S875 Subcutaneous Daratumumab + Cyclophosphamide, Bortezomib, and Dexamethasone (Cybord) in Patients With Newly Diagnosed Amyloid Light Chain (Al) Amyloidosis: Updated Safety Run‐in Results of Andromeda

Comenzo, Ray; Kastritis, Eftathios; Maurer, Mathew S.; Zonder, Jeff; Minnema, Monique C.; Wechalekar, AD; Palladini, G.; Qin, Xiaoqi; Vasey, Sandra Y.; Aschan, J; Vermeulen, Jessica; Merlini, Giampaolo

doi:10.1097/01.hs9.0000561780.07253.e5

Cited by 9 publications

(6 citation statements)

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“…In a run-in cohort of 28 patients treated with CyBorD-Daratumumab, the overall haematological response rate was 96% (54% CR). At a median follow-up of 341 days, all patients in CR continued to respond to treatment 73 . This regimen used subcutaneous Daratumumab and grade 1 infusion related reactions were seen in 2 patients only.…”

Section: Daratumumab -A Transformative Role In Al Amyloidosismentioning

confidence: 98%

Systemic amyloidosis: moving into the spotlight

Cohen

Wechalekar

2020

Leukemia

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Systemic amyloidosis is a rare but increasingly recognised disease that is heterogeneous in presentation. Early diagnosis, whilst imperative, remains challenging but can improve prognosis and limit organ dysfunction. An increased repertoire of diagnostic imaging and histological techniques are becoming mainstream and promise to aid early diagnosis. Better risk stratification, via biomarkers and cytogenetics, has improved multidisciplinary treatment decisions. The use of novel agents has improved treatment efficacy, which translates into survival benefit. Newer strategies targeting predeposited amyloidogenic protein are under investigation. The current paper reviews available data relating to the most recent advances in the field of systemic amyloidosis.

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Section: Daratumumab -A Transformative Role In Al Amyloidosismentioning

confidence: 98%

Systemic amyloidosis: moving into the spotlight

Cohen

Wechalekar

2020

Leukemia

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“…Notable side effects included a low rate (7%) of grade 1-2 administration-related reactions with the use of subcutaneous daratumumab as well as slightly higher rates of pneumonia (8 vs 4%), lymphocytopenia (13 vs 10%), and diarrhea (6 vs 4%) with the addition of daratumumab. Still, despite the significant improvement in response parameters and overall tolerability with the addition of daratumumab to the CyBorD backbone, patient deaths were relatively equal between the two arms (27 patients in the Dara-CyBorD arm and 29 patients in the CyBorD arm) (18). Additional questions remain about the specific outcomes of the subgroup of patients with stage IIIA cardiac AL, as well as to the generalizability to patients with Stage IIIB disease.…”

Section: Daratumumab Emerges As a Treatmentmentioning

confidence: 98%

“…The randomized prospective ANDROMEDA study (NCT03201965) aims to show the potential improvement in hematologic response rates with the addition of subcutaneous daratumumab to CyBord and how this will translate to meaningful improvement in long term patient outcomes in the newly diagnosed AL setting. Of note patients with NT-proBNP greater than 8,500 ng/L were not eligible for ANDROMEDA, though 71% of patients had cardiac involvement with 37% of all patients having stage III disease (18,19). Primary results from ANDROMEDA have as of now been reported at the 2020 EHA meeting.…”

Section: Daratumumab Emerges As a Treatmentmentioning

confidence: 99%

Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis

Kaufman

Cerchione

2021

Front. Oncol.

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Therapy for light chain amyloidosis (AL) continues to evolve, and a new standard of care for the disease is rapidly forming. The risk of early death however, mainly from cardiac complications, remains an important benchmark yet to be definitively improved upon. This brief review explores recent advances in plasma cell directed therapy for AL, highlighting unique factors specific to these patients and AL biology driving differences in treatment strategies and clinical development compared with multiple myeloma. Improving upon proteasome inhibitor based upfront therapy combinations with the addition of anti-CD38 antibodies has shown promise with improved response rates in the ANDROMEDA (NCT03201965) study. Though depth and kinetics of achieving deep hematologic response as well as rates of biomarker defined organ response were improved with the addition of daratumumab to the combination of bortezomib, cyclophosphamide, and dexamethasone, death rates in each arm remained similar. Evaluation of other targeted and novel therapies in AL is ongoing, and we highlight efforts evaluating B-cell maturation antigen (BCMA) directed therapy, BCL-2 family inhibitors, and other novel agents in the field. We also look ahead to efforts to reimagine the clinical development of anti-fibrillar therapies after late phase study failures. Upcoming anti-amyloid fibril antibody studies explore opportunities to improve outcomes for the sickest AL patients with advanced cardiac disease, focusing on improving overall patient survival and reducing the risk of early death in this uniquely frail population.

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“…Most common AEs were diarrhoea, fatigue and peripheral oedema. IRR was developed by as little as 7% of patients (Comenzo et al , ).…”

Section: Monoclonal Antibodies Targetting Plasma Cell Clonementioning

confidence: 99%

Monoclonal antibodies in the treatment of AL amyloidosis: co‐targetting the plasma cell clone and amyloid deposits

Popková

Jelı́nek

2020

Br J Haematol

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Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a rare disease in which a small plasma cell clone produces toxic misfolded proteins that deposit in organs and impair their function. Currently, the only available treatment approach is the elimination of clonal plasma cells. However, a rapid strike that halts and possibly reverses organ damage is crucial. The development of agents that facilitate the clearance of pathological fibrillar deposits, therefore reducing the frailty of patients, is the needed supplement to plasma celldirected therapy. Monoclonal antibodies provide therapy against malignant plasma cells (daratumumab, isatuximab, elotuzumab) but they are also able to target and eliminate the amyloid from organs (NEOD001, CAEL-101, dezamizumab). From the plasma cell-directed group, daratumumab in monotherapy has proved to be extremely efficient in relapsed AL amyloidosis, exceeding its results in multiple myeloma. Compared to other agents, monoclonal antibodies possess the advantage of high selectivity and low toxicity and could potentially become future game-changers in this field. Co-targetting of the plasma cell clone and amyloid deposits shall together be translated in the revolutionary improved outcome of potentially curable AL amyloidosis.

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S875 Subcutaneous Daratumumab + Cyclophosphamide, Bortezomib, and Dexamethasone (Cybord) in Patients With Newly Diagnosed Amyloid Light Chain (Al) Amyloidosis: Updated Safety Run‐in Results of Andromeda

Cited by 9 publications

References 0 publications

Systemic amyloidosis: moving into the spotlight

Systemic amyloidosis: moving into the spotlight

Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis

Monoclonal antibodies in the treatment of AL amyloidosis: co‐targetting the plasma cell clone and amyloid deposits

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