Emerging therapy in light-chain and acquired transthyretin-related amyloidosis: an Italian single-centre experience in heart transplantation

Abstract

Aims The prognosis for patients affected by light-chain cardiac amyloidosis and acquired transthyretin-related (TTR) amyloidosis is poor. Heart transplantation (HTx) could improve prognosis also enabling autologous stem cell transplantation (ASCT) in the first group. Methods and results A total of 36 patients affected by systemic amyloidosis have been referred to our centre from 2009 to 2019. Of these, nine had cardiac involvement: seven by light-chain amyloidosis and two by acquired TTR amyloidosis. None died while waiting for HTx. A specific internal protocol useful to select candidates and to monitor the organ involvement after HTx was developed. Median age at diagnosis was 54 years and 66% were male. The most common short-term complication after HTx was renal failure (44%), followed by acute cardiac rejection more than 2R (22%). ASCT was performed in six out of seven light-chain cardiac amyloidosis patients, with a median time of 6 months after HTx. Two patients affected by light-chain cardiac amyloidosis died due to amyloidosis relapse: one before undergoing ASCT. After a median follow-up of 31 (7–124) months, 1- and 5-year survival was 88 and 66% in the cardiac light-chain amyloidosis group. Conversely, 1- and 5-year survival was 100% in the acquired TTR amyloidosis group. Conclusion HTx may represent a valuable option in carefully selected patients. ASCT after HTx is an effective treatment that could decrease amyloidosis relapse in light-chain cardiac amyloidosis patients. A multidisciplinary approach is mandatory to select the best candidates and to obtain the most effective results with a specific surveillance follow-up protocol.

Light-chain cardiac amyloidosis: a case report of extraordinary sustained pathological response to cyclophosphamide, bortezomib, and dexamethasone combined therapy

“…In recent transplant series, some patients did not have time to receive ASCT after HTx due to AL amyloidosis progression. 16 Therefore, this treatment option is feasible in well-selected AL-CA patients without clinically significant extra-cardiac amyloid where ASCT is expected to confer substantial survival benefit and can be performed with relatively little risk for treatment-related mortality. 17 …”

Molecular Determinants Underlying the Anti-Cancer Efficacy of CD38 Monoclonal Antibodies in Hematological Malignancies

“…In contrast to MM, the clonal plasma cell in amyloidosis (AL) has a lower proliferation index [ 45 ]. Despite this, AL clonal plasma cells express surface CD38 [ 46 ], allowing monoclonal antibodies, such as daratumumab, to inhibit light-chain production [ 47 , 48 ]. A considerable amount of malignant clone of plasma cells in Waldenström macroglobulinemia patients expresses CD38 (40–70%) [ 49 , 50 , 51 ], explaining the rationale for a recently completed clinical trial to treat Waldenström macroglobulinemia patients with daratumumab [ 52 ].…”

Heart transplantation in cardiac amyloidosis

“…Lacyet al [27] from the Mayo Clinic published a series of 11 patients undergoing sequential HTx/ASCT, reporting that 2/11 patients died from transplant-related toxicity and 3/11 died from progressive amyloidosis. The largest series of patients transplanted for CA was published in June 2021 from the United Network for Organ Sharing registry from 1987 to 2018, where the authors reported 313 patients affected by CA who underwent isolated HTx, with encouraging results [28] .…”