Comparison of the current renal staging, progression and response criteria to predict renal survival in AL amyloidosis using a Mayo cohort

Abstract

Three sets of criteria (International Society of Amyloidosis [ISA], Palladini and Kastritis) were independently developed for staging, progression and response criteria to predict renal survival in patients with AL amyloidosis. We evaluated these criteria using a cohort of 495 newly diagnosed AL amyloidosis patients with renal involvement using time to event competing risk analysis at baseline, 3, 6 and 12 months after treatment. Only Palladini and Kastritis had a staging system and both predicted a higher risk of end stage renal disease (ESRD) in the stage III vs stage I patients but only the Palladini model was predictive for stage II patients. At 3 months, risk of ESRD was significantly higher for Palladini and ISA renal progression (hazard ratio [HR] 2.8 [95% CI: 1.5–5.3, p = .001] and 2.5 [CI: 1.4–4.6, p = .004, respectively]), but renal response was not significantly protective; conversely, the risk of ESRD was not significantly higher for the Kastritis renal progression, but was significantly protective for the Kastritis renal responders (HR 0.38 [95% CI: 0.17–0.84], p = .017). Both progression and response with ISA, Palladini and Kastritis criteria were predictive of ESRD at 6 months and 12 months. While the Palladini staging criteria at baseline, and the ISA and Palladini criteria for progression at 3 months performed better than the Kastritis criteria at baseline and 3 months post‐treatment, the Kastritis criteria performed better for response 3 months after treatment. All three sets of criteria performed well at and after 6 months post‐treatment. These differences are important when choosing endpoints for clinical trials.

The characteristics of patients with kidney light chain deposition disease concurrent with light chain amyloidosis

“…LCDD+AL appears to be associated with high tumor burden in most patients, as the underling hematologic condition was symptomatic MM in two-thirds of patients (including half of those without LCCN), in contrast to pure renal AL or LCDD in which >80% of patients have MGRS rather than symptomatic MM. 1,8,21 The median dFLC and % of bone marrow monoclonal plasma cells in LCDD+AL without LCCN were 137 mg/dl and 18%, respectively, which are higher than those reported in pure renal AL (8-15 mg/dl, 6%) 20,22 but comparable to pure renal LCDD (80-148 mg/dl, 10%) 8,23 . Noticeably, no LCDD+AL patient J o u r n a l P r e -p r o o f 10 had lymphoma or Waldenström's macroglobulinemia which are present in ≈5% of patients with pure LCDD 8 or AL.…”

“…LCDD+AL is very rare, accounting for 1% and 4% of our cases of AL and LCDD, respectively. Most patients were elderly at diagnosis, similar to those with pure renal AL 20 or LCDD 8 . The majority presented with NRP, severe kidney impairment, and microhematuria.…”

“…Other notable differences between our patients with LCDD+AL (without LCCN) and previously reported patients with pure AL or pure LCDD include higher frequency of females and microhematuria, lower frequency of other organ involvement (compared to AL), lower frequency of nodular glomerulosclerosis (compared to LCDD), and higher incidence of vascular-restricted AL deposits (compared to AL)(Table 4). 8,20,23,24,[26][27][28][29] Pathologically, LCDD+AL was more likely to be associated with λ than κ LC (λ:κ≈3:2).…”

Monitoring Patients with Light Chain (AL) Amyloidosis during and after Therapy: Response Assessment and Identification of Relapse

“…In order to avoid coding a reduction of proteinuria related to a worsening of kidney function as a response, renal response was defined as evaluable only in patients who did not reach a decrease in estimated glomerular filtration rate > 25% (defined as renal progression). This definition of renal response was subsequently validated in two different datasets reported by Kastritis et al [56] and Drosou et al [57]. Kastritis and colleagues also proposed a modification of the renal response criteria based on the reduction in the ratio of 24 h proteinuria to eGFR (24 h UPr/eGFR) by at least 25% or below 100 (if initially > 100), and this criterion was also tested in the Mayo cohort [57].…”

Biomarkers in AL Amyloidosis

“…This staging system could further separate patients at intermediate risk per the Palladini system, providing additional prognostic information. The two staging systems have been compared in an independent cohort, revealing their limitations [27].…”