Prognostic impact of rapid reduction of involved free light chains in multiple myeloma patients under first-line treatment with Bendamustine, Prednisone, and Bortezomib (BPV)

Abstract

Introduction Light chain involvement is observed in almost every patient (pt) with newly diagnosed multiple myeloma (MM). Owing to a relatively short half-life, rapid reduction in the involved free light chain (iFLC) is of potential prognostic value. Methods This retrospective analysis included 92 pts with newly diagnosed MM treated with bendamustine, prednisone, and bortezomib (BPV). Results After a median number of two (range 1–5) BPV cycles, the majority of pts (n = 86; 93%) responded with either sCR (n = 21), CR (n = 1), nCR (n = 25), VGPR (n = 20), or PR (n = 19). PFS and OS at 48 months were 39% and 67%, respectively. At baseline, 79 out of 92 pts (86%) had iFLC levels above the upper standard level and an abnormal ratio of involved to uninvolved free light chain ≥ 8. In a subgroup analysis of these pts, we evaluated the prognostic importance of an early reduction of the iFLC during the first two BPV cycles. A reduction ≥ 50% of the iFLC on day 8 of the first cycle was observed in 31 of 69 pts. These pts had a significantly better median PFS of 49 months as compared to 20 months in 38 pts with a lower iFLC reduction (p = 0.002). In contrast, OS did not differ significantly with a 48 months survival of 77% vs 69% (p > 0.05). Conclusion These results indicate that a rapid decrease in the iFLC on day 8 is an early prognostic marker for newly diagnosed MM pts undergoing BPV treatment.

Early free light chain reduction following treatment initiation predicts favorable outcome in intact immunoglobulin myeloma

“…Our data indicate that early assessment of sFLCs as early as cycle 1 has a significant impact on prognosis. Our results are also consistent with Holzhey et al who demonstrated that rapid sFLC decrease on day 8 is an early prognostic marker for newly diagnosed patients undergoing bortezomib-based treatments [ 10 ].…”

Bendamustine, prednisone and bortezomib (BPV) induction therapy prior autologous stem cell transplantation (ASCT) in 135 newly diagnosed multiple myeloma patients: comparison between patients with normal and impaired renal function

“…While the EuLITE study did not achieve any bene t in terms of dialysis independence, a French study using HCO-HD reported a signi cantly higher rate of hemodialysis independency after 6-12 months (Bridoux et al 2017; Hutchison et al 2019). Using induction therapy with BPV, our study group has also demonstrated a similarily rapid reduction in involved free light chain within the rst week of treatment in the majority of MM patients (Holzhey et al 2021). In the present study, we observed a favorable renal response rate of 61% after BPV induction, comparable to those observed for other regimes containing novel agents (Dimopoulos et al 2016).…”

Impact of the changing landscape of induction therapy prior to autologous stem cell transplantation in 540 newly diagnosed myeloma patients: a retrospective real-world study

“…The majority of patients with severe renal dysfunction or renal failure/dialysis received an induction treatment with BPV. As induction therapy, this combination has shown high efficacy and good tolerability in both transplant-eligible and non-transplant-eligible MM patients with renal impairment (Pönisch et al 2014 ; Poenisch et al 2015 ; Holzhey et al 2021 ). Specifically, this combination induced a rapid reduction in monoclonal LC production in the first few days of treatment, potentially preventing the development of irreversible renal failure (Pönisch et al 2015; Tessenow et al 2017 ; Holzhey et al 2021 ).…”

“…As induction therapy, this combination has shown high efficacy and good tolerability in both transplant-eligible and non-transplant-eligible MM patients with renal impairment (Pönisch et al 2014 ; Poenisch et al 2015 ; Holzhey et al 2021 ). Specifically, this combination induced a rapid reduction in monoclonal LC production in the first few days of treatment, potentially preventing the development of irreversible renal failure (Pönisch et al 2015; Tessenow et al 2017 ; Holzhey et al 2021 ). The German-Speaking Myeloma Multicenter Group (GMMG) previously reported that the bortezomib-based triplet therapy PAD before ASCT could overcome the negative prognostic impact of renal impairment (Scheid et al 2014 ).…”