authors: palumbo et al. , eha 2010 abstract: 0566 reviewed by: dr. tom kouroukis
DESCRIPTION
A phase 3 study to determine the efficacy and safety of lenalidomide combined with melphalan and prednisone in patients > 65 years with newly diagnosed multiple myeloma (NDMM). Authors: Palumbo et al. , EHA 2010 Abstract: 0566 Reviewed by: Dr. Tom Kouroukis Date posted: Jul 2 2010. - PowerPoint PPT PresentationTRANSCRIPT
www.OncologyEducation.ca
A phase 3 study to determine the efficacy and safety of lenalidomide combined with
melphalan and prednisone in patients > 65 years with newly diagnosed multiple myeloma
(NDMM)
Authors: Palumbo et al., EHA 2010Abstract: 0566Reviewed by: Dr. Tom KouroukisDate posted: Jul 2 2010
www.OncologyEducation.ca
Thank you for downloading this update. Please feel free to use it for educational purposes.
Please acknowledge OncologyEducation.ca and Dr. Kouroukis when using these slides.
www.OncologyEducation.ca
Background
• Older patients with myeloma experience greater toxicity with high dose melphalan and stem cell transplantation and are therefore treated with non-transplant based regimens
• Traditionally melphalan and prednisone based therapy was standard, but the addition of new agents has changed to a new standard
• Studies have shown benefits to adding thalidomide to melphalan and prednisone (MPT), but thalidomide is difficult to obtain and not yet Health Canada approved
Palumbo et al., EHA 2010, abstract 0566
www.OncologyEducation.ca
Background
• The addition of bortezomib to melphalan and prednisone (VMP) has shown benefits over MP in older patients with newly diagnosed myeloma (VISTA study, San Miguel et al., NEJM 2008)
• VMP is approved for upfront therapy in non-transplant patients and is reimbursed
• Lenalidomide is a potent immunomodulatory agent that has significant activity in both newly diagnosed and relapsed myeloma patients
Palumbo et al., EHA 2010, abstract 0566
www.OncologyEducation.ca
Background
• Lenalidomide combinations with melphalan and prednisone has thus been tested
• Original reports by Palumbo MPR have shown good response rates but with myelotoxicity (Clin Lymph Myeloma 2009:9:145-150)
• This study compares lenalidomide when used with melphalan and prednisone and when used in maintenance therapy
Palumbo et al., EHA 2010, abstract 0566
www.OncologyEducation.ca
MPR-R vs MPR vs MP
• 459 patients, age > 65 yrs, newly diagnosed multiple myeloma
• Randomized to:– Melphalan, prednisone, lenalidomide with
lenalidomide maintenance (MPR-R)– Melphalan, prednisone, lenalidomide with placebo
maintenance (MPR)– Melphalan, prednisone with placebo maintenance
(MP)
Palumbo et al., EHA 2010, abstract 0566
www.OncologyEducation.ca
MPR-R vs MPR vs MP
• Melphalan was given at 0.18 mg/kg/day on days 1-4; prednisone 2 mg/kg/day on days 1-4; lenalidomide 10 mg/day on days 1-21; cycles given every 28 days
• After 9 cycles of therapy with MPR or MP; lenalidomide was dosed 10 mg/day or placebo until progression
• Primary comparison was between MPR-R vs MP for PFS
• This represents a pre-planned interim analysis after 50% of events
Palumbo et al., EHA 2010, abstract 0566
www.OncologyEducation.ca
MPR-R vs MPR vs MP
MRP-R MRP MP P value
ORR (CR+VGPR+PR)
77% 67% 49% <0.001
>VGPRPR
32%45%
33%34%
12%37%
<0.001-
Time to first response, median (months)
1.9 1.9 2.8 <0.001
PFS, median, months
Not reached 13.2 13 <0.001
• P values are for the comparison of MPR-R vs MP• MPR-R resulted in higher response rates, more rapid responses and longer PFS compared with MP
Palumbo et al., EHA 2010, abstract 0566
www.OncologyEducation.ca
MPR-R vs MPR vs MP
• Secondary analysis showed that lenalidomide maintenance extended PFS in patients treated with MPR
• 16% of patients discontinued MPR-R due to adverse events
• 70% of patients on MPR-R experienced grade 3/4 neutropenia compared with 29% with MP; FN rates not completely reported
Palumbo et al., EHA 2010, abstract 0566
www.OncologyEducation.ca
BOTTOM-LINE FOR CANADIAN MEDICAL ONCOLOGISTS
• MPR-R is a superior regimen compared with MP; albeit with more hematological toxicities
• Lenalidomide maintenance appears to add to PFS after treatment with MPR
• We don’t have data on the potential contribution of lenalidomide maintenance in patient who might be treated with MP alone
• No direct comparison to thalidomide based induction or maintenance regimens
• Median f/u is short at 9.4 months
Palumbo et al., EHA 2010, abstract 0566