OAB-034: Evaluating the impact of cytogenetic abnormalities on treatment outcomes in patients with AL amyloidosis: subanalyses from the ANDROMEDA study

Abstract

<h3>Background</h3> Amyloid light chain (AL) amyloidosis is a plasma cell disease characterized by the production of light chains that form amyloid fibril deposits in tissues leading to organ dysfunction and death. Cytogenetic abnormalities are common in patients (pts) with AL amyloidosis, and some are associated with poor outcomes. The ANDROMEDA study (NCT03201965) showed that addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone (D-VCd) was superior to VCd alone, with higher rates of hematologic complete response (CR) and an acceptable safety profile. Here, we explore outcomes in pts with cytogenetic abnormalities in ANDROMEDA. <h3>Methods</h3> Pts (N=388) with newly diagnosed AL amyloidosis were randomized 1:1 to D-VCd or VCd for 6 28-day cycles; thereafter, pts in the D-VCd group received daratumumab alone every 4 weeks for ≤24 total cycles. The proportion of pts with t(11;14), amp1q21, del13q14, and del17p13 based on fluorescence in situ hybridization and/or karyotyping was calculated. Overall (at any time during the study) hematologic CR rate and cardiac and renal response rates at 6 months were evaluated for each subgroup and summarized with descriptive statistics. Within each treatment group, hematologic response among pts with and without t(11;14) or amp1q21 was compared. <h3>Results</h3> 321 pts had testing (D-VCd, n=155; VCd, n=166). In the D-VCd and VCd groups, respectively, 42.9% vs 40.0% had t(11;14), 25.4% vs 20.3% had amp1q21, 16.2% vs 22.0% had del13q14, and 6.7% vs 6.1% had del17p13. At a median follow-up of 20.3 months, the hematologic CR rate was higher with D-VCd vs VCd across all 4 cytogenetic subgroups, ranging from 56–72% vs 0–14% (P<0.05 for all). Organ response rates were numerically higher with D-VCd in all subgroups, except for cardiac response rate in the del17p13 subgroup. In the VCd group, rates of hematologic CR and very good partial response or better (≥VGPR) were 12.5% vs 23.8% and 46.4% vs 56.0% in pts with (n=56) vs without (n=84) t(11;14) and 10.7% vs 19.1% and 53.6% vs 50.0% in pts with (n=28) and without (n=110) amp1q21. In the D-VCd group, rates of hematologic CR and ≥VGPR were 59.3% vs 61.1% and 77.8% vs 80.6% in pts with (n=54) vs without (n=72) t(11;14) and 59.4% vs 59.6% and 81.3% vs 80.9% in pts with (n=32) and without (n=94) amp1q21. <h3>Conclusion</h3> Consistent with the primary analysis of ANDROMEDA, subgroup analyses showed the benefit of D-VCd vs VCd, irrespective of cytogenetic abnormalities. Rates of deep hematologic response were not impacted by t(11;14) and amp1q21 in patients treated with D-VCd, but were generally lower in VCd-treated patients with t(11;14) and amp1q21. These findings further support the use of D-VCd as standard of care in pts with newly diagnosed AL amyloidosis, regardless of cytogenetic abnormalities.