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

Abstract

We prospectively studied the impact of several cytogenetic abnormalities (CAs) in patients with relapsed/refractory myeloma who received lenalidomide and dexamethasone (RD) with or without the addition of bortezomib (V). On the basis of the presence of previous neuropathy, 50 patients were treated with RD and 49, without preexisting neuropathy, with VRD. The overall response rate was 63%, similar for RD and VRD. Poor risk cytogenetics were associated with lower response rates in RD (P ¼ 0.01), but not in VRD (P ¼ 0.219). The median progression-free survival (PFS) was similar for RD (9 months) and VRD (7 months). The median overall survival (OS) for all patients was 16 months, with no differences between RD or VRD regimens. Poor risk cytogenetics, especially del17p, resistance to previous thalidomide, elevated lactate dehydrogenase (LDH) and presence of extramedullary disease were associated with inferior response to therapy and shorter PFS and OS. The impact of other CAs on OS was more pronounced in RD. In conclusion, the presence of CAs is an important adverse prognostic factor for patients with relapsed/refractory myeloma, but resistance to previous thalidomide, elevated LDH and presence of extramedullary disease remain of major prognostic importance. The outcome of patients with del17p remains extremely poor even with VRD combination.

A question of class: Treatment options for patients with relapsed and/or refractory multiple myeloma

“…Until recently, risk classification did not impact on treatment decisions. However, data show that, compared with two-drug combinations, three-drug combinations improve outcomes for patients with high-risk cytogenetic abnormalities (CAs) (Stewart et al, 2015;Moreau et al, 2016a;Lonial et al, 2015a;Dimopoulos et al, 2010). For patients with high-risk CAs, aggressive therapy should be used to prevent the emergence of resistant clones.…”

“…A prospective study assessing the impact of cytogenetics on treatment outcome with bortezomib in combination with lenalidomide and dexamethasone found that for patients receiving bortezomib, there was no difference in ORR between those with high-risk CAs and those with standard-risk cytogenetics (P = 0.219) (Dimopoulos et al, 2010). However, in the control group (lenalidomide plus dexamethasone), the ORR was significantly lower for patients with highrisk CAs than for those with standard-risk cytogenetics (P = 0.01) (Dimopoulos et al, 2010).…”

Downregulation of MicroRNA-152 contributes to high expression of DKK1 in multiple myeloma

“…According to a previous study, 24 4 miRNAs, miR-152, miR15a, miR34a, and miR-223 were found to be downregulated (False discovery rate, FDR < 0.05) in the MM group compared to the non-MM group using a miRNA array. To validate this finding in our set of experiments, we performed qRT-PCR to detect the change of expression of these 4 microRNAs in B cells from 16 healthy donors and 18 primary human multiple myeloma samples.…”

“…2 There are several combinations of drugs such as melphalan, prednisone, bortezomib, lenalidomide, dexamethasone and thalidomide that are available as front line agents for MM. [3][4][5] Only few patients are eligible for chemotherapy followed by stem-cell transplantation. 6 Often, high-dose therapies are associated with fatal complications and relapse of MM.…”

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique

“…25 The value of stem cell transplant for chronic lymphatic leukemia is well documented. 26,27 Waldenströ m macroglobulinemia lacks the typical adverse cytogenetics 28 that are associated with diseases in which autologous stem cell transplant is regularly contemplated such as multiple myeloma. At diagnosis, À17p deletion is distinctly uncommon.…”