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Systemic light-chain (AL) amyloidosis is a rare and debilitating disease. Advances have been made in new treatments in recent years, yet real-world data on the management of the disease are scarce. EMN23 is a retrospective, observational study of patients who initiated first-line treatment in 2004–2018 in Europe, presenting the demographics, clinical characteristics, treatment patterns, and outcomes, from 4480 patients. Regimens based on bortezomib were the most frequently used as first-line therapy; only 6.2% of the patients received autologous stem cell transplant. Hematologic responses improved post-2010 (67.1% vs 55.6% pre-2010). The median overall survival (OS) was 48.8 (45.2–51.7) months; 51.4 (47.3–57.7) months pre-2010 and 46.7 (41.3–52.2) months post-2010. Early mortality was 13.4% and did not improve (11.4% vs 14.4% pre- and post-2010); furthermore, it remained high in patients with advanced cardiac disease (over 39% for stage IIIb). There was a significant improvement for stage IIIa (14.2 vs 30.7 months, p = 0.0170) but no improvement for stage IIIb patients (5.0 vs 4.5 months). This European real-world study of AL-amyloidosis emphasizes the unmet needs of early diagnosis, and the lack of improvement in survival outcomes of the frail stage IIIb population, despite the introduction of new therapies in recent years. [ABSTRACT FROM AUTHOR]

There is little long-term outcome data on the efficacy of autologous hematopoietic stem cell transplantation (ASCT) in light chain deposition disease (LCDD). We identified 51 LCDD patients in the European Society for Blood and Bone Marrow transplantation registry who had undergone upfront ASCT between 1995 and 2021. The median serum creatinine was 280 μmol/L and 45% required renal replacement therapy (RRT) at time of transplant. The melphalan dose was 100 mg/m2 in 23%, 140 mg/m2 in 55% and 200 mg/m2 in 21%. The rate of very good partial response or better improved from 41% pretransplant to 66% at day +100 post- ASCT. In RRT-independent patients, there was a modest improvement in renal function within the first 3 months; the median estimated glomerular filtration rate increased from 44 to 51 mL/min/1.73 m2. There was no further change between 3 and 12 months post-ASCT. No patient who was RRT-independent at ASCT became RRT dependent by day + 100 post-ASCT. Median follow- up post-ASCT was 84 months (interquartile range [IQR]: 46-122). At 6-years post ASCT, overall survival was 88% (95% confidence interval [CI]: 78-98) and PFS was 44% (95% CI: 28-60). The 2-year cumulative incidence of relapse and non-relapse mortality was 17% (95% CI: 6-27) and 2% (95% CI: 0-6), respectively. The cumulative incidence of renal transplantation at 4 years after ASCT was 27% (95% CI: 13-41) with renal transplantation performed between 6.3 and 52.9 months post-ASCT (median 24.7 months). ASCT represents a feasible option for LCDD patients even if RRT dependent at time of transplant. Outcomes are favorable with low non-relapse mortality and good long-term overall survival.

Objectives: To report healthcare resource utilization (HCRU) and safety outcomes in systemic light chain (AL) amyloidosis from the EMN23 study., Materials and Methods: The retrospective, observational, multinational EMN23 study included 4,480 patients initiating first-line treatment for AL amyloidosis in 2004-2018 and assessed, among other objectives, HCRU and safety outcomes. HCRU included hospitalizations, examinations, and dialysis; safety included serious adverse events (SAEs) and adverse events of special interest (AESIs). Data were descriptively analyzed by select prognostic factors (e.g., cardiac staging by Mayo2004/European) for 2004-2010 and 2011-2018. A cost-of-illness analysis was conducted for the UK and Spain., Results: HCRU/safety and dialysis data were extracted for 674 and 774 patients, respectively. Of patients with assessed cardiac stage (2004-2010: 159; 2011-2018: 387), 67.9% and 61.0% had ≥ 1 hospitalization, 56.0% and 51.4% had ≥ 1 SAE, and 31.4% and 28.9% had ≥ 1 AESI across all cardiac stages in 2004-2010 and 2011-2018, respectively. The per-patient-per-year length of hospitalization increased with disease severity (cardiac stage). Of patients with dialysis data (2004-2010: 176; 2011-2018: 453), 23.9% and 14.8% had ≥ 1 dialysis session across all cardiac stages in 2004-2010 and 2011-2018, respectively. The annual cost-of-illness was estimated at €40,961,066 and €31,904,386 for the UK and Spain, respectively; dialysis accounted for ∼28% (UK) and ∼35% (Spain) of the total AL amyloidosis costs., Conclusions: EMN23 showed that the burden of AL amyloidosis is substantial, highlighting the need for early disease diagnosis and effective treatments targeting the underlying pathology., Competing Interests: Disclosure Arnaud Jaccard, honoraria from Servier, Amgen, Abbvie, and Pfizer; participating in advisory committees for Janssen; research funding from Sanofi and Janssen; Frank Bridoux, lecture fees from Janssen, Astra Zeneca, GSK, and Novartis; consultancy for Janssen, Attralus and Astra Zeneca; Wilfried Roeloffzen, honoraria/advisory board from Janssen, MSD, Amgen, and Sanofi; Monique C. Minnema, honoraria from BMS; consultancy for Janssen-Cilag, GSK, CDR life and Gilead; speaker's bureau for Medscape. Research support from Beigene; Rui Bergantim, honoraria/advisory board from Janssen, BMS, Amgen, Takeda and Pfizer; research funding from BMS and Amgen; Roman Hájek, consultancy/advisory relationship with Janssen, Amgen, Celgene, Abbvie, BMS, Novartis, PharmaMar, and Takeda; honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda; Cristina João, scientific advisory for Takeda, BMS, Janssen, GSK, and Amgen, Abbvie, Pfizer; M. Teresa Cibeira, honoraria for lectures/advisory board for Janssen, Amgen, Akcea, and Sanofi; Giovanni Palladini; participating in advisory boards for Alexion, Argobio, Janssen, and Protego; honoraria from Alexion, Argobio, Janssen, Protego, The Binding Site, Pfizer, Prothena, Sebia, and Siemens; research funding from Gate bioscience and The Binding Site; Stefan Schönland, research support from Janssen, Prothena, and Sanofi; participating in advisory boards for Janssen, Telix, and Prothena; honoraria from Janssen, Takeda, Pfizer, and Prothena; travel and congress participation grants from Janssen, Prothena, Celgene, Binding Site, and Jazz; Paolo Milani, speaker honoraria from Janssen and Pfizer; participating in advisory board for Janssen; Meletios A. Dimopoulos, honoraria from participation in advisory boards from Abbvie, Amgen, Bristol Myers Squibb, Beigene Inc, GSK, Janssen, Karyopharm, Pfizer, Regeneron, Sanofi and Takeda; Ute Hegenbart, travel grants from Janssen, Prothena, and Pfizer; participating in advisory boards for Pfizer, Janssen, and Prothena; honoraria from Janssen, Pfizer, Alnylam, and Akcea; research funding from Janssen and Prothena; Blanca Gros, current employment with Janssen; Aisha Asra, current employment with Janssen; Valeria Magarotto, current employment with Janssen; Giorgos Cheliotis, current employment with Health Data Specialists; Giorgos Psarros, current employment with Health Data Specialists; Pieter Sonneveld, research support from Janssen, BMS, Sanofi, and Amgen, all for EMN trials; participating in advisory boards for Janssen, BMS, Sanofi, Amgen, Cargen, and Pfizer; Ashutosh Wechalekar, honoraria/advisory board from Janssen, Alexion, Attralus, Celgene/BMS, Takeda, and GSK; Efstathios Kastritis, honoraria/advisory board from Genesis Pharma, Janssen, GSK, and Pfizer; research support from Amgen, Janssen, and Pfizer., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pomalidomide demonstrated activity in the treatment of AL amyloidosis in three phase II clinical trials. We evaluated the safety and efficacy of 28-day cycles of pomalidomide and dexamethasone in 153 previously treated patients with systemic AL amyloidosis. Ninety-nine (65%) were refractory to the last line of therapy and 54 (35%) had relapsed. The median number of previous lines of therapy was 3 (range: 2-7): 143 patients (93%) previously received bortezomib, 124 (81%) lenalidomide, 114 (75%) oral melphalan, and 37 (24%) underwent autologous stem cell transplant. At the completion of cycle 6, 68 (44%) patients obtained at least partial haematologic response, with 5 complete responses (CR, 3%), 35 very good partial responses (VGPR, 23%). Haematologic response resulted in improved overall survival (median survival 50 vs. 27 months, p  = .033) in a 6 months landmark analysis. Obtaining at least partial response was also associated with a significant improvement of the progression-free survival (median PFS 37 vs. 18 months, p  < .001). Pomalidomide is an effective treatment for heavily pre-treated patients with AL amyloidosis. Haematologic responses are associated with an overall survival advantage.

Although high-dose therapy and autologous stem cell transplant combined with novel agents continues to be the hallmark of first-line treatment in newly diagnosed transplant-eligible multiple myeloma patients, the impact of tandem autologous or autologous/reduced-intensity allogeneic transplant for patients with extramedullary disease (EMD) and high-risk cytogenetics is not yet defined. Here, we analyzed clinical and cytogenetic data from 488 adult myeloma patients with EMD undergoing single autologous (n = 373), tandem autologous (n = 84), or autologous-allogeneic transplant (n = 31) between 2003 and 2015. At least 1 high-risk abnormality was present in 41% (n = 202), with del(17p) (40%) and t(4;14) (45%) the most frequent. More than 1 high-risk abnormality was found in 54%. High-risk cytogenetics showed worse 4-year overall survival (OS) and progression-free survival (PFS) of 54% and 29%, respectively, versus 78% and 49% for standard-risk cytogenetics (P < .001). Co-segregation of high-risk abnormalities did not seem to affect outcome. Regarding transplant regimen, OS and PFS were 70% and 43% for single autologous versus 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic (P = .06 and P = .30). In multivariate analysis high-risk cytogenetics were associated with worse survival (hazard ratio [HR], 2.00; P = .003), whereas tandem autologous significantly improved outcome versus single autologous transplant (HRs, .46 and .64; P = .02 and P = .03). Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival, but results were limited because of small population (HR, .31). In conclusion, high-risk cytogenetics is frequently observed in newly diagnosed myeloma with EMD and significantly worsens outcome after single autologous, whereas a tandem autologous transplant strategy may overcome onset poor prognosis., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Allogeneic stem cell transplantation is a therapeutic option under dispute but nonetheless chosen with increasing frequency for patients suffering from multiple myeloma in Europe. To study possible predictors of survival, 79 patients were investigated using whole-body magnetic resonance imaging to assess the visible tumor burden before and after allogeneic stem cell transplantation. Statistical analysis of clinical and imaging parameters included Cox regression models and distribution of survival time estimates (Kaplan-Meier method). Log rank test was used to determine the prognostic impact of the presence of focal lesions on survival. A higher tumor burden according to the lesion count was associated with a shorter overall survival (univariable/multivariable Cox regression: 1 st magnetic resonance imaging P =0.028/ P =0.048; 2 nd magnetic resonance imaging P =0.008/ P =0.024). Focal infiltration pattern itself seemed to be an additional adverse prognostic factor for overall survival (2 nd MRI P =0.048), although no definite cut-off could be defined. Kaplan-Meier estimates at 60 months of follow up show a significant difference (Log rank P =0.04) for overall survival rates between patients with focal infiltration (32%) and those without (75%). Since this subgroup of patients may benefit from maintenance therapy, adoptive immunotherapy, or local interventions, whole-body imaging is an appropriate and highly recommendable diagnostic approach for detection of prognostically relevant lesions before and after treatment., (Copyright© 2018 Ferrata Storti Foundation.)