Authors: Palumbo et al. , EHA 2010 Abstract: 0566 Reviewed by: Dr. Tom Kouroukis

1. 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

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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 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

6. 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

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 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 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