The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment

Abstract

Key Points• The monotypic and polytypic PC compartments assessed by MFC are prognostic in AL amyloidosis.• MFC may play a role in the definition of hematologic response to treatment.Multiparametric flow cytometry (MFC) in amyloid light-chain (AL) amyloidosis has not been widely adopted and, consequently, there is little information on its clinical relevance. We studied 173 patients with AL amyloidosis who underwent MFC immunophenotyping of bone marrow sample at diagnosis and 82 patients at the end of the first line of treatment (EOT). The number of monotypic plasma cells (PCs) and the polytypic PCs/bone marrow PCs (pPCs/BMPCs) ratio were analyzed. At diagnosis, ‡2.5% monotypic PCs was associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with patients with <2.5% monotypic PCs (2-year PFS 41% vs 56%, P 5 .007; 2-year OS 55% vs 70%; P 5 .01). Additionally, patients with a pPCs/BMPCs ratio of £5% had a shorter PFS compared with patients with pPCs/BMPCs ratio >5% (2-year PFS 43% vs 55%; P 5 .02), but without OS difference (2-year OS 60% vs 67%; P 5 .19). In a multivariate analysis, the monotypic PCs retained an independent prediction for PFS/OS, whereas the pPCs/BMPCs ratio retained significance only for PFS. At EOT, ‡0.1% monotypic PCs was associated with a shorter PFS and OS compared with patients with <0.1% monotypic PCs (2-year PFS 31% vs 87%; P < .0001; 2-year OS 87% vs 98%, P 5 .02). In a subgroup analysis among patients who attained a very good partial response or better, the monotypic PCs at the 0.1% cutoff was predictive for progression rate but not for PFS/OS. MFC is prognostic for AL amyloidosis at diagnosis and at EOT. MFC may have a role in the definition of hematologic response. (Blood. 2017;129(1):82-87)

Assessment of minimal residual disease using multiparametric flow cytometry in patients with AL amyloidosis

“…The clinical relevance of flow cytometry-based MRD assessment and its predictive value on organ response in AL amyloidosis is of growing interest. [6][7][8][9][10] Organ response is a crucial outcome for patients with this disease, yet the precise mechanisms of organ dysfunction and how hematologic response following treatment affects organ recovery are not well understood. Generally, a deep hematologic response (hemVGPR or better) is required for organ response, but even those who achieve hemCR can endure persistent organ dysfunction.…”

“…In AL amyloidosis, an MFC method using surface markers adopted from multiple myeloma was shown to detect aberrant PCs at the time of diagnosis with high sensitivity and the presence of ,0.1% monotypic PCs by MFC after initial treatment to predict longer survival. 6,7 Subsequent studies indicated longer progression-free survival and possibly improved organ response with MRD negativity. [8][9][10] With small sample sizes in these previous investigations, we sought to elucidate the clinical relevance of MFC-based MRD assessment in patients with hemCR.…”

Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis

“…A rapid reduction of light chains to very low levels with treatment results in organ improvement and better survival . We have previously demonstrated that lack of residual bone marrow monotypic plasma cells using flow cytometry (sensitivity ≥1 × 10 −4 ) is associated with superior outcomes . There is limited data on outcomes in AL amyloidosis using next generation MRD assessment methods (next generation flow cytometry [NGF] or next generation sequencing [NGS]), which are currently endorsed for MRD response evaluation for multiple myeloma by the International Myeloma Working Group .…”

Blood mass spectrometry detects residual disease better than standard techniques in light-chain amyloidosis

“…MS detected residual disease among AL amyloidosis patients in hematologic CR, not only in the context of negative blood and urine IFE and serum FLC but also in the context of a negative bone marrow employing sixcolor flow cytometry, which has approximately one order of magnitude less sensitivity than the next-generation flow cytometry and two orders of magnitude than the next-generation sequencing. Current consensus response criteria exclude bone marrow as part of hematologic response 6,7 , but we included bone marrow response because emerging data demonstrate that patients with a negative bone marrow by flow cytometry fare better than those without [13][14][15][16][17][18] . Despite the limited sample size, there was a very significant difference in progression-free survival between the MS-positive and -negative patients.…”