2011多发性骨髓瘤进展CCOHematology2011MMSlidesCME.pptVIP

MM, multiple myeloma; MTD, maximum tolerated dose; PR, partial response; SD, stable disease; VGPR, very good partial response. ? Amitabha Mazumder, MD: Kumar and colleagues studied the weekly dosing schedule, delivering MLN9708 on Days 1, 8, and 15 of a 28-day cycle, which is similar to the weekly dosing schedule for bortezomib. However, with MLN9708, even heavily pretreated patients are receiving benefits with different and less severe toxicities. ? Kenneth Anderson, MD: We had the opportunity to do some of the preclinical testing on oral MLN9708, and it was well tolerated in our animal models and more active than bortezomib according to IC50 analyses, suggesting that it could have some activity in some of the bortezomib-resistant MM cell lines. It is also very exciting that proteasome-induced apoptosis was clearly visible in the myeloma cells of our xenograft mouse models, so observing similar results in the clinic is very gratifying. The results we are seeing with this very well tolerated oral agent reinforce my strong belief that oral combinations will become increasingly prominent in the list of treatment options for patients with MM. ? Sagar Lonial, MD: One of my relapsed patients is a striking example of how these results can change practice and outcomes. This patient had developed fairly significant bortezomib-induced neuropathy before enrolling in this trial, but has now achieved a PR, and, after receiving this regimen for almost 2 years, has favorable disease control and great quality of life with no reemergence of neuropathy. So, this demonstrates that we really are improving outcomes. * MM, multiple myeloma; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; RBC, red blood cell. ? Sagar Lonial, MD: These are data from a phase I/II study comparing pomalidomide alone with pomalidomide plus dexamethasone in patients with relapsed/refractory myeloma who were resistant to lenalidomide and bortezomib