Adding daratumumab to bortezomib-containing therapy improves outcomes for people with newly-diagnosed immunoglobulin light-chain (AL) amyloidosis, a new study has shown.
The CD38-targeted therapy increased haematologic complete response rates and survival free from major organ deterioration or haematologic progression in the international phase 3 ANDROMEDA trial, which included Australian centres.
The study compared haematologic responses in 388 patients taking bortezomib, cyclophosphamide and dexamethasone alone or with daratumumab.
At median follow-up of 11.4 months, 53% of daratumumab patients achieved haematologic complete response, versus 18% in the control group (RRR: 2.9, 95% CI: 2.1–4.1, P < 0.001).
A haematologic complete response — achieved in 60 days with daratumumab and 85 days in the control arm — was defined as “an involved free light-chain level less than the upper limit of normal range with negative serum and urine immunofixation”.
“Normalisation of the uninvolved free light-chain level or free light-chain ratio was not required to determine a complete response,” the study authors wrote in NEJM.
Very pleased and excited to see our hard work published in #NEJM – confirming daratumumab as the new standard of care for treatment of AL Amyloidosis @OzAmyloidosis #amyloidosis Already approved by the FDA, let’s hope it’s approved soon for Australian patients. pic.twitter.com/3MPAtzbYXl
— Dr Simon Gibbs (@simondjgibbs) July 1, 2021
Cardiac response was observed in 42% (n=118) of daratumumab patients at 6 months and 22% (n=117) in the control arm, while 3% and 8% progressed, respectively.
Renal responses were also better in the daratumumab group, with 53% (n=117) achieving a response at 6 months versus 24% in the control arm (n=113). Renal progression was observed in 4% and 11% of patients respectively.
Daratumumab patients had longer survival free from major organ deterioration or haematologic progression (hazard ratio for major organ deterioration, haematologic progression, or death: 0.58, 95% CI: 0.36–0.93, P = 0.02), with haematologic progression only occurring in 4% of daratumumab patients versus 13% of the control group.
The study authors commented that in addition to the higher frequency of a hematologic complete response, hematologic responses were deeper and occurred more rapidly in the daratumumab group. However, overall survival did not differ substantially between the two groups at the time of this primary analysis.
Daratumumab and bortezomib, cyclophosphamide and dexamethasone’s safety profiles were consistent with their known profiles and the underlying disease, they added.
“From a clinical standpoint, subcutaneous daratumumab provides important advantages for the population of patients with AL amyloidosis. These include reduced systemic administration-related reactions and negligible volume of administration,” the authors noted.
The FDA approved the daratumumab combination therapy for newly-diagnosed AL amyloidosis patients in January 2021. Study co-author, Dr Simon Gibbs, a consultant haematologist (Myeloma/Amyloidosis Lead) at the Department of Clinical Haematology Eastern Health (Melbourne), tweeted that he hoped it would be approved for Australian patients soon.