authors: palumbo et al. , eha 2010 abstract: 0566 reviewed by: dr. tom kouroukis

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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


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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


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



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



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)



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



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



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



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


authors: palumbo et al. , eha 2010 abstract: 0566 reviewed by: dr. tom kouroukis

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