Living Well with Myeloma Teleconference Series Thursday, March 24 th :00 PM Pacific/5:00 PM Mountain 6:00 PM Central/7:00 PM Eastern

Transcription

1 Living Well with Myeloma Teleconference Series Thursday, March 24 th 216 4: PM Pacific/5: PM Mountain 6: PM Central/7: PM Eastern

2 Speakers Dr. Brian Durie, IMF Chairman Cedars Sinai Samuel Oschin Cancer Center Los Angeles, CA Dr. Rafat Abonour Indiana University Simon Cancer Center Indiana, IN Dr. Vincent Rajkumar Mayo Clinic Rochester, MN 2

3 Top Questions Needing Answers Episode 1! 1. How to use newly approved agents: Farydak (panobinostat) Darzalex (daratumumab) Ninlaro (ixazomib) Empliciti (elotuzumab) 2. Are CAR-T cells the future best therapy? International Myeloma Foundation 3

4 Agents for Discussion Today Agent Use Combination Farydak (panobinostat) Relapse/Refractory + Velcade / Dexamethasone Darzalex (daratumumab) Ninlaro (ixazomib) Relapse/Refractory 1 prior regimen Single agent + Revlimid / Dexamethasone Empliciti (elotuzumab) Relapse: 1-3 prior regimens + Revlimid / Dexamethasone International Myeloma Foundation 4

5 The Decision Process* Clinical experience Data from research DECISION EVIDENCE-BASED MEDICINE Sackett DL & al., «Evidence based medicine: what it is and what it isn't» BMJ, vol. 312, no 723, janvier 1996 International Myeloma Foundation Patient preferences *Philippe Moreau ASH 215 5

6 Treatment Approaches in Relapsed/Refractory MM First relapse Participate in clinical trials with novel agents IMiD-based regimen Underlying PN Prior IMiD use with durable/deep response Prior bortezomib use PI-based regimen Prior IMiD use Prior bortezomib use with durable/deep response Translocation (4;14) Autologous transplant Long remission post 1st transplant (>18 24 months) Transplant not part of primary therapy Len-naïve KRd, IRd Elo-Rd (high risk) Bor-naïve Kd, KRd, IRd Len/Bor-exposed Pano-Vd Usmani SZ, Lonial S. Clin Lymphoma Myeloma Leuk. 214;14 Suppl:S71. 6

7 Treatment Approaches in Relapsed/Refractory MM second relapse Participate in clinical trials with novel agents Chemotherapy for rapid relapse IMiD- or PI-based regimen Transplant VTD-PACE, DT-PACE, DCEP Especially for extramedullary disease, secondary plasma cell leukemia Carfilzomib/ Dex ± IMiD Pomalidomide/ Dex ± PI PI preference for translocation (4;14) Autologous: usually a short-term fix Allogeneic: for select group, in a clinical trial setting Dual (Len/Bor) refractory OR >3 prior Lines Daratumumab Usmani SZ, Lonial S. Clin Lymphoma Myeloma Leuk. 214;14 Suppl:S71. 7

8 Summary of Combination Therapy at Relapse RD* 1 ORR 6 Median Lines of Tx: KRd* 2 RVD* PVd 4 85 Vd* 5 CyBorD CRD 7 CPd Pd* 9 31 Kd 1 KPd ORR (%) *Data from phase 3 trials, all others from phase 1 or 2 trials 1. Dimopoulos M et al. N Engl J Med. 27;357: Stewart AK et al. N Engl J Med. 215;372: Richardson PG et al. Blood. 214;123: Lacy MQ et al. Blood Abstract Mikhael JR et al. Br J Haematol. 29;144: Monge J et al. J Clin Oncol Abstract Morgan GJ et al. Br J Haematol. 27;137: Baz R et al. Blood Abstract San Miguel J et al. Lancet Oncol. 213;14: Lendvai N et al. Blood. 214;124: Shah JJ et al. Blood Abstract 69. 8

9 Summary of Combination Therapy at Relapse PFS/TTP RD* 1 11 NR Median Lines of Tx: OS KRd* 2 RVD* PVd 4 11 NR CyBorD CPd 8 1 NR 4 Pd* Kd KPd Survival (Mos)

10 How to use Farydak (panobinostat) International Myeloma Foundation 1

11 PANORAMA1 Study Design 21-day cycles Randomization N=768 Stratification: Number of previous treatment lines Prior bortezomib Pano-Vd Panobinostat 2 mg Days 1, 3, 5, 8, 1, 12 Bortezomib 1.3 mg/m 2 Days 1, 4, 8, 11 Dexamethasone 2 mg Days 1, 2, 4, 5, 8, 9, 11, 12 Vd Bortezomib 1.3 mg/m 2 mg Days 1, 4, 8, 11 Dexamethasone 2 mg Days 1, 2, 4, 5, 8, 9, 11, 12 BOR NAÏVE OR BOR SENSITIVE San Miguel JF et al. Lancet Oncol. 214;15:

12 PANORAMA1 Results Pano-Vd (n=387) Vd (n=381) HR P Value Median PFS, mos <.1 ORR, % ncr, % <.1 IMiD + bortezomib, mos IMiD + bortezomib + 2 prior lines, mos AEs, % G3 Diarrhea 25 7 G3 Asthenia G3 PN Benefit less pronounced in women and patients > 65 years BUT more evident in patients who with previous exposure to bortezomib and immunomodulatory agent. San Miguel JF et al. Lancet Oncol. 214;15:

13 Summary of Other Notable HDAC Combinations Outcomes Regimen Phase (N) ORR CBR Ricolinostat ± bortezomib + dexamethasone 1 1 (2) 25% (heavily pretreated) 6% (2 pts VGPR, 3 pts PR, 2 pts MR, 5 pts SD) Ricolinostat + lenalidomide + 1 (22) 64% dexamethasone 2 1% (1 pt CR, 5 pts VGPR, 8 pts PR, 3 pts MR, 5 pts SD) Panobinostat + carfilzomib + 1 (36) 77% dexamtheasone 3 88% (1 pt CR, 1 pts VGPR, 16 pts PR, 4 pts MR, 4 pts SD) 1. Raje N et al. Blood. 213;122. Abstract Raje N et al. EHA 214. Abstract P Berdeja JG et al. J Clin Oncol. 215;33. Abstract

14 When do you recommend panobinostat? International Myeloma Foundation 14

15 Targets on the Myeloma Cell Surface SLAMF7 CD38 15

16 What s Dara? CD38 Daratumumab is an IV human IgG manufactured antibody It is a targeted immunotherapy which binds to CD38 16

17 Efficacy in Combined Analysis ORR, % PR VGPR CR scr ORR = 31% 2% 1% 3% CR or better 13% 1% VGPR or better 1 18% 5 16 mg/kg N = 148 ORR was consistent in subgroups including age, number of prior lines of therapy, refractory status, or renal function 17

18 Progression-free Survival Patients progression-free and alive, % Responders MR (Minimal Response)/SD (Stable Disease) PD (Progressive Disease)/NE (Non-Evaluable) Responders (Median ~7.4 months) MR/SD: 3.2 ( ) months PD (median ~.9 months) Patients at risk Responders MR/SD PD/NE Time from first dose, months

19 Overall Survival 1 Patients alive, % 75 5 Responders MR/SD 25 PD Responders MR/SD PD/NE Patients at risk Responders MR/SD PD/NE Time from first dose, months For the combined analysis, median OS = 19.9 months 1-year overall survival rate = 69% (95% CI, ) 19

20 When do you recommend DARA? International Myeloma Foundation 2

21 What about Ixazomib (Ninlaro )? International Myeloma Foundation 21

22 TOURMALINE-MM1 Study Design 28-day cycles Randomization N=722 Stratification: Number of prior therapies PI exposure ISS stage IRd Ixazomib 4 mg Days 1, 8, 15 Lenalidomide 25 mg Days 1 21 Dexamethasone 4 mg Days 1, 8, 15, 22 Rd Lenalidomide 25 mg Days 1 21 Dexamethasone 4 mg Days 1, 8, 15, 22 LEN NAÏVE OR LEN SENSITIVE Moreau P et al. Presented at: 57th ASH Annual Meeting & Exhibition. Orlando, FL; December 215. Abstract

23 TOURMALINE-MM1 Results I-Rd (n=36) Rd (n=362) HR P Value Median PFS, mos ORR, % VGPR, % AEs, % G3 Diarrhea 6 2 G3 PN 2 2 Benefit with IRd was also noted in pts with high-risk cytogenetics. Moreau P et al. Presented at: 57th ASH Annual Meeting & Exhibition. Orlando, FL; December 215. Abstract

24 When do you recommend Ixazomib (Ninlaro )? International Myeloma Foundation 24

25 What s Elo? Elotuzumab (HuLuc63) is an IV humanized monoclonal antibody targeting human SLAMF7, a cell surface glycoprotein. CD16 Elotuzumab Hsi ED et al. Clin Cancer Res. 28;14: Tai YT et al. Blood. 28;112: van Rhee F et al. Mol Cancer Ther. 29;8: Lonial S et al. Blood. 29;114:432. Richardson PG, et al. ASH 214. Abstract 32 25

26 ELOQUENT-2: Elotuzumab With Lenalidomide/Dexamethasone R/R MM Randomized, open-label, multicenter phase III trial Pts with relapsed MM and 1-3 prior treatments Elotuzumab 1 mg/kg IV QW cycles 1, 2 then Q2W + Lenalidomide 25 mg PO D Dexamethasone 4 mg PO QW (n = 321) 28-day cycles (N = 646) Lenalidomide 25 mg PO D Dexamethasone 4 mg PO QW (n = 325) Until Progression or unacceptable toxicity Primary endpoints: Progression Free time (PFS), Overall Response Secondary endpoints: Overall Survival, safety, health-related Quality of Life Dimopoulos MA, et al. ASH 215. Abstract

27 ELOQUENT-2: Progression Free and Overall Response Probability Progression Free Response Rate (%) Mos P =.2 1 Elo-Rd Rd ORR* 1-yr PFS 68% 57% Combined Response (scr + CR + VGPR) 2-yr PFS 4 41% 27% 7 CR (scr + CR ) VGPR Elo-Rd Rd Median PFS, mos (95% CI) ( ) ( ) PR Lonial S, et al. N Engl J Med 215; 373: Elo-Rd Rd 27

28 When do you recommend Elo? International Myeloma Foundation 28

29 CAR T Immune Therapy 29

30 T cells CAR-T are white blood cell cells therapy that attack and 11 kill viruses and cancer cells I hope Chimeric antigen receptors (CARs) help T-cells recognize and destroy cancer cells 1. T cells are collected from the patient. A machine removes the desired cells from the blood, then returns the rest back to the patient. 3

31 CAR-BCMA T Cells in Myeloma: Background T cells can be genetically modified to express chimeric antigen receptors (CARs) specific for malignancy-associated antigens B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells. BCMA is a potential target for CAR T-cell therapy for MM T Cell AntiBCMA T Cell AntiBCMA T Cell AntiBCMA T Cell AntiBCMA The patient s own T-cells were stimulated, transduced with CAR-BCMA retroviruses, and cultured for 9 days before infusion. Study presented ASH 215 evaluated CAR- BCMA T cell infusion for treatment of advanced MM 1. Carpenter RO, et al. Clin Cancer Res. 213;19: Ali SA, et al. ASH 215. Abstract LBA-1. 31

32 CAR-BCMA T Cells in Myeloma: Study Design First-in-human phase I trial Pts with advanced relapsed/ refractory MM More than 3 prior lines of therapy; BCMA expression on myeloma cells 12 patients enrolled Cyclophosphamide 3 mg/m 2 Fludarabine 3 mg/m 2 QD for 3 days CAR-BCMA T cells* Single infusion *Dose escalation of CAR+ T cells/kg.3 x x x x 1 6 Ali SA, et al. ASH 215. Abstract LBA-1. 32

33 CAR-BCMA T Cells in Myeloma: Response to therapy Response to Therapy Stringent complete response(scr) Number of Patients (total 12 treated) 1 Very good partial response VGPR 1 Partial response 2 Stable disease 8 Ali SA et al. Proc ASH 215;Abstract LBA1. 33

34 SO: Are CAR-T cells worth all the hype? Does high risk make a difference? What other therapies can play an important role? International Myeloma Foundation 34

35 Support International Myeloma Foundation 35

36 International Myeloma Foundation