Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone

Abstract

This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels o10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone.

Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

“…However, we did not find a significant impact of bortezomib resistance. In the report by Avet-Loiseau et al 27 although earlier bortezomib use was associated with inferior PFS and OS in univariate, was not significant in multivariate analysis. The authors suggested that the OS of patients who had progressed on thalidomide was affected negatively, only if they also had received previous bortezomib.…”

“…Indeed, our results in thalidomide-resistant patients are similar to that of thalidomideresistant patients treated in phase 2 or 3 trials. The median PFS of thalidomide refractory patients in MM009 and MM010 trials was 7 months (95% CI: 4.9-16.9), 26 the median PFS for thalidomide refractory patients in the report by Avet-Loiseau et al 27 was 5.7 months, whereas the median time to progression in immunomodulatory drug refractory patients in the MMY-3001 study was 6 months for patients treated with bortezomib and pegylated liposomal doxorubicin and 5.5 months for those treated with bortezomib alone. 28 It is also interesting that the addition of bortezomib to RD could not overcome the major detrimental effect of previous thalidomide resistance.…”

Treatment of relapsed and refractory multiple myeloma

“…25 Other studies of the impact of upfront bortezomib treatment on the outcome of relapse treatment with lenalidomide plus dexamethasone showed less favorable results. [26][27][28] Bortezomib retreatment has been investigated in a recent prospective Italian trial, where 40% of patients achieved a response with a TTP of 8 months and there was a better outcome in patients who achieved a complete response (CR) following prior bortezomib (see below). 29 …”

Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone

“…5,6 The presence of t(4;14) was also found to predict shorter survival in patients with advanced relapsed or refractory disease treated with lenalidomide and dexamethasone (9.4 versus 15.4 months; P=0.005). 7 The (4;14) translocation results in increased expression of the oncogenes fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma set domain (MMSET). [8][9][10] The chromosomal abnormality del(17p) is frequently associated with mutations in the TP53 gene or alterations in the p53 pathway.…”