Treatment With Bortezomib-based Therapy, Followed by Autologous Stem Cell Transplantation, Improves Outcomes in Light Chain Amyloidosis: A Retrospective Study.
We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis. PATIENTS AND METHODS: Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT). A greater number of patients had involvement of ≥ 3 organs and cardiac involvement in the Bor-ASCT group, suggesting a greater risk at baseline in the Bor-ASCT group. RESULTS: At 3, 6, and 12 months after ASCT, the hematologic response was better in the Bor-ASCT group, with a statistically significance difference at 6 months (partial response or better in 82% vs. 20%; P = .002) and 12 months (partial response or better in 76% vs. 33%; P = .02). Organ responses (66% vs. 21%; P
ConclusionOutpatient ASCT is a safe and feasible treatment strategy with low transplant-related mortality. Overall resource utilization is significantly lower than inpatient ASCT: however, this requires a multidisciplinary approach with close follow-up.
Publication date: October 2019Source: Clinical Lymphoma Myeloma and Leukemia, Volume 19, Issue 10, SupplementAuthor(s): Abdullah S. Al Saleh, M Hasib Sidiqi, Surbhi Sidana, Eli Muchtar, Angela Dispenzieri, David Dingli, Martha Lacy, Rahma Warsame, Wilson Gonsalves, Taxiarchis Kourelis, William Hogan, Suzanne Hayman, Robert Wolf, Prashant Kapoor, Francis Buadi, Shaji Kumar, Morie A. Gertz
ConclusionOutpatient ASCT is a safe and feasible treatment strategy with low TRM. Overall resource utilization are significantly lower than inpatient auto-transplantation: however, this requires a multidisciplinary approach with close follow up
Beginning with a comprehensive, multidisciplinary evaluation leading to treatment of patients with high dose melphalan (HDM) and autologous stem cell transplantation (SCT) requires excellent coordination of care, clear communication and collaboration within the team. The use of clinical pathways (CPs) provide direction in delivering precise and intentional care for a specific patient population. CPs were first used in a hospital setting in the 1980's in response to changes in healthcare, shifting the focus from volume to quality.
Light chain amyloidosis (AL) is characterized by the presence of monoclonal plasma cell and deposition of immunoglobulin light chain derived amyloid deposits in various organs. The outcome of patients with primary systemic AL amyloidosis is generally poor especially with organ involvement, such as cardiac and renal involvement. Treatment with chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) can result in improve survival outcome in these patients.
The standard of care for AL amyloidosis, in patients who are not candidates for a stem cell transplant, is based on Bortezomib-based chemotherapy. Unfortunately, patients harboring the t(11;14), who represent up to 50% of AL amyloidosis cases, have a poor response to Bortezomib. Daratumumab (Dara), a monoclonal antibody targeting CD38 approved for the treatment of patients for multiple myeloma, has been shown to be highly active in heavily pretreated patients with AL amyloidosis (Kaufman et al, Blood 2017).
Autologous stem cell transplantation (ASCT) is an effective therapy for eligible patients with immunoglobulin light chain amyloidosis (AL) and is able to induce deep and durable remissions. However, not all patients achieve a deep response after ASCT and the role of consolidation post ASCT in AL amyloidosis is not well defined.
High-dose melphalan prior to AHCT for MM and AL patients is currently given as a fixed dose based on body surface area leading to inter-patient differences in area under the curve (AUC). Increased exposure (higher AUC) leads to increased toxicity, but longer survival (Shaw et al., BBMT 2012). To optimize therapy, we evaluated the feasibility of PK-directed dosing of PGF-MEL (Acrotech Biopharma), a more stable and possibly less toxic intravenous formulation of melphalan.
Autologous Stem Cell Transplant (ASCT) with High-Dose Melphalan conditioning has been a unchallenged standard for intensive consolidation therapy in younger fitter Multiple Myeloma (MM) since late 1990,&was ratified as increasing PFS&OS, through RCT by various collaborative groups, as well as meta-analysis.However induction regimens have evolved from anthracycline-based infusions (e.g. [C]VAD&DTPACE]), through thal-&now len- alidomide-based IMid regimens (CTD/DTPACE/CRD), alongside advent of proteasome-inhibitors (esp.
Immunoglobulin light chain amyloidosis (AL) is a plasma cell (PC) dyscrasia characterized by a neoplastic malignant PC population producing highly toxic light chains. Despite overlapping features with multiple myeloma (MM), therapeutic options are limited as a result of disease-specific treatment toxicities. Given delays in diagnosis, patients often present with advanced disease, making them poor candidates for autologous stem-cell transplantation.