Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival

Abstract

Standard myeloma treatment response criteria are determined principally by changes in the monoclonal protein. Reduction in the size of the proliferative component of malignant plasma cells may be an additional metric of assessing response to therapy. We retrospectively analyzed 176 patients with newly diagnosed myeloma with a measurable plasma cell labeling index (PCLI) at diagnosis and repeat measurement 4 months after initiation of therapy. PCLI response was defined as a > 60% reduction. Baseline PCLI is an independent prognostic factor; therefore, we categorized patients into 3 groups: PCLI > 3% (high), > 1% (intermediate), and < 1% (low). Patients achieving a greater PCLI response had improved median overall survival of 54 months compared with 29 months in nonresponders (P ‫؍‬ .02). Improved median overall survival with PCLI response occurred in the high initial PCLI group (28 vs 7 months; P ‫؍‬ .003) and intermediate group (64 vs 24 months; P ‫؍‬ .002). The application of PCLI response and serum M-spike response together provided further prognostic information. On multivariate analysis, the prognostic value of PCLI response was independent of ␤ 2 -microglobulin, elevated creatinine, serum M-spike response, and baseline PCLI. We conclude that a significant reduction in plasma cell proliferation in patients with newly diagnosed myeloma is an important predictor of survival. (Blood. 2011; 118(10):2702-2707)

BrdU incorporation in multiparameter flow cytometry: A new cell cycle assessment approach in multiple myeloma

“…This underlines the need of useful biological and prognostic information's to develop rational and targeted therapies. The plasma cell labeling index was shown to be one of the most powerful risk factor in MM (10,11). However, this approach did not separate malignant MM cells from normal PC.…”

“…Proliferating PC, that is, the growing fraction of MM cells, have been evaluated by flow cytometry detection of newly synthesized DNA using techniques based on the uptake of tritiated thymidine or bromodeoxyuridine (BrdU) . The so‐called plasma cell labeling index (PCLI) based on propidium iodide incorporation has been shown to be a powerful and independent predictor of survival in MM as the assessment of Ki‐67 expressing cells in the malignant fraction . Although proliferation markers have been studied in MM, none of the current prognostic scores or staging systems, available to physicians nowadays, include these markers.…”

Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of multiple myeloma: initial clinical efficiency results

“…Because of the heterogeneity of multiple myeloma [24], one single clinical index is unlikely to be able to differentiate between all tumour statuses, which supports the utility of different myeloma indices. We selected β 2 m and albumin for discriminant analysis, as these biochemical parameters are simple, easily available and inexpensive parameters that can be used as prognostic markers [25][26][27][28]. β2m is released into serum, with elevated levels in several lymphoproliferative disorders, including multiple myeloma.…”

Risk and Response-Adapted Treatment in Multiple Myeloma

“…Given that autologous stem cell transplantation (ASCT) is the most appropriate therapeutic choice for eligible patients, the role of tandem ASCT or alloSCT is still debated [16]. Other prognostic features related to the malignant clone are the proliferation index (PI) [17] and the plasmablastic morphology [18], both associated with frequent adverse cytogenetic lesions.…”

“…Apart from cytogenetic and molecular abnormalities, some clinical presentations observed at relapse, such as secondary plasma cell leukemia and extramedullary localizations, may benefit from certain specifically oriented strategies. Some authors have suggested adapting treatment in patients displaying a plasmablastic morphology and a high PI using anti-proliferative drugs, such as anthracyclines and inhibitors of aurora kinase [17,94].…”