28.6. Guidelines for monitoring AL amyloidosis

Chapter 28

28.6.1. International Myeloma Working Group (2009)

In the guidelines for sFLC analysis in MM and related disorders (Section 25.3.1), the IMWG recommend sFLC assays for the quantitative monitoring of patients with oligosecretory plasma cell disorders, including patients with AL amyloidosis [167].

28.6.2. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis (2012)

In 2012, Comenzo et al. [23] published consensus guidelines for the definition of organ involvement and response to treatment in AL amyloidosis. The guidelines are based on data from an international cohort of 816 patients from seven referral centres, for which haematological responses were assessed 3 and/or 6 months after initiation of first-line therapy. Haematological response categories were defined, as detailed in Table 28.2. There was a strong correlation between the haematological response category at 3 or 6 months and overall survival (Section 28.7). The haematological response criteria were subsequently validated in a prospective study of 374 patients [117], and have now been widely adopted and incorporated into national guidelines [24][25].

Haematologic response category Definition
Complete response Normalisation of sFLC levels and ratio,
negative serum and urine immunofixation
Very good partial response A reduction in the dFLC to <40 mg/L
Partial response A >50% reduction in the dFLC
No response Less than a PR
Progression From CR:
any detectable monoclonal protein or abnormal FLC ratio
(light chain must double)
From PR:
50% increase in serum monoclonal protein to >5 g/L,
or 50% increase in urine monoclonal protein to >200 mg/day
(a visible peak must be present) or FLC increase of 50% to >100 mg/L

Table 28.2. Haematologic response and progression criteria [23].

The definition of measurable disease by sFLC analysis was defined as a dFLC of ≥50 mg/L, and covers approximately 85% of newly diagnosed AL amyloidosis patients. Two studies have compared the clinical characteristics and outcome of patients with non-evaluable (dFLC <50 mg/L) with those of patients with evaluable sFLCs at diagnosis [618][927]. Schonland et al. [618] concluded that patients with non-evaluable sFLCs represent as a distinct clincial entity with a small plasma cell clone, irrespective of cytogenetic results. Sidana et al. [927] added that these patients tend to have less cardiac and liver involvement, which may result from reduced FLC deposition. Both studies agreed that patients with non-evaluable FLCs at diagnosis tend to have a very favourable outcome. For example, Sidana et al. [927] reported a median survival of 8.3 years for patients with dFLC <50 mg/L, compared with only 2.4 years for patients with dFLC ≥50 mg/L. Therefore, the underrepresentation of non-evaluable patients in clinical trials and studies (because their haematologic response cannot be reliably measured) would be expected to adversely influence results [618].

28.6.3. British Committee for Standards in Haematology (2015)

The British Committee for Standards in Haematology guidelines on the management of AL amyloidosis [24] define haematological response criteria according to the international consensus guideline, described in Section 28.6.2 [23]. The guidelines recommend monitoring response to treatment with sFLCs or monoclonal protein measurements after each cycle of chemotherapy and every 1 - 3 months thereafter, with the aim of switching to an alternative regimen as soon as the current one is proving ineffectual, which may be assessed after three cycles of therapy or earlier in cardiac patients. The guidelines also recognise that Freelite sFLC assays are well established for monitoring response in AL amyloidosis, whilst FLC assays from other manufacturers have not been validated (Chapter 8).