being questioned. And there is a currently ongoing SWOG study, S2213, that is a national study to look at patients treated with initial three cycles of DARA-VCd and then randomizing those patients to either stem cell transplant or ongoing DARA-VCd because the CR rate of 60% with the DARA-VCd really mimics what we see with stem cell transplant plus consolidation. And the patients who are eligible for that study also have to have cardiac biomarkers that puts them in Mayo clinical stage 1 through 3A. And in terms of kidney dysfunction, I think that the majority of patients in clinical trials will require a creatinine clearance of over 30 mLs per minute in order to be considered for clinical trials or a stem cell transplant. We know that we can do stem cell transplants in patients who are dialysis dependent or have lower GFRs, but their risk of developing end-stage kidney disease and the need for hemodialysis is high. However, if we can get those patients into a complete hematologic response, these patients can be candidates for kidney transplantation. So in general, we can treat almost all patients with DARA-VCd up front and stem cell transplant, the utility of it is being questioned at this time because now in the year 2025 we are now developing actually more effective and safer treatments for this condition, namely BCMA-directed therapies like CAR T cells and bispecific antibodies, which have really dramatically changed the therapeutic landscape for patients with plasma cell disorders in general.

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