scholarly journals Two-Year Evaluation of the German Clinical Amyloidosis Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3780-3780
Author(s):  
Ute Hegenbart ◽  
Niklas Fuhr ◽  
Laura Huber ◽  
Christoph Kimmich ◽  
Kaya Veelken ◽  
...  
Keyword(s):  
Bone Scintigraphy ◽  
Cause Of Death ◽  
Outpatient Clinic ◽  
Research Funding ◽  
Tissue Sample ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Inclusion Criteria ◽  
Attr Amyloidosis ◽  
Staging Systems

Abstract Introduction Currently there are no sufficient epidemiology data on systemic amyloidosis in Germany. Our aim was to collect epidemiological data on amyloidosis diseases to determine incidence and distribution of amyloidosis types in Germany. In addition, data on diagnosic pathways, demographic, clinical and biological factors, quality of life (Qol) and overall survival (OS) have been collected. Methods: The actual registry population consists of the first n=1000 reported cases of newly diagnosed amyloidosis patients between 4.1.18 - 21.11.19. Data cutoff of the analysis was June 30, 2021. Patients were included in the registry by two main ways: personal presentation at the amyloidosis outpatient clinic or phone contact of the attending physician to the Amyloidosis Center. Inclusion criteria were either a Congo Red positive tissue sample or unequivocal findings in bone scintigraphy (ATTR amyloidosis). Patients were contacted every 6 months to obtain QoL data using EORTC QLQ-C30, EQ-5D-5L and SF36-v2 questionnaires. This registry was financially supported by Prothena. Results: During this time period 963 of the first 1000 reported newly diagnosed patients (37 pts. did not fulfil inclusion criteria and were excluded) were evaluated mainly through the amyloidosis outpatient clinic (n=581, 60.3%). Seventy-three percent of cases were male (n=706). The median age at diagnosis was 71 years and differed between the AL pts.(65,5 years) and ATTRwt (78 years) patients. The subgroup distribution was as follows: 438 (45,5%) AL pts., 318 (33%) ATTRwt pts., 35 (3,6%) ATTRv pts, 60 (6,2%) ATTR of unknwon subtype, 66 (6,8%) local amyloidosis, 30 (3,1%) AA amyloidosis, 12 (1,2%) others and 4 (0,4%) not typed. Diagnosis was confirmed by biopsy in 88% and in 12% by bone scintigraphy. The most commonly involved organs were heart (n=733, 76,1%) and kidney (n=305, 31,7%). Cardiac staging systems were used for systemic AL (Kumar et al., 2014) with heart involvement and ATTR amyloidosis (Gillmore et al., 2018). Data on survival were available in all cases (median follow-up 27 months). During the observation time 249 patients died (60 ATTRwt and 153 AL pts., 36 other, figure). The most frequent cause of death was amyloidosis itself (n=191, 76,7%). Seven (2,8%) patients died due to therapeutic complications. Compared to ATTRwt patients with cardiac AL amyloidosis had a higher hazard to die, 1 year survival was 78.96% (95% CI 75.23% - 82.88%) compared to 94.30% (95% CI 91.80% - 96.90%), respectively. In multivariate analysis (including age, cardiac staging systems and time from symptoms to diagnosis) factors associated with worse OS were increasing age for AL pts. (HR 1.04, p<0,001 for AL, and highest cardiac stage (HR 2.33, p=0,001 for AL and 5.69, p<0,001 for ATTRwt). Conclusion: The first 2 years of the German clinical amyloidosis registry have been successful to generate valuable clinial data for all types of amyloidosis from newly diagnosed patients. Subtyping the amyloid precursor protein was successful in nearly all patients. The most common form is AL followed by ATTRwt amyloidosis. Heart involvment was very common and pts. were mostly in advanced cardiac stage. Main cause of death was amyloidosis related. In 2020 we have started an extended registry (financially supported by Janssen) including anonymized biopsy reports from reference pathologists. With this approach we will probably obtain more precise data on incidence in Germany. Figure 1 Figure 1. Disclosures Hegenbart: Alnylam: Honoraria; Akcea: Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Prothena: Research Funding. Carpinteiro: Janssen: Honoraria; BMS: Honoraria; GSK: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Müller-Tidow: Pfizer: Research Funding; Bioline: Research Funding; Janssen: Consultancy, Research Funding. Schönland: Janssen: Honoraria, Other: Travel grants, Research Funding; Prothena: Honoraria, Other: Travel grants; Pfizer: Honoraria; Takeda: Honoraria, Other: Travel grants; Sanofi: Research Funding.

scholarly journals Rapid and Deep Hematologic Responses Are Associated with Improved Major Organ Deterioration Progression-Free Survival in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ashutosh D. Wechalekar ◽  
Giovanni Palladini ◽  
Giampaolo Merlini ◽  
Raymond L. Comenzo ◽  
Arnaud Jaccard ◽  
...  
Keyword(s):  
Research Funding ◽  
Progression Free Survival ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Free Survival ◽  
Major Organ ◽  
End Stage

Background: As immunoglobulin light chains present in AL amyloidosis are considered to be toxic to involved organs, especially the heart, rapid and deep hematologic remission with reduction of these light chains with frontline therapy may be crucial to improving long-term clinical outcomes. ANDROMEDA (NCT03201965) is the first phase 3 study in this patient population to evaluate major organ deterioration progression-free survival (MOD-PFS), a composite endpoint of time to end-stage cardiac disease (requiring cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); end-stage renal disease (requiring hemodialysis or renal transplant); hematologic progression per consensus guidelines1; and death. Here, we report the impact of early and deep hematologic responses on MOD-PFS. Methods: ANDROMEDA is a randomized, open-label, active-controlled phase 3 study of patients with newly diagnosed AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (VCd) ± daratumumab subcutaneous (DARA SC; DARA 1800 mg coformulated with recombinant human hyaluronidase PH20 in 15 mL). Key eligibility criteria were newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage I-IIIA, eGFR ≥20 mL/min, and absence of symptomatic multiple myeloma. Disease evaluations occurred every 4 weeks during Cycles 1-6. Hematologic responses were adjudicated by an Independent Review Committee. Landmark analyses for response were performed at 1 and 3 months (± 7 days). Analyses of hematologic responses and MOD-PFS were performed on the intent-to-treat analysis set. Patients without a baseline or post-baseline assessment were censored at randomization for the MOD-PFS analysis. Hazard ratios and corresponding 95% confidence intervals were estimated based on Cox proportional hazard model. Results: A total of 388 patients were randomized to DARA-VCd (n=195) or VCd alone (n=193). Baseline characteristics were well balanced between groups. The proportions of patients with heart and kidney involvement were 71% and 59%, respectively. Median follow-up was 11.4 months (range, 0.03-21.3+). For the 1- and 3-month landmark analysis, hematologic response was available for 356 and 289 patients, respectively. Hematologic response rates by treatment group at 1 and 3 months are shown in the Table. MOD-PFS was longer in patients with complete response (CR)/very good partial response (VGPR) at 1 and 3 months vs patients with lower levels of response (Figure). CR/VGPR at 1 and 3 months was associated with reduced risk of death or major organ deterioration in a multivariate analysis adjusting for baseline difference between involved and uninvolved free light chains and cardiac stage, (HR: 0.399, P=0.0006 and HR: 0.262, P=0.0003, respectively). At 1 and 3 months, cardiac and renal response rates were higher in those who achieved early and deep hematologic responses (CR and VGPR). Conclusions: CR/VGPR at 1 and 3 months was associated with a reduced risk of major organ deterioration and death in patients with newly diagnosed AL amyloidosis. These data confirm that initial therapy that achieves rapid and deep hematological responses is essential to improving long-term outcomes in AL amyloidosis. Reference 1. Comenzo RL, et al. Leukemia. 2012;26(11):2317-25 Disclosures Wechalekar: Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory; Celgene: Honoraria; Takeda: Honoraria, Other: Travel. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Comenzo:Caleum: Consultancy; Unum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Jaccard:Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding; Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Pei:Janssen: Current Employment, Current equity holder in publicly-traded company. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Kastritis:Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.

scholarly journals Reducing Dependence on General Anesthesia for Pediatric Oncology Outpatients Undergoing Repeated Lumbar Punctures

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Esther R. Berko ◽  
Yahui Wei ◽  
Emily Stiglich ◽  
Derek Klingman ◽  
Julie Vardaro ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Nurse Practitioners ◽  
Outpatient Clinic ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Young Patients ◽  
Hematologic Malignancies ◽  
Newly Diagnosed ◽  
Moderate Sedation ◽  
Oral Midazolam

Introduction: A growing body of data has shown that higher cumulative anesthesia exposure is associated with neurocognitive impairment in children with chronic disease, including those with hematologic malignancies [Banerjee JAMA Oncology 2019]. To limit general anesthesia (GA) exposure alternative means of sedation and acceptance of alternatives by patients, families and providers need to be explored for children with acute lymphoblastic leukemia or lymphoma (ALL/LL) undergoing repeated lumbar punctures (LP) to deliver intrathecal (IT) chemotherapy. Methods: Patients age 1 to 25 years with ALL/LL treated at the Children's Hospital of Philadelphia main outpatient clinic (CHOP Main) and two CHOP satellite oncology offices (KOP, VOR) were analyzed for baseline rates of sedation for lumbar punctures. GA was defined as the use of intravenous (IV) propofol or an inhalational flurane. Moderate sedation was defined as IV fentanyl (maximum 2 mcg/kg dosing) for analgesia and midazolam (maximum 0.1 mg/kg) for anxiolysis. IV or oral midazolam only was considered mild sedation. We created a comprehensive quality improvement (QI) pathway to implement the use of mild/moderate sedation as a new Division of Oncology standard for LP-only procedures. Our QI goal was a 10% reduction in use of GA with concomitant measurement of outpatient clinic length of stay (LOS) as an additional metric. LOS was measured as time from triage to port de-access. Results: Our interdisciplinary QI team leveraged the CHOP QI framework utilizing tools that included a driver diagram (Figure 1) and impact/effort matrix to develop and prioritize interventions associated with achieving the QI goal. The Plan-Do-Study Act methodology was used to optimize the intervention. This required extensive collaboration with pediatric oncologists, nurse practitioners, nursing, child life, pharmacy, and QI staff to encourage methodology adoption and to optimize clinic workflow for maximal provider/patient participation and procedural efficiency. In the immediate period preceding the QI intervention (October 2019 to February 2020), baseline rates of GA use for across all 3 clinic sites were 73.1%, 15% (plus 34.6% deep sedation), and 24.7% at CHOP Main, KOP, and VNJ, respectively in 310 LP only procedures for patients with ALL/LL. After a delay in implementation due to COVID, the rate of GA usage at CHOP Main from May to July 2020 was reduced to 55.6% for 81 LPs (p=0.001) (Figure 2), while GA rates at the satellite clinics were unchanged. Decreased GA use at CHOP main was replaced by a significant increase in mild/moderate sedation (26.9% to 44.5%; p=0.001). Of the 18 newly diagnosed patients participating in the intervention to date, 16 receive their LPs with no or mild/moderate sedation. The median age of this cohort is 7 years of age with 6 patients ≤ 5 and 12 patients ≤ 10 years. The other two patients have medical syndromes deemed not conducive to replacing GA with moderate sedation. No child has experienced complications from moderate sedation or returned to GA due to sedation intolerance. Overall clinic LOS decreased significantly for all patients getting LPs (GA and sedation) (mean 4.88 hours vs 4.08 hours; p=0.033). An unintended benefit of the QI initiative is that the average LOS for patients receiving moderate sedation decreased from 6.67 hours to 4.15 hours (p=0.017) with the new streamlined clinic workflow. Conclusion: Baseline rates of sedation varied by oncology clinic site and appeared to align with ease of access to GA. GA is available in the oncology main clinic 3 days/week, and 73% of ALL/LL patients were using GA for LPs prior to the intervention. Since March 2020, nearly all patients with newly diagnosed ALL/LL are now undergoing LPs with no or mild/moderate sedation. Our data show that with appropriate education and preparation, LP with mild/moderate sedation is a feasible alternative to GA even for very young patients and reduces clinic LOS. We have expanded this QI intervention to include children with other newly-diagnosed cancers who require LPs and/or IT chemotherapy. Future directions include converting patients in ALL/LL maintenance and those undergoing other minimally invasive procedures from GA to moderate sedation. Disclosures Tasian: Incyte Corporation: Research Funding; Gilead Sciences: Research Funding; Aleta Biotherapeutics: Membership on an entity's Board of Directors or advisory committees. Rheingold:Pfizer: Research Funding.

scholarly journals Bortezomib-Based First Line Treatment for AL Amyloidosis Patients Who Are Not Candidate for Stem Cell Transplantaion

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3256-3256
Author(s):  
Joon Young Hur ◽  
Kang Kook Lee ◽  
Sang Eun Yoon ◽  
Sehhoon Park ◽  
Jangho Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
The Body ◽  
Autonomic Nerve ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment

Abstract Introduction Systemic AL amyloidosis is characterised by deposition of misfolded immunoglobulin light chains within organs. Treatment for amyloidosis is generally derived from that for multiple myeloma (MM). Combinations of immunomodulatory drugs and proteasome inhibitors are standard frontline MM therapy, but there is little experience with such regimens in AL. For patients not receiving autologous stem cell transplantation (ASCT), bortezomib-based regimens have been first-line treatment in AL amyloidosis over the last few years. The purpose of this study is to investigate the efficacy of bortezomib-based regimens for patients with newly diagnosed AL amyloidosis Methods We performed a retrospective study of all newly diagnosed patients with AL amyloidosis treated at our center between 4/1/11 and 12/31/17. Data pertaining to demographics, diagnosis, treatment and follow-up were extracted from electronic medical records. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. All statistical analyses were performed by using the SPSS 24.0 software. Time to progression (TTP) is defined as time from the date of diagnosis or the start of treatment for a disease until the disease starts to get worse or spread to other parts of the body. The primary endpoint was overall response rate and secondary endpoints were overall survival (OS) and TTP. Results A total 63 patients with newly diagnosed AL amyloidosis who did not receive ASCT were analyzed. Clinical characteristics are shown in Table 1. They included 32 men and 31 women with a median age of 66 years (range, 42-82). Autonomic nerve, Cardiac, peripheral nerve, renal, soft tissue, and liver involvement were found in 46 (73%), 41 (65.1%), 23 (36.5%), 20 (31.7%), 16 (25.4%), 4(6.4%), respectively. The Mayo 2012 stage was: Stage 2 3.8%, Stage 3 30.8% and stage 4 65.4%. Hematological responses were: complete response (CR) 33.3 %, VGPR 19.0%, partial response (PR) 12.6% and no-response (NR) 17.4%. Organ response was 26.9% (n=17). With a median follow-up of 34 months, median OS was 40 months (95% CI 30-50) (Figure 1A) and median TTP was 27 months (95% CI 18-36) (Figure 1B). The rate of early death within 6 months was 28.5% (n=18). Patients were classified according to first-line treatment; bortezomib-based regimens (VMP, n=37; VD (bortezomib and dexamethasone), n=9; VCD, n=8; VMD, n=8; VTD (bortezomib with thalidomide and dexamethasone, n=1). Hematological responses of VMP, VD, VCD, VMD, and VTD were: 75.6%, 55.5%, 50.0%, 50.0%, 100%, respectively. Organ responses of VMP, VD, and VMD were: 35.1%, 22.2%, 25.0%, respectively. Conclusions In this retrospective analysis, bortezomib-based regimens in newly diagnosed AL amyloidosis showed results that appear comparable to those seen at other centers. These findings therefore continue to support the emerging roles for bortezomib-based regimens for the purposes of improving response. Larger scale analyses in multi-center trials would be beneficial to further study these roles. Disclosures Kim: Kyowa-Kirin: Research Funding; Roche: Research Funding; Mundipharma: Research Funding; Novartis: Research Funding; Celltrion: Research Funding; J&J: Research Funding; Takeda: Research Funding.

scholarly journals Prognostic Restaging at the Time of 2nd-Line Therapy in Patients with AL Amyloidosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5594-5594
Author(s):  
Yi L. Hwa ◽  
Morie A. Gertz ◽  
Shaji K. Kumar ◽  
Martha Q. Lacy ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Mayo Clinic ◽  
Initial Treatment ◽  
Research Funding ◽  
Prognostic Value ◽  
Staging System ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Line Therapy ◽  
Staging Systems

Abstract Background: It is well known that the staging stratification at diagnosis predicts survival in immunoglobulin light chain (AL) amyloidosis, but there is a paucity of literature delineating the prognostic value of these systems at the time of 2nd-line therapy. Methods: We conducted a retrospective study to evaluate the prognostic value of AL staging among 563 patients with staging data, who initiated a 2nd-line therapy between 2000 and 2015. Both the Revised Mayo 2012 staging system and the European revision of the Mayo 2004 staging system were used. Results: The median time from initial treatment to 2nd-line therapy was 11.6 months. Median follow-up from institution of 2nd-line therapy was 54.1 months. The 1st-line therapy for patients was autologous stem cell transplant (ASCT) in 216 (38%) patients; and 2) non-ASCT therapies in 347 patients. Both staging systems were prognostic with a risk ratio of 9.4 (95%CI: 6.0, 15.1; p<0.0001) between stage IIIb and I, and of 12.2(8.1, 18.5; p<0.0001) between IV and I. At the time of 2nd-line therapy the staging systems' predictive values were independent of what the patients' 1st-line therapies had been despite the fact that the median time from initial treatment to 2nd-line therapy was 19.4 months in ASCT group and 8.0 months in non-ASCT group. Among the patients receiving 2nd-line therapy after ASCT, the 5-year overall survival (OS) from 2nd-line therapy for those with ≤ stage II versus >stage II was 65% and 31% (Mayo 2004) and 70% and 23% (Mayo 2012). The respective numbers for patients relapsing from a non-ASCT therapy were 57% and 26% (Mayo 2004) and 60% and 23% (Mayo 2012). Conclusions: This study indicates that the Mayo staging systems work well at the time of instituting 2nd-line therapy and is independent of whether 1st-line therapy was ASCT based. Figure. Figure. Disclosures Gertz: annexon: Consultancy; Medscape: Consultancy; Apellis: Consultancy; celgene: Consultancy; Prothena: Honoraria; Abbvie: Consultancy; Amgen: Consultancy; Physicians Education Resource: Consultancy; spectrum: Consultancy, Honoraria; Ionis: Honoraria; Research to Practice: Consultancy; Teva: Consultancy; janssen: Consultancy; Alnylam: Honoraria. Kumar:KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lacy:Celgene: Research Funding. Dingli:Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Russell:Vyriad: Equity Ownership. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding.

scholarly journals Subcutaneous Daratumumab (DARA SC) + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Asian Patients with Newly Diagnosed Light Chain (AL) Amyloidosis: Subgroup Analysis from the Phase 3 Andromeda Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Kenshi Suzuki ◽  
Ashutosh D. Wechalekar ◽  
Kihyun Kim ◽  
Chihiro Shimazaki ◽  
Jin Seok Kim ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Research Funding ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Duration Of Treatment ◽  
Phase 3 ◽  
Asian Patients ◽  
Kidney Involvement ◽  
Major Organ

Introduction: Systemic AL amyloidosis is a rare disorder of clonal CD38+ plasma cells characterized by deposition of insoluble amyloid fibrils leading to tissue damage and organ dysfunction. Currently, there are no health authority-approved treatments for AL amyloidosis, and standard of care (SoC) includes therapies developed for multiple myeloma (MM). DARA is a human CD38-targeting antibody for MM. Combining DARA with VCd improved outcomes for AL amyloidosis versus VCd alone in the phase 3 ANDROMEDA study. Here, we report a subgroup analysis of Asian patients (China, Japan, and Korea) from ANDROMEDA. Methods: Eligible patients had newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage (Mayo 2004) I-IIIA, eGFR ≥20 mL/min, and no symptomatic MM. Patients were randomized 1:1 to receive DARA SC plus VCd (D-VCd) or VCd. All patients received bortezomib (1.3 mg/m2 SC QW), cyclophosphamide (300 mg/m2 PO or IV QW), and dexamethasone (40 mg PO or IV QW) for six 28-day cycles with or without DARA SC (1,800 mg DARA co-formulated with recombinant human hyaluronidase PH20 [rHuPH20]; ENHANZE® drug delivery technology, Halozyme, Inc.) by injection QW in Cycles 1-2, Q2W in Cycles 3-6; after Cycle 6, patients continued DARA monotherapy as maintenance for up to 24 cycles (28-day cycles). Disease status was evaluated Q4W in Cycles 1-6 and Q8W after Cycle 7 until hematologic progression or major organ deterioration. The primary endpoint was overall hematologic complete response (CR) rate; key secondary endpoints included major organ deterioration progression-free survival (MOD-PFS), survival, and safety. MOD-PFS was defined as the time from randomization to any of the following events (whichever occurred first): death, clinical manifestation of cardiac or renal failure, or hematologic progression. Results: Among 388 randomized patients (D-VCd, n=195; VCd, n=193), 60 were Asian (D-VCd, n=29; VCd, n=31). Baseline characteristics were well balanced between arms and consistent with the intent-to-treat population. The median age was 66 years, 70% and 58% had heart and kidney involvement, respectively, and 60% had ≥2 organs involved. Cardiac stage I, II and IIIA/B were 28%, 28%, and 43%, respectively. The median duration of treatment was 9.2 mo for D-VCd and 5.3 mo for VCd. Median follow-up was 9.4 mo. The overall hematologic CR rate was 59% for D-VCd and 10% for VCd (odds ratio, 13.2; 95% CI, 3.3-53.7; P&lt;0.0001). D-VCd vs VCd achieved higher rates of very good partial response or better (≥VGPR; 93% vs 61%). MOD-PFS favored D-VCd-treated patients (HR 0.21; 95% CI, 0.06-0.75, P=0.0079). A total of 12 deaths occurred (D-VCd, n=3; VCd, n=9). The most common (≥10%) grade 3/4 TEAEs were lymphopenia (D-VCd 35%/VCd 32%), neutropenia (10%/3%), diarrhea (10%/7%), pneumonia (7%/10%), cardiac failure (7%/10%), hypokalemia (7%/10%), anemia (3%/10%), thrombocytopenia (3%/10%), hypoalbuminemia (3%/10%), and syncope (3%/10%). TEAEs leading to treatment discontinuation occurred in 1 patient in each treatment arm. Conclusion: The addition of DARA SC to VCd was superior to VCd alone in Asian patients, resulting in deeper hematologic responses and improved clinical outcomes, including MOD-PFS, with a safety profile consistent with the overall study population. These data support the use of D-VCd in Asian patients with newly diagnosed AL amyloidosis. Disclosures Suzuki: Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Takeda, Amgen, Janssen and Celgene: Consultancy; Bristol-Myers Squibb, Celgene and Amgen: Research Funding. Wechalekar:Janssen, Takeda, Caelum, Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:BMS, Takeda, Amgen, Celgene, Janssen: Consultancy, Honoraria, Research Funding. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Zhou:Peking University First Hospital: Current Employment. Iida:Celgene: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Chugai: Research Funding; Kyowa Kirin: Research Funding; AbbVie: Research Funding; Merck Sharpe Dohme: Research Funding; Janssen: Honoraria, Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Qin:Janssen: Current Employment. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Comenzo:Amgen: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Caleum: Consultancy; Karyopharm: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria, Other: Travel/accommodations/expenses; Janssen: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding; Pfizer: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel/accommodations/expenses. OffLabel Disclosure: To evaluate the efficacy and safety of daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with AL amyloidosis.

scholarly journals Epidemiology of Light-Chain Amyloidosis: A Population-Based Cohort Study in Taiwan

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1637-1637
Author(s):  
Hsin-An Hou ◽  
Chao-Hsiun Tang ◽  
Choo Hua Goh ◽  
Sarah Siggins ◽  
Shih-Pei Shen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Mortality Rate ◽  
Light Chain ◽  
Research Funding ◽  
Population Based ◽  
Advisory Board ◽  
Al Amyloidosis ◽  
Prevalence Rates ◽  
Newly Diagnosed ◽  
All Cause Mortality

Abstract Introduction: AL (light-chain) amyloidosis is a rare disease with an incidence rate of approximately 12-13 per million population in Western countries. To date, the epidemiology of AL amyloidosis in Asian countries has not been described. Population-based clinical information about AL amyloidosis is needed to understand disease characteristics and the impacts of future treatments on the disease Methods: We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database (NHIRD) and Death Registry to estimate the incidence, prevalence, all-cause mortality rate and characteristics of patients with AL amyloidosis in Taiwan. All patients with confirmed newly diagnosed AL amyloidosis (ICD-10 E85.4: Organ-limited amyloidosis, E85.8: Other amyloidosis and E85.9: Amyloidosis, unspecified) from 01 January 2016 until 31 December 2019 were enrolled. Eligible patients had a biopsy record within 12 months prior to, or up to 6 months after the date of diagnosis of AL amyloidosis; and at least two consecutive outpatient claims and/or one inpatient claim amyloidosis in the NHIRD. Patients were followed up until dis-enrolment, death or study end (31 December 2019), whichever occurred first. Results: A total of 841 patients with newly diagnosed AL amyloidosis were identified in Taiwan during the period 01 January 2016 until 31 December 2019. The median age at diagnosis was 61.4 years and 58.7% were men. At diagnosis, cardiac disease was present in 28.54%, renal-related disease in 23.19% and had 7.85% had multiple myeloma (Table). The crude annual incidence of AL amyloidosis was 8.46 per million population in 2016 and 8.31 per million population in 2019 (Figure). The age-adjusted incidence rates were 5.73 and 5.26 per million population, respectively. The crude and age-adjusted prevalence rates of AL amyloidosis remained similar over the study period: the crude prevalence rates were 121 to 142 per million population, and age-adjusted prevalence rate were 81.52 to 99.84 per million population. The all-cause mortality rate ranged from 1.7 to 2.9 per 1000 patients over the study period but was highest (~10 per 1000) in patients aged ≥80 years. There were 501 patients (59.6%) with a biopsy report prior to the AL diagnosis index date. Presenting clinical symptoms were not available in the claims database so we assessed the time period from biopsy to diagnosis. The median time from biopsy until diagnosis was 3.8 months and was longer than 12 months in some patients, with little change observed from year to year. Conclusion: To our knowledge, this is the first known population-based cohort study of non-hereditary amyloidosis in Asia. The incidence of AL amyloidosis in Taiwan appears to be similar to Western countries with higher prevalence in Asia. There was no apparent change in the incidence or prevalence rates over the 4 years of the study. Diagnostic delay is recognized as an important limitation in the treatment of AL amyloidosis. Figure 1 Figure 1. Disclosures Goh: Janssen: Current Employment. Siggins: Janssen Pharmaceuticals: Current Employment. Qiu: Janssen Research & Development LLC: Current Employment, Current holder of individual stocks in a privately-held company. Chou: Abbvie: Honoraria, Other: Advisory Board, Research Funding; Celgene: Honoraria, Other: Advisory Board, Research Funding; IQVIA: Honoraria, Other: Advisory Board; Pfizer: Honoraria, Other: Advisory Board; Novartis: Honoraria, Other: Advisory Board; Bristol Myers Squibb: Honoraria, Research Funding; Kirin: Honoraria, Research Funding. Liu: Janssen Research & Development LLC: Current Employment, Current holder of individual stocks in a privately-held company.

scholarly journals Induction with Bortezomib and Dexamethasone (BD) Followed By Risk Adapted High Dose Melphalan and Autologous Stem Cell Transplantation and BD Consolidation in Patients with AL Amyloidosis: A Phase II Feasibility Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3178-3178 ◽  
Author(s):  
Heather Landau ◽  
Nicole Montanez ◽  
Alexandra Cowan ◽  
Hoover Elizabeth ◽  
Carlos Flombaum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Research Funding ◽  
Treatment Initiation ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Weekly Schedule ◽  
Newly Diagnosed ◽  
Critical Determinant

Abstract Background: The depth and durability of hematologic response is a critical determinant of outcome in patients (pts) with light chain (AL) amyloidosis. Complete hematologic remissions (CR) following risk-adapted melphalan and stem cell transplant (RA-SCT) in pts with AL amyloidosis is associated with organ improvement and extended overall survival (OS). We have previously shown that using bortezomib and dexamethasone (BD) as consolidation following RA-SCT is associated with deeper hematologic responses and favorable outcomes. We have conducted a prospective phase II trial using BD as induction followed by RA-SCT and BD consolidation to determine the safety and hematologic and organ response rates of this treatment program for newly diagnosed, transplant-eligible pts with AL amyloidosis. Methods: Untreated pts with AL amyloidosis received 1-3 cycles of BD (B 1.3mg/m2, IV/SC, and D 40mg, IV/PO, days 1, 4, 8, 11). BD was discontinued before 3 cycles in patients who achieved CR. Pts were then assigned melphalan 100, 140 or 200mg/m2 based on age, renal function and cardiac involvement; Starting 3 months following RA-SCT, pts received six cycles of BD (B 1.3mg/m2, IV/SC and D 20mg, IV/PO days 1, 8, 15, 22) every 12 weeks as consolidation. Hematologic responses were assessed using International Society of Amyloidosis criteria (Palladini et al. JCO 2012) and organ responses using updated criteria (Palladini et al. Blood 2014), after induction, 3 months post RA-SCT, and at 12 and 24 months from treatment initiation. Patients with New York Heart Association Class III/IV heart failure, ECOG > 2 or > grade 2 neuropathy were ineligible. Results: Twenty pts, 70% male, with a median age of 60.1 years with renal (55%), cardiac (65%), liver/GI (15%) or nervous system (15%) involvement received BD induction and 18 patients have been transplanted. Two pts with cardiac disease died during BD induction (10% TRM); 85% of pts are alive with a median follow up of 28 mo. By intent to treat, 60% and 70% of patients achieved at least a very good partial response (>VGPR) following BD induction and RA-SCT, respectively. Overall, 95% of patients achieved hematologic responses (>PR) including 35% CR. Cardiac and renal responses were seen in 75% (N=8) and 60% (N=10) of evaluable pts at 1 year following treatment initiation. Most common grade >3 adverse events included GI (40%), Renal (30%), infectious (10%), and cardiovascular (10%); Grade 2 or higher neuropathy was seen in 40% of pts and warranted discontinuation of BD consolidation in 35% of pts. Conclusion: In newly diagnosed AL amyloidosis pts, BD induction followed by RA-SCT was safe and rapidly and effectively induced responses resulting in organ improvement. There was 10% TRM during BD induction and no deaths during transplant supporting the notion that early mortality in newly diagnosed AL pts is independent of treatment received. The high incidence of neuropathy may be related to the administration of BD on a twice weekly schedule and rendered some pts ineligible for post-transplant therapy. Whether transplant-eligible pts will ultimately derive more benefit from proteasome inhibitor induction versus consolidation is worthy of further study. Disclosures Landau: Spectrum Pharmaceuticals: Honoraria; Janssen: Consultancy; Janssen: Consultancy; Prothena: Consultancy, Honoraria; Takeda: Research Funding; Onyx: Honoraria, Research Funding. Landgren:Celgene: Honoraria; International Myeloma Foundation: Research Funding; BMJ Publishing: Consultancy; Onyx: Research Funding; Onyx: Consultancy; BMJ Publishing: Honoraria; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Medscape: Consultancy; Medscape: Honoraria; Bristol-Myers Squibb: Honoraria; Onyx: Honoraria. Giralt:TAKEDA: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding; SANOFI: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding. Hassoun:Novartis: Consultancy; Takeda: Research Funding; Celgene: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees.

Soluble ST2 (sST2) Is a Novel Valuable Prognostic Marker Among Patients With Immunoglobulin Light Chain (AL) Amyloidosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3095-3095 ◽  
Author(s):  
Angela Dispenzieri ◽  
Amy K. Saenger ◽  
Shaji K. Kumar ◽  
Morie A. Gertz ◽  
Martha Q Lacy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Research Funding ◽  
Troponin T ◽  
High Sensitivity ◽  
Staging System ◽  
Cardiac Biomarkers ◽  
Al Amyloidosis ◽  
Prognostic Information ◽  
Soluble St2 ◽  
Staging Systems

Abstract The use of soluble cardiac biomarkers such as NT-proBNP and troponin has revolutionized prognostication for patients with AL amyloidosis and led to their use in the Mayo 2004 and 2012 staging systems. Novel soluble markers with different phenotypic targets may further improve this approach. Soluble ST2 (sST2), which is the circulating form of the IL-33 receptor, has been shown to be a marker of cardiac remodelling and fibrosis, is predictive of mortality in patients with congestive heart failure, and is predictive of risk of GVHD and GVHD mortality. Samples of blood of patients with AL amyloidosis collected and frozen at -20C under a biobank IRB protocol were retrieved and sST2 measured. Patients were eligible for present study if they had a research sample collected within 90 days of their AL amyloidosis diagnosis. We have validated that values do not change significantly with storage at -20C over a 90 day period. Concentrations of sST2 were determined using a novel high-sensitivity sandwich immunoassay (Presagew ST2; Critical Diagnostics, San Diego, CA, USA). The sST2 assay had within-run and total coefficients of variation of <7.5% and 13.0% across its measurement range. Samples from 273 consecutive patients meeting diagnostic criteria for AL amyloidosis seen at our institution from 1/9/2010 to 12/22/2011 were evaluated. Median age was 63. 58% were male. One hundred and thirty have died over 33.9 months. Correlation between sST2 and the other biomarkers was modest with correlation coefficients of 0.48 and 0.20 for NT-proBNP and Troponin T, respectively. Patients with sST2 above and below the median of 27.2 ng/mL (6.3-596) had significant differences in 2 year overall survival: 71.2% to 39% (figure). In multivariate modeling sST2’s prognostic value was independent of the Mayo 2004 and the Mayo 2012 cardiac biomarker staging systems, the latter of which also includes prognostic information relating to plasma cell burden. In these multivariate models, sST2 median had a RR of 2.4, (95%CI 1.6, 3.6 p<0.001) with the Mayo 2004 Staging system (RR of 2.9, 95%CI 2.1, 4.1p<0.001); and sST2 median had a RR of 2.2 (95%CI 1.5, 3.4, p<0.001) with the Mayo 2012 staging system (RR 1.9, 95%CI 1.6, 2.3, p<0.001). A larger cohort including patients with longer follow up will be presented at the meeting as will gender specific cut off values and a comparison of our values with those previously used to prognosticate in patients with heart failure. sST2 appears to be a novel powerful prognostic factor for patients with AL amyloidosis. Because sST2 functions as a decoy receptor, which neutralizes the benefits of IL-33, it may play a role in the deleterious phenotype seen in patients with AL, i.e. myocardial hypertrophy and reduction of contractility. Disclosures: Saenger: Critical Diagnostics : Research Funding; Roche: Research Funding. Jaffe:Critical Diagnostics: Consultancy, Research Funding; Roche: Consultancy.

Comparison of Sequential Vs Alternating Administration of Bortezomib, Melphalan, Prednisone (VMP) and Lenalidomide Plus Dexamethasone (Rd) in Elderly Pts with Newly Diagnosed Multiple Myeloma (MM) Patients: GEM2010MAS65 Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 178-178 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Joaquin Martinez-Lopez ◽  
Miguel-T Hernandez ◽  
Rafael Martinez ◽  
Laura Rosiñol ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Al Amyloidosis ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Sequential Approach ◽  
Grant Support ◽  
Similar Survival

Abstract Background: VMP and Rd are two of the most effective regimens in the treatment of elderly newly diagnosed MM pts. In order to further improve its outcome, one possibility would be to use regimens including all these drugs simultaneously, but this may result toxic. Alternatively, the use of these regimens (VMP and Rd) in a sequential or alternating scheme could improve the treatment of these pts. We hypothesized the alternating scheme would minimize the emergence of resistant clones, and would reduce the cumulative toxicity. In order to test this hypothesis we decided to compare VMP and Rd in a sequential vs an alternating scheme. Pts and methods: 242 pts were randomized to receive a sequential scheme consisting on 9 cycles of VMP followed by 9 cycles of Rd or the same regimens in an alternating approach (one cycle of VMP alternating with one Rd, up to 18 cycles. VMP included the iv administration of weekly bortezomib (except in the first cycle that was given twice weekly) at 1.3 mg/m2 in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 once daily on days 1–4. Rd treatment consisted on lenalidomide 25 mg daily on days 1-21 plus dexamethasone 40 mg weekly. Results: 233 pts were evaluable for safety and efficacy (118 in the sequential and 115 in the alternating arm). Both arms were well balanced according to the baseline characteristics. Of note, 55% of pts in the sequential and 44% in the alternating arm were older than 75 yrs. Fifty-one percent in the sequential arm and 52% in the alternating had high risk cytogenetic abnormalities (t(4;14), t(14;16), del17p or 1q gains). After 9 cycles, the sCR/CR rate was lower in the sequential (20%) than in the alternating arm (32%)(p=0.02). However, among the 179 pts that were evaluable for efficacy after the 18 planned cycles of treatment, the pattern reversed: 51% achieved sCR/CR in the sequential vs 38% in the alternating arm (p=0,05). The flow-CR rate among patients in sCR/CR was 66% and 48% in the sequential vs alternating arms, respectively (P=0.16). To achieve flow-CR was associated with a significantly longer TTP (median not reached vs 15 months since the end of treatment; P=.01). After a median f/u of 27 months, median PFS was of 30 months in both sequential and alternating arms (p=NS). Median OS has not been reached, and 68% and 67% of pts are alive at 3 yrs (p=NS). Pts who achieved sCR/CR had significantly longer PFS and OS as compared with pts who did not (3-yrs PFS for sCR/CR of 76% vs 18% for <CR (p<0.0001), and 3-yrs OS of 94% vs 53% for sCR/CR vs <CR (p<0.0001)) in both arms. The achievement of flow-CR has been also associated with 3-yrs PFS of 84% vs 38% months for pts who did not achieve flow-CR. This benefit has been observed in both arms. Pts younger than 75 yrs showed a significantly longer survival as compared to pts ≥75y (3-yrs PFS of 55% vs 27m, p=0.04) and 3-yrs OS of 89% vs 35m, p<0.0001 ) , with no significant differences between sequential and alternating arms. No differences were observed in overall response rates and sCR/CR rates in standard and high risk pts, but there was a trend toward shorter PFS and OS in the subgroup of high-risk CA (median PFS of 28 months and 3-yrs OS of 64%, pNS) vs standard-risk (3-yrs PFS of 54% and 3-yrs OS of 80%, pNS). Regarding hematologic toxicity, no significant differences were observed between the sequential and alternating arms in the frequency of G3-4 neutropenia (19% and 22%) or thrombocytopenia (21% and 20%). Concerning non-hematologic toxicity, 3% and 6% of the pts in the sequential and alternating arms had G3-4 infections. No differences were observed neither in the the incidence of peripheral neuropathy in the sequential and alternating arms (4% and 3%, respectively) nor in the rate of grade 3-4 thrombotic events (1% and 2%). The rate of early discontinuations (15%) and deaths (4%) before the cycle 9 were identical in both arms; of note 71% of early discontinuations occurred in pts aged over 75 yrs and all early deaths but one were also in pts older than 75 yrs. Conclusions: The alternating regimen has demonstrated to be not superior to the sequential approach. Toxicity profile is acceptable. This Total Therapy approach, including the four active anti-myeloma agents (melphalan, bortezomib, lenalidomide and steroids) is particularly active in pts between 65-75 years old, with similar survival to that of transplant candidate pts with outstanding outcome when sCR/CR is achieved. Disclosures Mateos: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide as first-line combination therapy for AL amyloidosis.. Rosiñol:Janssen: Honoraria; Celgene: Honoraria. Ocio:Celgene Corporation: Honoraria, Research Funding. Pérez de Oteyza:Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Oriol:Celgene Corporation: Consultancy. De La Rubia:Janssen: Honoraria; Celgene: Honoraria. Bladé:Janssen: Grant support Other, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Grant support, Grant support Other, Honoraria, Membership on an entity's Board of Directors or advisory committees. Lahuerta:Janssen: Honoraria; Celgene: Honoraria. San Miguel:Janssen: Honoraria; Celgene: Honoraria.

Bortezomib-Containing Regimens for the Treatment of Newly Diagnosed AL Amyloidosis: Experience of Two Centers in Canada

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2131-2131 ◽  
Author(s):  
Hatem Alahwal ◽  
Kevin W. Song ◽  
Peter Duggan ◽  
Heather J. Sutherland ◽  
Paola Neri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Light Chain ◽  
Cardiac Disease ◽  
Research Funding ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Dismal Prognosis ◽  
Organ Response ◽  
The Impact

Abstract Introduction Bortezomib is a novel, dipeptide boronic acid molecule that has shown anti-tumor activity against Multiple Myeloma (MM) and more recently has been demonstrated to be efficacious in the treatment of Light-chain Amyloidosis (AL). Bortezomib-based regimens have changed the landscape of the treatment of AL Amyloidosis due to high levels of response as well as the adequate tolerance. Based on the above mentioned, we aimed to assess the role of Bortezomib-containing regimens (BCR) for the treatment of newly diagnosed AL amyloidosis. Methods 80 consecutive patients have been treated with bortezomib-containing regimens at BCCA and TBCC in Calgary, AB and Vancouver, BC, Canada from 01/2010 to 01/2016. Among these cases, 51 (63.8%) have received CyBorD, 19 (23.7%) bortezomib (1.3 mg/m2) and dexamethasone and the rest Bortezomib in different combinations (Table 1). The primary objective of the study was to assess hematological and organ response. Results Clinical characteristics are shown in Table 1. Median age at diagnosis was 66 years and 51.1% of patients were male. At the time of analysis, 56 patients are still alive and 14 patients have already progressed. A HR was seen in 65/72 evaluable patients (ORR, 90%) after a median of 6 cycles (range, 1-24). Fourteen patients (17.5%) did not have measurable disease based on light chain levels. CR (34.7%) and VGPR (26.4%) were seen in 61% of cases. Organ response was achieved in 49% of cases. Cardiac response was observed in 40% of cases. Median OS and PFS have not been reached (Estimate, 67 and 41 months, respectively). (Fig 1a) However, OS was shorter in the group with severe heart involvement (NT-pro-BNP>5000 or BNP>1100) (p=0.03) (Fig 1b). In conclusion, BCR are efficacious for the treatment of newly diagnosed AL Amyloidosis, providing with a high degree of organ and hematological responses. The impact of BCR on advanced heart dysfunction cases remains unclear but it seems that these patients still require a different approach maintaining a dismal prognosis. Overall survival and advanced cardiac disease Overall survival and advanced cardiac disease Figure 1 PFS for the whole AL group treated with BCR Figure 1. PFS for the whole AL group treated with BCR Disclosures Song: Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Onyx: Consultancy, Honoraria; BMS: Honoraria. Jimenez-Zepeda:Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria.

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