1. Amitabha Mazumder, MD Professor of Medicine New York Medical College Attending Physician, Medical Oncology St. Vincent’s Comprehensive Cancer Center Relapsed/Refractory Multiple Myeloma: Options for Subsequent Therapy This program is supported by an educational grant from

2. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma About These Slides  Our thanks to the presenters who gave permission to include their original data  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Overview  Scenarios for Treatment of Relapsed/Refractory Myeloma  Lenalidomide-Containing Regimens  Bortezomib-Containing Regimens  New Aspects in Supportive Care  Clinical Trials

4. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma IMWG Response Criteria  Response (CR + PR) and disease progression unchanged if serum and urinary M-protein are measurable  New response criteria (vs EBMT/IBMTR criteria) –Addition of “stringent complete response” (sCR) and VGPR –Elimination of “minor” criteria; incorporation of serum-free light chain assay –“Clinical relapse” as optional endpoint –“Relapse from CR” only applicable to DFS; use progressive disease to calculate TTP and PFS in patients with CR Durie BG, et al. Leukemia. 2006;20:1467-1473.

5. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma IMWG Response Criteria  Practical details revised and clarified (vs EBMT/IBMTR criteria) –Eliminated need for consecutive confirmations 6 wks apart –Defined “start time” for response duration –Quantitative immunoglobulin levels allowed if M-protein unavailable or unreliable –Requirement of at least a PR for new drug trials Durie BG, et al. Leukemia. 2006;20:1467-1473.

6. Lenalidomide-Containing Regimens

7. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Lenalidomide + Dexamethasone: Recommendations for Patient Selection Baseline Factor(s)Recommendations  2 -M levels Cytogenetic factors Previous treatments Not exclusion criteria AgeNot exclusion criterion Monitoring of pts 65 yrs or older is recommended Fragile patients older than 75 yrs, dexamethasone dose may need to be reduced to avoid toxicity Renal impairmentNot exclusion criterion Care should be taken in dose selection; it would be prudent to monitor renal function Dose reductions might be needed when toxicity occurs Dimopoulos M, et al. EHA 2007. Abstract.

8. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma MM-009/010: Phase III Study Design Weber DM, et al. N Engl J Med. 2007;357:2133-2142. Pts with relapsed MM following ≥ 1 treatment (N = 353) Treatment continued until disease progression or unacceptable toxicity Lenalidomide 25 mg Days 1-21 Dexamethasone 40 mg PO Days 1-4 (and Days 9-12 and 17-20 for first 4 cycles) (n = 177) Placebo Days 1-21 Dexamethasone 40 mg PO Days 1-4 (and Days 9-12 and 17-20 for first 4 cycles) (n = 176) Day 28 Primary endpoint: time to disease progression Secondary endpoints: OS, response rate

9. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Len/Dex in Relapsed/Refractory MM and Renal Impairment: MM-009/MM-010 Weber DM, et al. ASCO 2008. Abstract 8542. Pts (%) Degree of Renal Impairment (CrCl mL/min) by Response Type P =.11* P =.06* P <.01* 33 14 17 27 22 13 26 12 21 12 31 6 70 60 50 40 30 20 10 0 None (≥ 80) Mild (≥ 50 to < 80) Moderate (≥ 30 to < 50) Severe (< 30) PR VGPR CR *P value for OS; vs no renal impairment. P = NS for PFS.

10. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Len/Dex in Relapsed/Refractory MM and Renal Impairment: MM-009/MM-010 Weber DM, et al. ASCO 2008. Abstract 8542. Grade 3/4 AE Degree of Renal Impairment (CrCl mL/min), % None (≥ 80) Mild (≥ 50 to < 80) Moderate (≥ 30 to < 50) Severe (< 30) Neutropenia31394338 Thrombocytopenia716*19*38 † Anemia411*24 † 44 † VTE1112146 GI disorders12919 Pneumonia961025* *P <.05 vs no renal impairment. † P <.001 vs no renal impairment.

11. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma MM-009/010 Phase III Trials: Survival 1. Weber DM, et al. N Engl J Med. 2007;357:2133-2142. 2. Dimopoulos M, et al. N Engl J Med. 2007;357:2123-2132. Len/DexDex AloneHR (95% CI)Log Rank P Value MM-009 [1] (n = 177)(n = 176) Median OS29.620.20.44 (0.30-0.65)<.001 MM-010 [2] (n = 176)(n = 175) Median OSNot reached20.60.66 (0.45-0.96)<.001

12. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma MM-009/010 Phase III Trials of Len/Dex in Relapsed/Refractory MM: Grade 3/4 AEs Weber DM, et al. N Engl J Med. 2007;357:2133-2142. Dimopoulos M, et al. N Engl J Med. 2007;357:2123-2132. 35 30 25 20 15 10 5 0 VTE Thrombocytopenia NeutropeniaAnemia Len/dex (MM-009) Dex (MM-009) Len/dex (MM-010) 40 45 Dex (MM-010)

13. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Lenalidomide/Doxorubicin/Dexamethasone in Relapsed/Refractory MM: Phase I/II Trial  N = 69  73% ORR  Grade 3/4 AEs –Anemia: 16.5% –Leukopenia: 36.5% –Neutropenia: 48.0% –Thrombocytopenia: 38.0% –Infection: 10.5%  Del(17p) and elevated β 2 -microglobulin associated with significantly inferior responses and shorter TTP Knop S, et al. Blood. 2009;113:4137-4143. Pts (%) Response Rates 60 50 40 30 20 10 0 70 80 ORRCRVGPRPD

14. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Lenalidomide Dosing for MM Pts With Renal Impairment  Moderate renal impairment (30 ≤ CrCl / < 60 mL/min) –10 mg once daily  Severe renal impairment (CrCl < 30 mL/min; not requiring dialysis) –15 mg q 48 hrs  End-stage renal disease (CrCl < 30 mL/min; requiring dialysis) –5 mg once daily; on dialysis days, administer dose following dialysis  After initiation of lenalidomide, subsequent dose modification should be based on ability of individual pt to tolerate treatment Lenalidomide [package insert].

15. Bortezomib-Containing Regimens

16. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Phase III APEX Trial: Bortezomib vs High- Dose Dexamethasone in Relapsed MM Richardson P, et al. N Engl J Med. 2005;352:2487-2498. Pts with relapsed MM following 1-3 therapies, not refractory to dexamethasone (N = 669) Dexamethasone 40 mg PO* Days 1-4, 9-12, and 17-20 for four 5-wk cycles (n = 336) Bortezomib 1.3 mg/m 2 IV Days 1, 4, 8, 11 for eight 3-wk cycles (n = 333) Treatment for 280 days *Pts who progressed on dexamethasone allowed to cross over to receive bortezomib in a companion study. Dexamethasone 40 mg PO Days 1-4 for four 5-wk cycles Bortezomib 1.3 mg/m 2 IV Days 1, 8, 15, 22 for three 5-wk cycles Treatment for 273 days Induction Maintenance

17. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Bortezomib in Myeloma Pts With Renal Impairment Jagannath S, et al. Cancer. 2005;103:1195-1200. CrCl, mL/minORR, %Grade 3/4 AEs, %Discontinuation, % ≤ 50 (n = 42) 25 Thrombocytopenia: 33 Neutropenia: 17 Peripheral neuropathy: 13 38 51-80 (n = 99) 33 Thrombocytopenia: 27 Neutropenia: 15 Peripheral neuropathy: 9 22 > 80 (n = 105) 45 Thrombocytopenia: 30 Neutropenia: 12 Peripheral neuropathy: 11 28

18. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Bortezomib and Del(13) in Myeloma 1. Richardson PG, et al. N Engl J Med. 2003;348:2609-2617. 2. Jagannath S, et al. Leukemia. 2007;21:151-157. 3. Richardson P, et al. N Engl J Med. 2005;352:2487-2498. *FISH data excluded; del(13) detected in 3/37 FISH-evaluated pts.  SUMMIT trial [1,2] : matched pair analysis by metaphase cytogenetics* –Del(13) had no significant effect on response rate or survival  APEX trial [2,3] : matched pair analysis of 21 del(13) pts vs 41 without del(13) –Response rate not significantly different between groups in either treatment arm –Del(13) associated with significant decrease in survival in dexamethasone arm –Del(13) had no effect on survival

19. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Phase III APEX Trial: Bortezomib Toxicity Richardson P, et al. N Engl J Med. 2005;352:2487-2498. Pts (%) Diarrhea Vomiting Pyrexia Thrombocytopenia Anorexia Neutropenia Dyspnea Paresthesia 0204060 Grade 4 Grade 3 Grade 1/2 Nausea Constipation Peripheral Neuropathy

20. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Richardson P, et al. Blood. 2007;110:3557-3560. Phase III APEX Trial: OS (Extended Follow-up)  Median OS –Bortezomib: 29.8 mos –Dexamethasone: 23.7 mos –P =.027  > 62% of dexamethasone-treated pts crossed over to receive bortezomib –1-yr survival rate 80% for bortezomib vs 67% for dexamethasone (P =.001)

21. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Bortezomib ± PLD in Relapsed/Refractory Myeloma (MMY-3001 Phase III Trial) Orlowski RZ, et al. J Clin Oncol. 2007;25:3892-3901. Pts with relapsed/ refractory MM, PS 0-1, bortezomib naive (N = 646) Treatment continued for 8 cycles or until disease progression or unacceptable toxicity Bortezomib 1.3 mg/m 2 Days 1, 4, 8, 11 (n = 322) Bortezomib 1.3 mg/m 2 Days 1, 4, 8, 11 PLD 30 mg/m 2 Day 4 (n = 324) Day 21 Primary endpoint: time to disease progression Secondary endpoints: OS, PFS, response rate, safety

22. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Orlowski RZ, et al. J Clin Oncol. 2007;25: 3892-3901. Bortezomib ± PLD in Relapsed/Refractory Myeloma (MMY-3001): TTP  Median TTP –PLD + bortezomib: 9.3 mos –Bortezomib: 6.5 mos –HR: 1.82 (95% CI: 1.41-2.35) – P =.000004

23. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Orlowski RZ, et al. J Clin Oncol. 2007;25:3892-3901. Bortezomib ± PLD in Relapsed/Refractory Myeloma (MMY-3001): OS  PLD + bortezomib associated with OS advantage relative to bortezomib alone –HR: 1.406 (95% CI: 1.002-1.1972; P =.0476 )  15-month OS –PLD + bortezomib: 76% –Bortezomib: 65% –P =.03

24. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma VMPT in Relapsed/Refractory Myeloma  Phase I/II multicenter, noncomparative, open-label study of VMPT evaluated as second-line (n = 14) or third-line (n = 16) therapy for relapsed/refractory myeloma  VMPT schedule (six 5-wk cycles) –Bortezomib at 3 dose levels (1.0 mg/m 2, 1.3 mg/m 2, or 1.6 mg/m 2 ) on Days 1, 4, 15, and 22 –Melphalan 6 mg/m 2 on Days 1-5 –Prednisone 60 mg/m 2 on Days 1-5 –Thalidomide 50 mg on Days 1-35 –Rest period on Days 23-35 Palumbo A, et al. Blood. 2007;109:2767-2772.

25. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma 1. Palumbo A, et al. Blood. 2007;109:2767-2772. 2. Gay F, et al. ASH 2009. Abstract 3887. VMPT in Relapsed/Refractory Myeloma: Best Response  68% of patients achieved best response within first 3 treatment cycles [1]  Reducing bortezomib dosing to once weekly in VMPT or VMP regimens reduces incidence of PN and maintains high CR rate relative to twice weekly dosing in elderly patients [2]

26. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Phase II Study of Len/Bort/Dex in Relapsed/Refractory Myeloma  N = 62  ORR (CR/nCR + PR + MR): 84% –Including 21% CR/nCR and 68% CR/nCR/VGPR/PR  No significant differences in response rates according to –Baseline cytogenetics and disease stage –Previous therapies and being refractory to previous therapy  Toxicities: mainly grade 1/2 myelosuppression –Attributable nonhematologic toxicities include grade 3 PN (n = 1), DVT (n = 2), grade 3 atrial fibrillation (n = 2) Richardson PG, et al. ASCO 2009. Abstract 8536.

27. New Aspects of Supportive Care

28. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Supportive Therapies in Myeloma  Bone disease –Radiotherapy for palliation of bone pain –Vertebroplasty or kyphoplasty for persistent pain –Bisphosphonates  Anemia: transfusions and/or RBC growth factors –Consider EPO trial in patients with symptomatic anemia  Hypercalcemia: rehydration, bisphosphonates  Renal dysfunction or hyperviscosity –Rehydration, treat infection, plasmapheresis  Infections: antibiotics, influenza vaccination Smith A, et al. Br J Haematol. 2005;132:410-451.

29. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Bisphosphonates: Efficacy  Reduced incidence of SREs and need for RT [1]  Zoledronic acid 4 mg 15-min infusion at least as effective as pamidronate 90 mg 2-hr infusion in reducing risk of skeletal-related events in patients with multiple myeloma [2] 1. Berenson JR, et al. Cancer. 2001;91:1191-1200. 2. Rosen LS, et al. Cancer J. 2001;7:377-387.

30. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Bisphosphonates: Toxicities  Long-term treatment associated with osteonecrosis of the jaw [1] –Risk higher with zoledronic acid  Dose- and infusion rate–related renal toxicity [2] –Modified dosing regimens under investigation [3] 1. Dimopoulos MA, et al. Haematologica. 2005;91:968-971. 2. Berenson JR. Oncologist. 2005;10:52-62. 3. Berenson JR, et al. ASH 2005. Abstract 5152.

31. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma VTE Risk With EPO or ASA: Analysis of MM-009 and MM-010 Data Weber DM, et al. ASH 2007. Abstract 412. Treatment VTE Incidence Len/Dex, % (n/N) (n = 353) P ValueDex, % (n/N) (n = 353) P Value No EPO12 (25/217).33 2 (6/245).04 EPO15 (21/136)8 (8/105) No ASA13 (46/345).60 5 (16/335) 1.00 ASA*0 (0/8)0 (0/15) *Prophylactic use in Month 1.

32. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Incidence and Prophylaxis of Thrombosis With IMiD-Based Therapies Incidence of VTE Within First 4 Mos of Therapy (%) 30 20 10 0 T Alone No prophylaxis Warfarin 1 mg/day Warfarin 1.25 mg/day Warfarin (full dose; INR 2-3) ASA Prophylactic LMWH Dex Alone VAD T + DexT + Dox Rajkumar SV, et al. Mayo Clin Proc. 2005;80:1549-1551.

33. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Risk Assessment for VTEs in MM Patients Receiving Thal or Len – Individual Factors  Obesity (BMI ≥ 30 kg/m 2 )  Previous VTE  Central venous catheter or pacemaker  Surgery –General surgery –Any anesthesia –Trauma  Associated disease –Cardiac disease –Chronic renal disease –Diabetes –Acute infection –Immobilization  Blood clotting disorders Palumbo A, et al. Leukemia. 2008;22:414-423.

34. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma  VTE prophylaxis for individual risk factors or myeloma- related risk factors (eg, hyperviscosity) –If ≤1 risk factor present: aspirin 81-325 mg/day –If ≥ 2 risk factors present: LMWH (equivalent to enoxaparin 40 mg qd) or full-dose warfarin (target INR: 2-3)  VTE prophylaxis for myeloma therapy–related risk factors (eg, high-dose dexamethasone, doxorubicin, multiagent chemotherapy) –LMWH (equivalent to enoxaparin 40 mg/day) or full-dose warfarin (target INR: 2-3) Palumbo A, et al. Leukemia. 2008;22:414-423. Risk Assessment for VTEs in MM Patients Receiving Thal or Len

35. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma LMWH vs Warfarin vs ASA in IMiD-Treated Myeloma Pts: VTE by Risk Factors Palumbo A, et al. ASH 2007. Abstract 310. Pts (%) ASA 0136 ≥ 2 risk factors 1 risk factor 0 risk factors LMWH WAR 254

36. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Len/Dex: Cytopenia Management  Monitoring CBCs –At least biweekly monitoring –Standard dose-reductions  Neutropenia –For grade ≥ 3, monitor WBCs and consider G-CSF prophylaxis or lenalidomide dose reduction  Thrombocytopenia –For grade ≥ 3, monitor WBCs and consider interrupting treatment or dose reductions  Anemia –Use ESAs for Hgb < 10 g/dL Palumbo A, et al. 2007 EHA. Abstract 265.

37. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma PN Following Bortezomib Treatment in Advanced Myeloma  PN (treatment emergent or worsening of baseline PN) identified in 90 of 256 (35%) pts with relapsed/refractory MM enrolled in 2 phase II trials of bortezomib –~ 82% had preexisting PN –4% of pts without preexisting PN developed grade 3 PN vs 14% with preexisting PN –Of 35 pts with ≥ grade 3 PN, 71% experienced improvement or resolution to baseline –PN led to dose reduction in 12% and discontinuation in 5% Richardson PG, et al. J Clin Oncol. 2006;24:3113-3120.

38. Clinical Trials of Novel Agents and Combinations

39. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Overview of Novel Agents  HSP90 inhibitors –Tanespimycin  Monoclonal antibodies –Elotuzumab (HuLuc63) –CNTO 328  Proteasome inhibitors –Carfilzomib  IMiDs –Pomalidomide  HDAC Inhibitors –Vorinostat

40. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Phase I/II Study of Tanespimycin + Bortezomib in Relapsed/Refractory Myeloma Best ResponseCR + PR + MR, n (%) Total (N = 67*)18 (27) Bortezomib Status at Study Entry Naive (n = 21)10 (48)  ≤ 3 previous regimens (n = 11)7 (64)  ≥ 4 prior regimens (n = 10)3 (30) † Pretreated (n = 23)5 (22) Refractory (n = 23)3 (13) Richardson PG, et al. ASCO 2009. Abstract 8503. * Evaluable pt cohort excludes 2 pts with no M protein at baseline and 3 pts who received lowest doses of tanespimycin + bortezomib † Includes 1 pt who received a SCT prior to 6-wk confirmation of response.

41. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma 1. Lonial S, et al. IMWG 2009. Poster. 2. Lonial S, et al. ASH 2009. Abstract 432. Elotuzumab (HuLuc63) + Len/dex in Relapsed MM  Phase I/II: N = 28 [2] –ORR: 82% (95% in 22 pts without previous lenalidomide) –MTD not reached with highest dose at 20 mg/kg –Elotuzumab-related infusion rxn as SAE: n = 2 Phase IB Response [1] Cohort 1 5 mg/kg (n = 3) Cohort 2 10 mg/kg (n = 3) CR00 VGPR10 PR12 No change (SD)11 PD00 50 Phase Ib [1] 0 -50 -100 M-protein % of Baseline Study Visit C1D1 C1D22C2D1C2D22C3D1C4D1 C4D15 C5D1C6D1 Pt 1 Pt 4 Pt 2 Pt 5 Pt 3 Pt 6

42. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma CNTO 328 + Bort in Relapsed/Refractory MM: Safety and Efficacy (Phase II Study) Rossi JF, et al. ASH 2008. Abstract 867. AE, %Any Grade Grade 3/4 Neutropenia7671 Anemia290 Thrombocytopenia5238 Fatigue385 Infection6224 Diarrhea575 Neuropathy385 57% ORR N = 21 29% n = 3 n = 6 Median TTP: 8.7 mos (range: 8.7 to > 22.4) 50 40 30 20 10 0 60 ORR CR VGPR PR SD PD N = 21

43. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Vij R, et al. ASH 2008. Abstract 865. Time to Best Response AE, %Any Grade Grade 3/4 Neutropenia3210.0 Anemia296.5 Thrombocytopenia236.5 Shortness of breath296.5 33.5% ORR 18.0% ORR 57.0% ORR 60 50 40 30 20 10 0 70 All (N = 31) Prior Bort (n = 17) ORR CR VGPR PR SD PD MR No Prior Bort (n = 14) Carfilzomib in Relapsed/Refractory MM: Safety and Efficacy (Phase II Study)  Most common AEs (any grade): fatigue, nausea, vomiting, insomnia, fever, diarrhea, headache, cough, low magnesium, hypoesthesia  1 pt experienced persistent grade 1 PN with carfilzomib

44. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Grade 3/4 AE [1] Pts, n Neutropenia19 Febrile neutropenia4 Leukopenia10 Thrombocytopenia2 Fatigue10 Diarrhea1 Hyperglycemia3 Peripheral neuropathy1 Cardiovascular thrombosis1 63% ORR 40% ORR 1. Lacy MQ, et al. J Clin Oncol. 2009;27:5008-5014. 2. Lacy MQ, et al. ASH 2009. Abstract 429. 60 50 40 30 20 10 0 70 All Pts [1] (N = 60) Len Refractory [1] (n = 20) Pomalidomide + Low-Dose Dex in Relapsed/Refractory MM: Safety & Efficacy  Phase II study in 34 lenalidomide-resistant/refractory pts [2] –Confirmed response rate: 32% –Most frequent grade 3/4 AEs: neutropenia: 26%; anemia: 12% ORR CR VGPR PR

45. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Vorinostat + Bortezomib in Relapsed/ Refractory MM: Ph I Results  Well tolerated; AEs included fatigue, GI symptoms (diarrhea), thrombocytopenia Summary of Efficacy Response, %Trial 1 (n = 33)* Trial 2 (n = 21)* ORR3843 MR170 SD3947 PD610 Weber D, et al. ASH 2008. Abstract 871. Jagannath S, et al. ASH 2009. Abstract 3886. Response in Bortezomib- Refractory Patients Response, %Trial 1 (n = 7) Trial 2 (n = 8) CR00 VGPR00 PR2938 MR290 SD4250 PD012 *Evaluable patients.

46. clinicaloptions.com/oncology Spanning the Continuum of Care in Multiple Myeloma Conclusion  Regimens containing lenalidomide or bortezomib have shown efficacy in relapsed/refractory myeloma  Selection of regimens should be a rational process, based on pt characteristics  Supportive care is an important aspect of the care of these pts

47. Go Online for More CCO Coverage of Multiple Myeloma Interactive Virtual Presentations review and consider challenging patient cases with guidance from expert faculty members Text-Based Modules plus downloadable PowerPoint slides clinicaloptions.com/oncology