Search Results (5)

Background: Limited real-world data (RWD) may provide important information regarding diagnostic and treatment patterns in patients (pts) with AL Amyloidosis. The aim was to analyze the characteristics, treatment approach and clinical outcome of patients in the real-world settings. Materials and Methods: RWD of 60 pts diagnosed with AL amyloidosis were analyzed. Advanced cardiac involvement, Mayo Clinical Stage (CS) IIIa and IIIb, and Revised-Mayo CS III and IV, has been found in 26.7%, and 16.7%, or 33.3% and 16.7%, respectively. Bortezomib (Bz)-based regimens were applied in 36 pts (60%), and alkylating-based regimens in 24 pts (40%). In 8 pts (13.3%) treated initially with CyBorD induction, high-dose therapy with Melphalan and autologous stem cell transplantation (HDT + ASCT) was applied as the first line of treatment. Results: The overall response rate (ORR, ≥partial response) was achieved in 40 pts (70%). Patients treated with Bz-based induction followed by HDT + ASCT achieved significantly better hematologic (p = 0.001), cardiac (p = 0.004) and renal response rates (p = 0.002) in comparison to CyBorD or Alk-based regimens alone. There was no difference in PFS between those groups (p = 0.733), but patients treated with CyBorD + HDT + ASCT had significantly durable OS (p = 0.039). Univariate analysis pointed out the predictive influence of cardiac involvement (Mayo CS and Revised Mayo CS), ASCT eligibility, and hematologic, cardiac, renal and composite response rates. Conclusions: Advanced cardiac involvement and cardiac and hematologic response still retain adverse prognostic impact on the clinical outcome. Bz-based combinations significantly improved the survival of patients with AL amyloidosis, regardless of HDT + ASCT treatment. Full article

Background: A total of 50% of patients with AL amyloidosis have t(11;14) translocation, allowing us to use the selective oral BCL-2 inhibitor venetoclax in their treatment. Case presentation: Our patient was admitted to the gastroenterology department due to weight loss and abdominal pain. An abdominal CT scan revealed some enlarged lymph nodes; therefore, he was referred to the hematology department. A bone marrow biopsy showed massive amorphous amyloid deposition. The sample was positive on Congo red staining and exhibited double refraction under a polarized light microscope. Serum-free light chains and the difference between involved and uninvolved free light chains (dFLCs) were elevated. Using fluorescent in situ hybridization, we detected t(11;14) translocation. Further examinations confirmed the involvement of the liver, colon and heart. Stage II AL amyloidosis was confirmed. Our patient received combined induction therapy with CyBorD and venetoclax due to the presence of the t(11;14) translocation. After six cycles, the patient achieved complete remission. Autologous stem cell transplantation (ASCT) was performed. At 100 days post-ASCT, the patient had complete hematologic remission. Venetoclax maintenance treatment was initiated. The follow-up examinations showed that the patient is in very good partial remission. Conclusions: In the case of our AL amyloidosis patient with t(11;14) translocation, the combined treatment with CyBorD and venetoclax was well tolerated and effective. Full article

Background: Pre-clinical and retrospective data suggest that doxycycline added to treatment regimens has benefit in AL amyloidosis. However, a recent multicenter, open-label, randomized controlled trial in AL amyloidosis patients treated with CyBorD did not demonstrate a progression-free survival (PFS) or cardiac PFS benefit with added doxycycline. Objective: The main objective of this study was to explore the role of doxycycline combined with bortezomib-containing regimens (BCRs) for newly diagnosed AL amyloidosis patients with cardiac involvement and to compare them with a cohort of concurrent patients treated with BCR only. Material and Methods: AL amyloidosis patients, newly diagnosed between January 2012 and March 2022, who were treated with BCR at the Amyloidosis Program of Calgary (APC) were evaluated. Results: Sixty-four concurrent patients were identified. Thirty-nine patients received doxycycline in addition to BCR (BCR-D) for a median of 8 months. The overall response rate was similar among the groups. No significant differences in VGPR/CR, dFLC at 1 month, time to first response, time to best response, or organ responses were noted between the BCR alone and BCR-D groups. Summary and Conclusions: Our retrospective study demonstrated that doxycycline combined with BCR failed to prolong OS, PFS, or cardiac responses compared with BCR alone in patients with cardiac AL amyloidosis. Full article

AL amyloidosis is caused by the excessive production of nonfunctional immunoglobulins, leading to the formation of amyloid fibrils that damage vital organs, especially the heart and kidneys. AL amyloidosis presents with non-specific symptoms such as fatigue, weight loss, numbness, pain, and nephrotic syndrome. Consequently, diagnosis is often delayed, and patients typically present with advanced disease at diagnosis. The Pavia renal staging model stratifies patients based on their likelihood of progressing to dialysis. Treatment with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD) was effective in inducing renal response in the landmark phase III ANDROMEDA trial and reducing early mortality. However, determining the most appropriate treatment regimen for relapsed or refractory cases remains a challenge due to various patient- and disease-related factors. Encouragingly, t(11:14) may be a positive indicator of therapy responses to the anti-BCL2 therapy venetoclax. Moreover, it is increasingly possible—for the first time—to clear AL amyloid fibrils from peripheral organs by leveraging novel anti-fibril immunotherapeutic approaches, although these medications are still under investigation in clinical trials. Given these advancements, this review provides a comprehensive overview of the current strategies for diagnosing, staging, treating, and monitoring AL amyloidosis, emphasizing renal involvement. Full article

Introduction: Cyclophosphamide–bortezomib–dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (MM). It has not been prospectively compared with bortezomib–dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods: In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible MM who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (PFS), response, and stem-cell collection for a first autologous stem-cell transplantation (aHSCT) were compared. Results: Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony–stimulating factor (GCSF). Plerixafor was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9 × 10⁶ cells/kg vs. 7.7 × 10⁶ cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median PFS was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions: Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After aHSCT, no difference in depth of response or PFS was observed. Cyclophosphamide–GCSF seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship. Full article