Targeted therapeutics for multiple myeloma: The arrival of a risk-stratified approach

Abstract

Multiple myeloma (MM) remains an incurable hematologic malignancy characterized by frequent early responses, inevitably followed by treatment relapse.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials

“…22 The majority of the patients with t(4;14) have an estimated median survival after diagnosis of 18-36 months despite tandem HDT, and among this population new innovative approaches are clearly needed. 21 On the contrary, and that is the major finding of this study, we have identified a subgroup of approximately 45% of the patients with both b 2 -microglobulin o4 mg/l and Hb level X10 g/dl at diagnosis which is experiencing prolonged survival after tandem transplant and benefits from HDT. The median EFS in this subgroup of patients was 27 months, strictly identical to the EFS observed in the intensive arm (single ASCT) of the French IFM90 trial, 23 of the British MRC VII trial 24 or the Italian MMSG97 trial.…”

“…[11][12][13][14][15]20 Some authors even suggest that these patients receive minimal benefit from ASCT and could be candidates for novel therapeutic approaches. 12,13,21 Our study, the largest one for patients with t(4;14) treated with upfront HDT, allows several comments. The overall response Heterogeneity of t(4;14) in multiple myeloma P Moreau et al rates after both induction and HDT were identical in this subgroup of patients to those achieved in patients without t (4;14) indicating that primary drug resistance may not be the main cause of disease severity.…”

“…New targeted therapies such as FGFR3 inhibitor currently evaluated in prospective protocols could also improve the outcome of this aggressive disease in patients expressing FGFR3. 21,28 46 vs 300 pts Heterogeneity of t(4;14) in multiple myeloma P Moreau et al…”

Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma

“…The use of thalidomide and bortezomib has improved response rates and response duration in MM patients [13][14][15][16][17][18][19][20]. High-dose chemotherapy with stem cell transplantation can enhance the rate of complete remission and prolong the survival of patients.…”

Molecular mechanisms of nutlin-induced apoptosis in multiple myeloma

“…1,2 MM is incurable with current therapies and potential therapeutic targets for new drug development is clinically important. 3 We and others have shown that mutations/deletions of p53, a tumor suppressor protein, are relatively rare in MM.…”