Making Sense of Myeloma Treatment Advances

Transcription

1 Making Sense of Myeloma Treatment Advances Webinar 1, May 17, 217 Updates From the 16th International Myeloma Workshop and the American Association for Cancer Research 217 Annual Meeting Speakers Moderator: Mary DeRome Multiple Myeloma Research Foundation Norwalk, Connecticut Faculty: Lawrence Boise, PhD Emory University Atlanta, Georgia Shaji Kumar, MD Mayo Clinic Rochester, Minnesota 1

2 Topics for Discussion Disease biology and risk stratification Newly diagnosed myeloma Stem cell transplantation Minimal residual disease (MRD) in myeloma Relapsed myeloma Venetoclax New immune therapies Myeloma Treatment Paradigm SCT Eligible SCT Ineligible Diagnosis & Risk Stratification Induction Consolidation Maintenance Induction followed by continuous therapy Treatment of relapsed disease Treatment-free interval? Tumor Burden SCT, stem cell transplant 2

3 Disease Biology and Risk Stratification Asymptomatic Myeloma What factors control progression? Up-front genetics? Acquired changes? Other factors? 3

4 Acquired Changes in Myeloma pre MGUS MGUS AMM MM B In this model a change to a cell with asymptomatic disease results in symptomatic myeloma. A Seckinger A et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-15. Up-Front Genetics in Myeloma pre MGUS MGUS AMM MM MGUS AMM MM B In this model the genetic changes occur earlier and other factors determine when the disease becomes symptomatic Seckinger A et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-15. 4

5 Tumor Mass, Proliferation, and Up-Front Factors Are Predictors of Progression to Symptomatic Myeloma M protein Doubling time UAMS7 gene score Seckinger A et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-15. Disease Progression: More Than One Way to Evolve Neutrally evolving Darwinian selection (Non-neutral) Johnson D et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-16. 5

6 Neutral-Evolution Disease Responds Differently to Non-Intensive Therapy Intensive Treatment Overall Survival Median not reached Non-intensive Treatment Overall Survival Median 27.3 vs months (P<.1) Johnson D et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-16. Using Next-Generation Sequencing for Myeloma Staging Standard Risk Factors for MM and the R-ISS Prognostic Factor ISS stage I II III CA by ifish High risk Standard risk LDH Normal High Criteria Serum β2m <3.5 mg/l serum albumin 3.5 g/dl Not ISS stage I or III Serum β2m 5.5 mg/l Presence of del(17p) and/or translocation t(4;14) and/or translation t(14;16) No high-risk CA Serum LDH < the upper limit of normal Serum LDH > the upper limit of normal A new model for risk stratification for MM R-ISS stage I ISS stage I and standard-risk CA by ifish and normal LDH II Not R-ISS stage I or III III ISS stage III and either high-risk CA by ifish or high LDH CA, chromosomal abnormalities; ifish, interphase fluorescent in situ hybridization; ISS, International Staging System; LDH, lactate dehydrogenase; MM, multiple myeloma; R-ISS, revised International Staging System. Fiala M et al. Presented at the 16th International Myeloma Workshop, March 1-4, 217. Abstract OP-29. Palumbo A, et al. J Clin Oncol. 215;33:

7 Using Next-Generation Sequencing for Myeloma Staging Data: Interim analysis 9 from the MMRF CoMMpass study. Controlling for Age (>65 vs 65) and Sex Fiala M et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-29. Sequencing From the Blood (or do we need to do so many bone marrows?) Circulating tumor cells (CTCs) are rare myeloma plasma cells found in the blood Circulating free DNA (cfdna) is DNA released from dead cells into the bloodstream 733 non-silent mutations cfdna 8% BM cells 1% 63% CTCs 7% Sequencing from CTCs or cfdna can provide similar results to sequencing from the bone marrow Manier S et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-4. 7

8 Making Sense of Myeloma Treatment Advances Developing New Ways to Measure Disease Current standard methods for measuring M protein in the blood or urine were developed in the 196s New antibody therapies interfere with these methods Intensity Purify Ig using Camelids +2 miramm Screen + MRD* Screen Mass (Da) +1 Release of light chain DTT Analyze on MASS-FIX Inject on microlc miramm MRD T mabs Mass reconstruction Using mass spectrometry to measure antibodies or light chains is more sensitive (MRD) and more precise (no therapeutic antibody interference). 1 X IFE ESI Intensity Intensity Analyze on 56 Q-TOF MS m/z 22,85.7 Da M-protein (mig) Polyclonal LCs Mass (Da) MFMER slide 13 Murray D et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-3. Newly Diagnosed Myeloma 8

9 SWOG S777: VRd vs Rd Eight 21-Day Cycles of VRd Randomization N=525 Stratification: ISS (I, II, III) Intent to progression (yes/no) Bortezomib 1.3/mg 2 IV Days 1, 4, 8, and 11 Lenalidomide 25 mg/day PO Days 1-14 Dexamethasone 2 mg/day PO Days 1, 2, 4, 5, 8, 9, 11, 12 Six 28-Day Cycles of Rd Lenalidomide 25 mg/day PO Days 1-21 Dexamethasone 4 mg/day PO Days 1, 8, 15, 22 Lenalidomide 25 mg/day PO Days 1-21 Dexamethasone 4 mg/day PO Days 1, 8,15, 22 ISS, International Staging System; Rd, lenalidomide + dexamethasone; SWOG, Southwest Oncology Group; VRd, bortezomib + lenalidomide + dexamethasone Durie BG et al. Lancet. 217;389:519. Response and Survival Outcomes Progression free survival Overall Survival Durie BG et al. Lancet. 217;389:519. 9

10 CLARION Study Design Randomization 1:1 N=955 Stratification: ISS stage Route of bortezomib administration (if randomized to VMP) Region Age Maximum 9 cycles KMP Carfilzomib* 36 mg/m 2 Days 1, 2, 8, 9, 22, 23, 29, 3 (2 mg/m 2 days 1, 2, cycle 1 only) IV over 3 minutes Melphalan 9 mg/m 2 and prednisone 6 mg/m 2 Days 1 4 Maximum 9 cycles VMP Bortezomib 1.3 mg/m 2 Days 1, 4, 8, 11, 22, 25, 29, 32 (Days 4, 11, 25, 32 omitted for cycles 5+) IV or SC Melphalan 9 mg/m 2 and prednisone 6 mg/m 2 Days 1 4 Primary end point: PFS Secondary end points: OS, CRR, ORR, grade 2 PN rate, HRQoL, safety and tolerability Exploratory end point: MRD *Carfilzomib was administered for 2 weeks out of 3 twice per cycle Melphalan dose was 7 mg/m 2 if age was >75 years or CrCL was 3 to <5 ml/min; 5 mg/m 2 if CrCl was 15 to <3 ml/min. Facon T et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-44. Proportion Event-Free Number at risk: KMP VMP Primary End Point: Progression-Free Survival KMP VMP Months Disease progression or death n (%) Median PFS months HR for KMP vs VMP (95% CI) Median follow-up time: 22.2 months for KMP and 21.6 months for VMP The absence of PFS difference was consistent across subgroups KMP (n=478) 27 (43.3) ( ) 1-sided P= VMP (n=477) 214 (44.9) 22.1 Facon T et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-44. 1

11 Secondary End Point: Response Rates Patients (%) Odds ratio (95% CI): 1.18 ( ) Odds ratio (95% CI): 1.65 ( ) 61.3% 49.3% Odds ratio (95% CI): 1.41 ( ) 84.3% 78.8% 25.9% 23.1% n=124 n=11 n=293 n=235 n=43 n=376 CRR ( CR) VGPR ORR ( PR) KMP VMP Median DOR: 25.2 months (95% CI, 21.3 NE) for KMP vs 22.8 months (95% CI, ) for VMP Facon T et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-44. Adverse Events Hematologic AE % KMP (n=474) VMP (n=47) All grade Grade 3 All grade Grade 3 Anemia Thrombocytopenia Neutropenia Febrile neutropenia Nonhematologic AE % ( 2% in either arm) Pyrexia Nausea Vomiting Diarrhea Constipation Peripheral neuropathy Facon T et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP

12 KMP Once-Weekly K, phase 1 Induction: 9 cycles of 35 days Carfilzomib (2 mg at D1C1 then or 7 mg/m² depending on cohort) Weekly IV (day 1,8,15,22) followed by a 13-day rest In combination with melphalan.25 mg/kg/d and prednisone 6 mg/m² by mouth on days 1 to 4 (patient diary) 13 days rest κ κ κ κ J1 J2 J3 J4 MP J8 Maintenance: J15 J22 Cycle 1 of 35 days Cycle 2 13 cycles of 28 days. Carfilzomib: 36 mg/m² twice a month (day 1 and 15) IV for 1 year MP, melphalan prednisone; κ, carfilzomib Leleu X et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-12. KMP With Weekly K The MTD of K will be at 7 mg/m 2 up to 75 years old, and 56 above The CR rate of KMP weekly is remarkable, possibly greater than previous reports of VMP and KMP (twice a week 36) Study Schema Design PI ORR, % CR, % IFM KMP Weekly C Carmysap 1 KMP Bi-Weekly 9 12 Vista 2 VMP Bi-Weekly Mateos 3 VMP Weekly C2 8 Palumbo 4 VMP VMPT-VT Weekly C (39 end maintenance) Moreau P et al. Blood. 215;125: San Miguel J et al. N Engl J Med. 28;359: Mateos MV et al. Lancet Oncol. 21;11: Palumbo A et al. J Clin Oncol. 21;28:511. Leleu X et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP

13 Champion-2 Study Design Carfilzomib 36, 45, or 56 mg/m 2 IV Days 1, 2, 8, 9, 15, 16 (2 mg/m 2 days 1, 2, cycle 1 only) Infusion duration: 3 minutes for all doses Cyclophosphamide 3 mg/m 2 oral Days 1, 8, 15 Dexamethasone 4 mg, oral or IV Days 1, 8, 15, day cycles 8 cycles, or progressive disease, unacceptable toxicity, or withdrawal of consent Boccia R et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-23. Champion-2 Best Overall Response and Time to Response 56 mg/m 2 dose cohort: ORR: 87.5% (95% CI, 61.7% 98.4%) Median time to response: 1 month (range, months) 36 mg/m 2 (N = 3) 45 mg/m 2 (N=3) 56 mg/m 2 (N=16) Best overall response, n (%) Stringent complete response Complete response Very good partial response Partial response Stable disease Progressive disease (.) (.) 1 (33.3) 1 (33.3) (.) 1 (33.3) (.) (.) 2 (66.7) 1 (33.3) (.) (.) (.) 1 (6.3) 7 (43.8) 6 (37.5) 2 (12.5) (.) Boccia R et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP

14 Transplant BMT CTN 72 Stem Cell Transplantation for Multiple Myeloma Incorporating Novel Agents: SCHEMA N=75 pts (25 in each arm) Lenalidomide maintenance Register and randomize MEL 2 mg/m 2 N=257 VRD 4* N=254 Lenalidomide maintenance MEL 2 mg/m 2 Lenalidomide maintenance *Bortezomib 1.3 mg/m 2 days 1, 4, 8,11 Lenalidomide 15 mg days 1 15 Dexamethasone 4 mg days 1, 8, 15 Every 21 days N=247 Lenalidomide 3 years : 1 mg/d for 3 cycles, then 15 mg/d Amendment in 214 changed Lenalidomide maintenance until disease progression after report of CALGB

15 Stamina: PFS 1 8 Probability, % month estimate and 95% CI Auto/Auto: 56.5 (49.4, 62.9) Auto/RVD: 56.7 (5., 62.8) Auto/Maint: 52.2 (45.4, 58.6) Stadtmauer EA et al. Blood. 216;128: Abstract LBA-1. Lenalidomide Maintenance: Meta-Analysis There is a 25% reduction in risk of death, representing an estimated 2.4-year increase in median survival (March 215 data cutoff) a Survival Probability Events/n LEN maint 215/65 Placebo/ Observation 275/63 Median OS (95% CI), mo HR (95% CI) P value NR (NR NR).75 (.63.9) ( ) 7-yr OS Overall Survival (Months) No. at Risk LEN maint Placebo/ Observation a Log-rank test and Cox model stratified by study to assess impact of lenalidomide maintenance on overall survival. Median for lenalidomide treatment arm was extrapolated to be 115 months based on median of the control arm and HR (median, 86 months; HR =.75). HR, hazard ratio; maint, maintenance; NR, not reached; OS, overall survival. Attal M et al. J Clin Oncol,. 216;34: Abstract 81. 5% 62% 15

16 Overall Survival: Subgroup Analysis LEN maint a Placebo/ Observation a HR (95% CI) < 6 y ( ) Age b 6 y ( ) Sex Male ( ) Female ( ) I/II ( ) ISS stage c III ( ) CR ( ) Response after ASCT (prior to maint) CR/VGPR (.54-.9) PR/SD d ( ) Normal LDH e ( ) > ULN ( ) Adverse-risk cytogenetics es ( ) at diagnosis f No ( ) < 5 ml/min CrCl at diagnosis g ( ) 5 ml/min ( ) < 5 ml/min ( ) CrCl after ASCT h 5 ml/min ( ) HR Favors LEN maint Favors placebo/ observation a Number of patients. b For CALGB and IFM, age at randomization is available/used. For GIMEMA, only age at diagnosis is available. c The ISS stage was based on β2 microglobulin and albumin at diagnosis for GIMEMA and IFM and at registration for the CALGB. d Four patients upon central review did not meet the criteria for SD. e LDH data were available only for IFM and GIMEMA. f Cytogenetic data were available only for IFM and GIMEMA. g The patients with missing CrCl at diagnosis data were in CALGB and IFM. h CrCl post-asct data were available only for CALGB and IFM. ASCT, autologous stem cell transplant; CR, complete response; CrCl, creatinine clearance; HR, hazard ratio; ISS, International Staging System; LDH, lactate dehydrogenase; LEN, lenalidomide; maint, maintenance; PR, partial response; SD, stable disease; ULN, upper limit of normal; VGPR, very good partial response. Attal M et al. J Clin Oncol,. 216;34: Abstract 81. Denosumab vs Zoledronic Acid HR (95% CI) =.98 (.85, 1.14); P=.1 (Noninferiority) Raje N et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP

17 Progression-Free Survival HR (95% CI) =.82 (.68,.99); P=.36 (Descriptive) Median duration (95% CI), months Denosumab (34.3, not estimable) Zoledronic acid (3.19, not estimable) Raje N et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-46. MRD in Myeloma 17

18 MRD Negativity: Daratumamab Results in Deeper Responses in Combinations with Revlimid or Velcade ITT population, % POLLUX CASTOR * * DRd Rd DRd Rd DRd Rd DVd Vd DVd Vd DVd Vd MRD negative MRD positive MRD negative MRD positive ITT population, % % of MRD-negative patients among those who achieved CR *P<.5; P<.5 Avet-Loiseau H et al. Blood. 216;128. Abstract 246. Relapsed Myeloma 18

19 ENDEAVOR: Study Design Randomization 1:1 N=929 Stratification: Prior proteasome inhibitor therapy Prior lines of treatment ISS stage Route of V administration Kd Carfilzomib* 56 mg/m 2 IV Days 1, 2, 8, 9, 15, 16 (2 mg/m 2 days 1, 2, cycle 1) Infusion duration: 3 minutes for all doses Dexamethasone 2 mg Days 1, 2, 8, 9, 15, 16, 22, day cycles until PD or unacceptable toxicity Vd Bortezomib 1.3 mg/m 2 (3 5 second IV bolus or subcutaneous injection) Days 1, 4, 8, 11 Dexamethasone 2 mg Days 1, 2, 4, 5, 8, 9, 11, day cycles until PD or unacceptable toxicity Treat to progression Treat to progression Primary end point: PFS by IRC Secondary end points: OS ORR DOR Grade 2 PN rate Safety * Carfilzomib was administered for 3 weeks out of 4 ISS, International Staging System; IV, intravenous; Kd, carfilzomib and dexamethasone; PD, progressive disease; Vd, bortezomib and dexamethasone; V, bortezomib. Siegel DS et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract PS-254. Primary End Point: Progression-Free Survival Proportion Surviving Without Progression Disease progression or death n (%) Median PFS months HR for Kd vs Vd (95% CI) Kd (n=464) 171 (37) (.44.65) 1-sided P<.1 Vd (n=465) 243 (52) Kd Vd Months Since Randomization Median follow-up: 11.2 months Siegel DS et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract PS

20 Overall Survival Proportion Surviving Kd Vd Death n (%) Median OS months HR for Kd vs Vd (95% CI) Kd (n=464) 189 (4.7) 47.6 Vd (n=465) 29 (44.9) ( ) 1-sided P= Months Number at risk: Kd Vd Siegel DS et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract PS-254. Pembrolizumab, Pomalidomide, Dexamethasone Characteristic N=48 Median lines of prior therapy (Range) >3 Prior therapy no. (%) ASCT Proteasome inhibitors Bortezomib Carfilzomib IMiDs Lenalidomide Refractory Proteasome inhibitors Lenalidomide Double-refractory to IMiDs and PI 3 (2-5) 13 (27%) 31 (72%) 48 (1%) 48 (1%) 24 (5%) 48 (1%) 48 (1%) 38 (79%) 43 (9%) 35 (73%) 2

21 Responses Response Category Evaluable Patients (N=45) Double refractory N=32 High risk cytogenetics N=27 Overall response no. (%) 29 (65) 22 (68) 15 (56) Best response no. (%) scr 3 (7) 1 (3) 2 (7) CR 1 (2) 1 (3) 1 (4) VGPR 9 (2) 6 (18) 1 (4) PR 16 (36) 14 (44) 11 (41) Isatuximab Pts received prophylaxis against infusion reactions prior to treatment* IARs reported in 9/2 pts (45%); all Gr 1/2 severity IARs occurred predominantly during the first infusion IAR after first infusion in three pts; one IAR after 18th infusion No treatment discontinuations due to IARs Initial infusion rate: 87.5 mg/h (5 mg/kg); 175 mg/h (1 and 2 mg/kg) Median infusion duration, hrs First infusion: 4.4 (1 mg/kg), 4.7 (2 mg/kg) Subsequent infusions: 2.6 (1 mg/kg), 4.6 (2 mg/kg) Patients (%) IARs by infusion and dose Grade 1 Grade 2 1 st >1 1 st >1 1 st >1 (n=8) (n=8) (n=6) (n=6) (n=6) (n=6) 5 mg/kg 1 mg/kg 2 mg/kg Isatuximab dose Data cut-off August 15, 216. *Diphenhydramine 5 mg IV (or equivalent), ranitidine 5 mg IV (or equivalent), and acetaminophen 65 1 mg orally Richardson P et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP

22 Response Summary 1 PR VGPR CR 8 ORR (%) % % 64.% QW/Q2W (n=8) 1 QW/Q2W (n=6) All patients (n=14) Among IMiD-refractory pts, the confirmed ORR was 64% (7/11) Three pts with high-risk cytogenetics (del17p or t[4:14]): one attained VGPR and another minimal response (MR) Data cut-off August 15, 216. a Efficacy data for the 2 mg/kg cohort are not yet mature. CR, complete response; ORR, overall response rate; PR, partial response; VGPR, very good partial response Richardson P et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-27. Baseline Demographics and Clinical Characteristics Characteristic DARA + POM-D N=13 Age, y Median (range) 64 (35-86) Cytogenetic profile, n (%)* Standard risk High risk del17p t(4;14) t(14;16) n=87 65 (75) 22 (25) 16 (18) 6 (7) 1 (1) DARA + POM-D Characteristic N=13 Prior lines of therapy, n (%) Median (range) 4 (1-13) >3 53 (52) Prior ASCT, n (%) 76 (74) Prior PI, n (%) Prior BORT Prior CARF 12 (99) 11 (98) 34 (33) Prior LEN, n (%) 13 (1) Prior PI + IMiD, n (%) 12 (99) Refractory to, n (%) LEN BORT CARF 92 (89) 73 (71) 31 (3) Refractory to PI + IMiD, n (%) 73 (71) ISS, International Staging System; ASCT, autologous stem cell transplant; PI, proteasome inhibitor; BORT, bortezomib; CARF, carfilzomib; LEN, lenalidomide; IMiD, immunomodulatory drug. *Based on FISH or karyotyping. Percentages based on n=87 as denominator. Chari A et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP

23 Responses ORR (scr+cr+vgpr+pr) Best response scr CR VGPR PR MR SD PD NE VGPR or better (scr+cr+vgpr) DARA + POM-D (N=13) n (%) 95% CI 62 (6) (8) 9 (9) 26 (25) 19 (18) 2 (2) 26 (25) 3(3) 1 (1) (42) CR or better (scr+cr) 17 (17) ORR, % % CR or better PR VGPR CR scr ORR = 6% DARA + POM-D (N = 13) 42% VGPR or better Deep responses were observed with DARA + POM-D Chari A et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-24. Venetoclax 23

24 BCL2 Proteins Regulate Cell Survival BCL2 Cellular Stress Examples include: Most Cancer Therapies Becoming Cancer Apoptosis (a mechanism by which cells die) BCL2 Proteins Regulate Cell Survival Venetoclax BCL2 Cellular Stress Examples include: Most Cancer Therapies Becoming Cancer Apoptosis (a mechanism by which cells die) 24

25 Types of Initial Therapy Percentage of patients (n=124) 36.8 (n=49) 29.9 (n=179) 42.6 (n=156) 39.8 (n=53) 48.2 (n=289) p= (n=26) 14.9 (n=54) (n=89) 8.2 (n=3) 3.8 (n=5) 7. (n=42). PI-based IMiD-based PI+IMiD-based Others t(11;14) Non-t(11;14) translocations No translocation Kumar S et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-45. Survival No translocation t(11;14) Non-t(11;14) translocation PFS, median (95% CI) P value OS, median (95% CI) P value No translocation (n=599) 28.3 ( ) 13.6 ( ) t(11;14) (n=366) 23. ( ) < ( ) <.1 Non-t(11;14) translocation (n=133) 19. ( ) 49.8 ( ) Kumar S et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP

26 Single-Agent Venetoclax 5 scr CR VGPR PR Percentage of Patients ORR 21% 3% 4% 8% 6% All Patients N=66 ORR 4% 4% 1% 13% 13% t(11;14) n=3 ORR 6% 3% 3% non-t(11;14) n=36 Data cutoff of 19Aug216 Kumar S et al. Presented at the 16 th International Myeloma Workshop, March 1-4, 217. Abstract OP-45. There Are Several BCL2 Proteins That Block Apoptosis Venetoclax Cellular Stress Examples include: Most Cancer Therapies Becoming Cancer MCL1 BCLX BCL2 A M G Apoptosis (a mechanism by which cells die) 26

27 New Immune Therapies New Immune Therapies in Myeloma CAR T-cells Bi-specifics Myeloma targets for both CAR T-cells and Bispecifics include: BCMA and SLAMF7 27

28 Questions & Answers Closing 28

29 Resources for ou! MMRF nurse specialist Have questions about the trials or information you heard today? Call our MMRF nurse specialists. An MMRF nurse specialist can guide you through your multiple myeloma journey every step of the way. Call Monday Friday, 9 7 ET Call now MMCT(6628) MMRF CoMMunity Gateway Accelerator Magazine Knowledge. Resources. Research. Community. Join our trusted multiple myeloma community! Continue the conversation with other patients, caregivers, and experts! Join today 29

30 Upcoming MMRF Webinars Summer 217 Series Topic Date Time Immunotherapy Meeting Highlights Monoclonal antibodies June 14, 217 1: PM ET Vaccines July 217 1: PM ET Engineered Immune Cells August 9, 217 1: PM ET American Society of Clinical Oncology and the European Hematology Association July 217 1: PM ET For more information or to register, visit: themmrf.org MMRF Multiple Myeloma Summits Fall 217 Saturday, September 16, 217 Chicago, Illinois Andrzej Jakubowiak, MD Chair University of Chicago Medical Center Saturday, October 14, 217 Charlotte, North Carolina Saad Z. Usmani, MD Chair Friday, November 3, 217 New ork City, New ork Sundar Jagannath, MD Chair The Mount Sinai Medical Center Tisch Cancer Institute Mount Sinai School of Medicine Levine Cancer Institute Saturday, November 18, 217 Los Angeles, California James Berenson, MD Co-Chair Institute for Myeloma and Bone Cancer Research Amrita. Krishnan, MD Co-Chair Judy and Bernard Briskin Center for Multiple Myeloma Research City of Hope Medical Center To register, please visit: themmrf.org/patient 3