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)

1
A phase 3 study to determine the efficacy and
safety of lenalidomide combined with melphalan
and prednisone in patients gt 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

2
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.
3
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
4
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
5
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 20099145-150)
• This study compares lenalidomide when used with
  melphalan and prednisone and when used in
  maintenance therapy

Palumbo et al., EHA 2010, abstract 0566
6
MPR-R vs MPR vs MP

• 459 patients, age gt 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
7
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
8
MPR-R vs MPR vs MP

• 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

MRP-R MRP MP P value
ORR (CRVGPRPR) 77 67 49 lt0.001
gtVGPR PR 32 45 33 34 12 37 lt0.001 -
Time to first response, median (months) 1.9 1.9 2.8 lt0.001
PFS, median, months Not reached 13.2 13 lt0.001
Palumbo et al., EHA 2010, abstract 0566
9
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
10
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 dont 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