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Background: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis., Methods: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model., Results: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P =0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P =0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P =0.89)., Conclusions: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell dyscrasia without standard front-line treatment. Merely, few studies have reported the responses and outcomes of bortezomib plus dexamethasone (BDex) in POEMS syndrome. In this study, a total of 69 patients (40 males) treated with front-line BDex were included. The median age at diagnosis was 50 years (range, 30-78 years). After a median of 9 cycles BDex (range 1-9), fifty-two (88.1%), thirty-two (46.4%), and forty-seven (71.2%) patients achieved the best neurologic response, hematological complete response, and serum vascular endothelial growth factor (VEGF) response, respectively. The extravascular overload, pulmonary hypertension, and renal impairment also substantially improved. No treatment-related death occurred. Two patients developed grade-1 bortezomib-induced peripheral neuropathy and were reversible after drug withdrawal. After a median follow-up of 22.5 months, the estimated 2-year overall survival and time to next treatment were 95.7% and 65.6%, respectively. In conclusion, the combination of bortezomib and dexamethasone is effective, with a high response rate and safety profile for patients with newly diagnosed POEMS syndrome., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To explore the clinical characteristics and outcomes in Chinese patients with type I cryoglobulinemia (CG), we retrospectively analyzed the clinical data, management, and outcomes of 45 patients diagnosed with type I CG in our hospital from January 2015 to March 2019. In our study, all type I CGs were secondary to hematologic diseases, and monoclonal gammopathy of unknown significance was the most common primary disease, accounting for 48.9% (n = 22). Additionally, B cell non-Hodgkin lymphoma, Waldenström's macroglobulinemia, and multiple myeloma accounted for 24.4% (n = 11), 20.0% (n = 9), and 6.7% (n = 3), respectively. In patients with type I CG, skin damage was the most common symptom, presenting in 57.8% of the patients, followed by peripheral neuropathy (22.2%) and renal involvement (15.6%). Treatment was initiated in 29 patients (64.4%), and the most common choice was a rituximab-based regimen in 13 patients (44.8%), followed by bortezomib-based regimen in 11 patients (37.9%). Clinical symptoms were significantly improved after treatment, and the clinical remission rate was 86.2%, including 34.5% of complete clinical remission, while the laboratory response rate was 88.9%, including 33.3% of complete response and 55.6% of partial response. The expected 1-year overall survival was 97.8%. In conclusion, for patients with multisystemic involvement, such as skin damage, kidney damage, or peripheral neuropathy, the diagnosis of type I CG should be considered, and the underlying disease needs to be explored. Symptoms and primary diseases should be taken into consideration before choosing initial management.

Background: Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of AL amyloidosis, but the benefits of bortezomib in patients with ultra-high-risk (2004 Mayo stage IIIb or 2012 Mayo stage IV) AL amyloidosis have not been proved definitively. Methods: We performed a retrospective analysis of patients newly diagnosed with ultra-high-risk AL amyloidosis who received a bortezomib-based regimen or supportive treatment. We aimed to establish the effects of bortezomib on early mortality and long-term outcomes in this high-risk population. Results: Patients receiving bortezomib-containing chemotherapy ( n  = 62) and patients receiving no chemotherapy ( n  = 24) were included. Median overall survival (OS) was 30 months in the bortezomib group and 2 months in the control group ( p  < .001), and median progression-free survival (PFS) was 15.8 months (bortezomib) and 2 months (control; p  < .001). The early-death rate (within 6 months of treatment) was 32.3% (bortezomib) and 66.7% (control; p  < .001). In a landmark analysis assessing outcomes in patients surviving beyond 6 months, the 2-year OS and PFS in the bortezomib group were 77.3% and 65.8%, respectively. Conclusions: Bortezomib-based regimens can help to reduce early mortality and improve long-term survival in patients with ultra-high-risk AL amyloidosis.

Light chain-associated Fanconi syndrome (LCFS) is a disorder of renal proximal tubule due to immunoglobulin light chains. Cases of LCFS are rare and mostly sporadically reported, and treatment of this entity is still controversial. This single-center retrospective study included 22 patients diagnosed with LCFS in Peking Union Medical College Hospital. Monoclonal gammopathy of undetermined significance was diagnosed in 13 patients, and overt multiple myeloma in six patients, with two smoldering myeloma and one Waldenstrom macroglobulinemia. Light chain was mostly kappa type (90.9%). Baseline median estimated glomerular filtration rate was 66 (13-126) ml/min/1.73 m 2 , with one patient presented as end-stage renal disease. After a median follow-up of 37 months, three patients died. Twelve patients were treated with chemotherapy, including 7 with bortezomib-based regimens. Renal function was significantly improved in the group of patients who received chemotherapy (p = 0.026). Compared with other chemotherapy regimens, patients with bortezomib-based treatment had a better hematological response (p = 0.027) as well as a better proximal tubule outcome (p = 0.015). Chemotherapy likely outweighs supportive treatment in patients with LCFS. Bortezomib-based regimen seems to be a safe first-line therapy for management of those patients.

Cryoglobulinemic vasculitis is a rare and frequently fatal type of myocarditis. Cardiac manifestations in type 1 cryoglobulinemic vasculitis have never been reported to our knowledge. We report a rare case of type 1 cryoglobulinemic vasculitis with cardiac involvement in a patient who experienced progressive heart failure during the diagnosis. The diagnosis was made by the presence of cryoglobulins and endomyocardial biopsy results. After bortezomib-containing treatments, plasma cryoglobulin levels returned to normal, and the patient's clinical condition gradually improved., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

AL amyloidosis is a rare plasma cell dyscrasia characterized by multi-organ involvement and poor prognosis. We retrospectively evaluated the organ response (OR) and long-term survival of newly diagnosed AL amyloidosis patients who received first-line bortezomib-containing induction therapy, aiming to identify the clinical indication of a 50% reduction in the difference between involved and uninvolved free light chains (dFLC) after first cycle of treatment. Among the 89 patients included, 78.7% had cardiac involvement and 42.7% were diagnosed with 2004 Mayo stage III disease, while 75.3% of patients achieved a hematological response, including 37.1% with complete response and a median response time of 1 month. Cardiac and renal responses were observed in 44.3 and 53.1% of patients, respectively. Sixty-one (68.5%) patients achieved at least 50% reduction in dFLC after the first cycle of therapy. After a median follow-up duration of 12 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 61.3 and 61.7% respectively. At least 50% reduction in dFLC after the first cycle of therapy was predictive of achieving an OR (p = 0.002), as well as superior PFS (HR = 0.119; 95% CI = 0.045-0.313; p < 0.001) and OS (HR = 0.206; 95% CI = 0.078-0.541; p = 0.001). Additionally, the median PFS and OS were not reached for patients with rapid reduction of dFLC. These results demonstrated that early reduction of dFLC after the first cycle of treatment is predictive of achieving an OR and long-term survival in AL patients receiving bortezomib.

Considering the adverse outcomes of these patients, Mayo 2004 stage IIIb patients were not included in most clinical trials. (B) Survival of Mayo 2004 stage IIIb AL amyloidosis patients categorized by treatment (bortezomib-based regimen, immunomodulator (IMID) or melphalan combination and supportive care group). Among patients with available clinical assessments ( I n i = 69), the overall response rate was 52.2% ( I n i = 36), with 22 patients (31.9%) achieving a complete response (CR) and 8 patients (11.6%) achieving a very good partial response (VGPR). [Extracted from the article]

Relapsed and refractory (R/R) idiopathic Multicentric Castleman disease (iMCD) is a clinical challenge with few treatment options. In this first multicenter, prospective trial which implemented the recently published CDCN response criteria, we evaluated the efficacy and safety profiles of bortezomib-cyclophosphamide-dexamethasone (BCD) regimen in 24 R/R iMCD patients. By 6 months, 15 patients (62.5%) achieved overall treatment responses; four patients (16.7%) had stable disease and five patients (20.8%) suffered from progression of disease. Even when considering all patients, there were significant (p <.05) improvements in median symptom score, hemoglobin, platelet count, C-reactive protein (CRP) erythrocyte sedimentation rate (ESR), IL-6, albumin, and immunoglobin G (IgG) after treatment. The regimen was well tolerated without grade 3 or higher adverse events. Estimated 1-year progression-free survival (PFS) and overall survival (OS) were 79% and 92%, respectively. BCD regimen is an effective and safe treatment option for R/R iMCD patients. This trial was registered at as # ChiCTR1800019342. [ABSTRACT FROM AUTHOR]

Recently, a difference between involved and uninvolved free light chains (dFLC) less than 10 mg/L after treatment (stringent dFLC response) was reported to be associated with superior survival in light-chain (AL) amyloidosis. We conducted a retrospective study of AL amyloidosis patients treated with bortezomib to investigate the predictive value of a stringent dFLC response. Two hundred and thirty-five patients were included. The cardiac and renal responses were much higher in patients achieving a stringent dFLC response (86.5% versus 42.7% and 75.9% versus 38.2%, p <.001). Patients with a stringent dFLC response had significantly longer overall survival and time to next treatment (TNT). Among the very good partial response (VGPR) patients, the TNT of stringent dFLC responders was superior to those of the remaining VGPR patients (p =.045) and comparable to those of complete response patients. In conclusion, a stringent dFLC response might be added to current response criteria for AL amyloidosis. [ABSTRACT FROM AUTHOR]