Rafael Fonseca MD Chair, Department of Medicine Mayo Clinic in AZ What is the optimal therapeutic approach for MM patients with bor-len relapsed/refractory disease? Novel doublets ± corticosteroids Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida Mayo Clinic College of Medicine Mayo Clinic Comprehensive Cancer Center

Disclosures Consulting: AMGEN, Genzyme, BMS, Otsuka, Celgene, Medtronic, Lilly, Millennium, Binding Site, Onyx, Bayer Speakers Bureaus: None Research: Cylene, Proteolix Patent for FISH based prognostication in MM - about $1500 per year Registered independent Believe in stem cell transplant Dislike wasting your time with this slide

POM-V-D 1-4 lines of Rx (median 2) Refractory to lenalidomide (67% progressed as last Rx) Not to bortezomib >= 2 cycles bortezomib 28 pts enrolled, 20 evaluable for response Bortezomib d 1, 4, 8, &11 1 & 8 after cycle 8

POM-V-D MTD pomalidomide 4 mg and bortezomib 1.3 mg/m2 ORR is 75% 30% VGPR or better One sCR TTR is 1 month Need larger randomized trials

A Phase I/II Trial of Pomalidomide, Bortezomib and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma Joseph Mikhael MD1, Vivek Roy2, MD; Paul Richardson MD3; Andrzej Jakubowiak, MD4; Kristina Laumann5, Betsy LaPlant5; Angela Dispenzieri, MD5; S. Vincent Rajkumar, MD5; Rafael Fonseca, MD1; Nelson Leung, MD5; Francis K. Buadi, MD5, P. Leif Bergsagel; MD1, Robert A. Kyle, MD5; Thomas E. Witzig, MD5; Craig B. Reeder, MD; John A. Lust, MD, PhD5; Stephen J. Russell, MD, PhD5; Suzanne R. Hayman, MD5; Shaji Kumar, MD5; David Dingli, MD, PhD5; Stephen M. Ansell, MD, PhD5, Robert J. Dalton, MD5; Yi Lin, MD, PhD5, Taimur Sher, MD2, Prashant Kapoor, MD5, Arleigh McCurdy, MD5; Asher Chanan-Khan, MD2, A. Keith Stewart, MBCHB1; Morie A. Gertz, MD5, Martha Q. Lacy MD5

Results A total of 25 patients have been accrued to the trial: 9 in phase I (3 at dose level 1 and 6 at dose level 2) 16 additional at dose level 2 for 22 total in phase II.

Results Phase I For the 9 patients in Phase I: Response in Phase I: Median age was 63 33% were mSMART intermediate or high risk Median number of prior regimens was 3 All patients had been treated with steroids and lenalidomide 89% had received and autologous stem cell transplant Response in Phase I: 8/9 pts responded (5CR, 2 VGPR and 1 PR)

Results – Phase II For the 16 patients at dose level 2: median age was 66, 31% percent had mSMART defined high risk status Median prior lines of therapy was 3 (1-6), 100% treated with lenalidomide, 75% had stem cell transplant 50% had bortezomib 31% received thalidomide Response rate is 94%: 5 CR, 4 VGPR and 6 PR.

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Summary Combinatorial strategies probably best Unprecedented ability to induce response Good DOR Much more progress is needed!