Extending autologous transplantation as first line therapy in multiple myeloma patients with severe renal impairment: a retrospective study by the SFGM-TC

Abstract

Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m melphalan is a beneficial procedure for MM patients with renal failure.

Autologous peripheral blood stem cell transplantation in dialysis‐dependent multiple myeloma patients—DAUTOS Study of the Polish Myeloma Study Group

“…Similar results can be found in the paper by Raab et al where PFS were 2 and 1 years (there are not comments concerning this finding or hypothesis about its sources), and OS were 3 years and 4.4 years in DD and NRF patients, respectively . The medians of PFS reported in other papers in DD patients were 1.7 year, 2 years, 1.9 years, 1.8 years and 4.3 years . These results are similar to our PFS (3.3 years, Figure A) especially when we take into account the 95% confidence limit.…”

“…Our results support these points of view since 5‐year OS and medians of OS were similar in DD and NRF patients (39% vs 50%, P < .45; 3.3 vs 5.1 years, P < .45). In other papers, medians of OS in DD patients were 3 years, 3.8 years, 3.4 years and 6.3 years frequency of toxicity in DD patients (Table , Figure B).…”

“…In other papers, medians of OS in DD patients were 3 years, 3.8 years, 3.4 years and 6.3 years frequency of toxicity in DD patients (Table , Figure B). This finding consistent on non‐inferiority of OS in DD patients has been supported even in subgroups of patients selected on the basis of toxicity experience after auto‐PBSCT ie mucositis, parenteral nutrition, diarrhoea, infection including neutropenic fever, PLT and RBC transfusion (Figure B).…”

“…If we assume that altered pharmacokinetics of melphalan especially in DD patients may result in a higher concentration of the drug, this might explain the higher level of clinical toxicity of grade≥3 observed in these patients compared to NRF patients (Table ), ie mucositis (50% vs 22%, P < .017), parenteral nutrition as a consequence of mucositis (50% vs 24%, P < .034), diarrhoea (25% vs 16%, P < .37), other gastrointestinal complications (4% vs 2%, P < .52) and infections including neutropenic fever (79% vs 49%, P < .014). Mucositis of grade≥3 incidence in DD patients after auto‐PBSCT in other papers were 67%, 49%, and 29% . It is known that mucositis and neutropenia are only 2 of many risk factors predisposing to an increased risk of infection after auto‐PBSCT.…”

“…There are retrospective, inconsistent studies devoted to the safety and efficacy of auto-PBSCT procedure in DD patients. 4,[7][8][9][10][11][12][13] We aimed to provide characteristics of DD patients and to evaluate the outcomes of high dose therapy followed by auto-PBSCT in a real-life scenario of observational study and after propensity score matching with normal renal function MM patients (NRF).…”