Top Myeloma Research Presented at ASH 2022
Thank you to our sponsors!
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Topics to be covered • Bispecific antibodies • CAR T Frontline • Iceland Screening: iSTOPMM • ASCENT & CESAR TRIALS • MRD Testing: Ultra sensitive / Mass Spectrometry • Dex Sparing combination 3
• Dr. Durie blog: “Top Abstracts of Interest at the ASH 2022 Myeloma Sessions” dated December 14, 2022
https://www.myeloma.org/blog/top-myeloma-abstracts-ASH2022?utm_medium=email&utm_source=engagingnetworks&utm_campaign=myeloma-minute-email-12-1522&utm_content=Myeloma+Minute+12-15-22+D1
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https://www.myeloma.org/videos/conversation-myeloma-experts-making-sense-evolving-treatment-landscape
• IMWG Conference Series at ASH 2022: https://www.myeloma.org/videos/imwg-conference-series-ash-2022
Resources:
IMF Support Group Leaders’ Perspective / Blogs: https://ash2022blogs.myeloma.org
IMF Symposium: “A Conversation with the Myeloma Experts: Making Sense of the Evolving Treatment Landscape”
Building Dietary Evidence for Hematologic Malignancies – Mechanistic Insights
• ASH 2022 Abstract Summaries: https://ash.myeloma.org •
https://annualmeeting.hematology.org/live-stream/37816337/Building-Dietary-Evidence-for-Hematologic-Malignancies--Mechanistic-Insights
Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1 Ajai Chari, Cyrille Touzeau, Carolina Schinke, Monique C. Minnema, MD, PhD, Jesus Berdeja, MD, Albert Oriol, Niels WCJ Van De Donk, MD, Paula Rodriguez Otero, Elham Askari, Maria-Victoria Mateos, MD, Luciano J. Megala Costa, MD, PhD, Jo Caers, PhD, Leo Rasche, MD, Amrita Y. Krishnan, MD, FACP, Deeksha Vishwamitra*, Xuewen Ma, Xiang Qin, Katharine S. Gries, PhD, PharmD, Michela Campagna, Tara Masterson, Brandi Hilder, Jaszianne Tolbert, Thomas Renaud, Jenna D. Goldberg, Christoph Heuck, Jesús San-Miguel, MD, PhD and Philippe Moreau, MD 5 Abstract 157
Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA;
Sarah Cannon Research Institute, Nashville, TN, USA; 6Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias I Pujol, Badalona, Barcelona, Spain; 7Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; 8University of Navarra, Pamplona, Spain; 9Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; 10University Hospital of Salamanca/IBSAL/CIC/CIBERONC, Salamanca, Spain; 11University of Alabama at Birmingham, Birmingham, AL, USA; 12University of Liège, Liège, Belgium; 13University Hospital of Würzburg, Würzburg, Germany; 14City of Hope Comprehensive Cancer Center, Duarte, CA, USA; 15Janssen Research & Development, Spring House, PA, USA; 16Janssen Global Services, Raritan, NJ, USA; 17Janssen-Cilag, Madrid, Spain; 18Janssen Research & Development, Raritan, NJ, USA; 19University Hospital Hotel-Dieu, Nantes, France
University Medical Center Utrecht, Utrecht, Netherlands;
Presented at the 64th American Society of Hematology (ASH) Annual Meeting; December 10–13, 2022; New Orleans, LA, USA.
https://www.congresshub.com/Oncology/ ASH2022/Talquetamab/Chari
The QR code is intended to provide scientific information for individual reference, and the information should not be altered or reproduced in any way. Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D × CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma: Phase 1/2 Results From MonumenTAL-1 Ajai Chari1, Cyrille Touzeau2, Carolina Schinke3, Monique C Minnema4, Jesus G Berdeja5 , Albert Oriol6, Niels WCJ van de Donk7, Paula Rodriguez-Otero8, Elham Askari9, María-Victoria Mateos10 , Luciano J Costa11, Jo Caers12, Leo Rasche13, Amrita Krishnan14, Deeksha Vishwamitra15, Xuewen Ma15, Xiang Qin15, Katharine S Gries16, Michela Campagna17, Tara Masterson15 , Brandi Hilder15, Jaszianne Tolbert15, Thomas Renaud18, Jenna D Goldberg18, Christoph Heuck15 , Jesús San-Miguel8, Philippe Moreau19 1Mount Sinai School of Medicine, New York, NY, USA; 2Centre Hospitalier Universitaire de Nantes, Nantes, France;
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Talquetamab: T-Cell Bispecific Antibody Targeting the Novel Antigen Target GPRC5D • Talquetamab is a novel first-in-class, off-the-shelf, Tcell redirecting bispecific antibody directed against a new antigen target called GPRC5D1,2 • GPRC5D is a novel antigen target in myeloma that is highly expressed on malignant plasma cells with limited expression in normal human tissues,3-6 including hematopoietic stem cells7 • Talquetamab has shown an ORR of 64–70% with QW and Q2W dosing in the MonumenTAL-1 study (NCT03399799/NCT04634552)8 • Updated results from the MonumenTAL-1 study are presented, including all patients treated at each RP2D for the first time, as well as a cohort of patients with prior CAR-T cell or bispecific antibody treatment Talquetamab GPRC5DxCD3 antibody GPRC5 D T-cell activation Cytokine release Perforin/granzymes T cell CD3 Myeloma cell Myeloma cell death 7
MonumenTAL-1: Overall Response Rate and Duration of Response ORRa 14.7% 15.9% 25.9% 24.8% 9.8% 12.4% 23.8% 20.0% 0 20 40 60 80 100 PR VGPR CR sCR 74.1% (106/143) 73.1% (106/145) ≥VGP R: 59.4% 0.4 mg/kg SC QW 0.8 mg/kg SC Q2W Patients (%) ≥VGP R: 57.2% 100% 80% 60% 40% 20% 0%
DOR,
SC
100%
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100% 80% 60% 40% 20% 0% 0 3 6 9 12 15 Duration of response, mo 18 21 106 82 51 16 6 4 1 0 47 44 32 14 5 4 1 0 Patients at risk % of patients
0.8 mg/kg
Q2W mDOR: 13.0 (10.6–NE) mDOR: NE (10.6–NE) All responders ≥ CR % of patients
80% 60% 40% 20% 0% 0 3 6 9 12 15 Duration of response, mo 18 21 24 27 30 106 87 67 50 39 8 7 5 2 1 0 48 47 45 39 34 7 6 5 2 1 0 Patients at risk DOR, 0.4 mg/kg SC QW mDOR: 9.3 (6.6–12.7) mDOR: NE (20.2–NE) All responders ≥ CR • ORR was consistent across subgroups including baseline ISS-III score, baseline cytogenetic risk, number of prior therapies, refractoriness to prior therapy, and belantamab exposure, except among patients with baseline plasmacytomas • Treatment at both doses led to durable responses • Median DOR not reached for those patients who achieved ≥CR mPFS: 7.5 months (95% CI: 5.7–9.4; 33% censored) mPFS: 11.9 months (95% CI: 8.4–NE; 61% censored)
Talquetamab and MonumenTAL-1: Conclusions • Talquetamab, a novel agent directed against a new antigen target in myeloma, demonstrated an ORR of 73–74% with QW and Q2W schedules in a heavily pretreated group of patients – In those with prior T-cell redirection therapy, a 63% ORR was observed – Safety and PK/PD activity were consistent between QW and Q2W dosing schedules • Median DOR was ≥9 months in all groups, with longer DOR in those achieving ≥CR • Overall, a low rate of discontinuations due to AEs was observed; the most common AEs included CRS, skin-related events, nail-related events, and dysgeusia • An ongoing phase 3 study (NCT05455320) is evaluating talquetamab vs approved therapies; additional phase 1 studies (NCT04586426; NCT04108195; NCT05050097; NCT05338775) are evaluating combination with other agents, including teclistamab, daratumumab, IMiDs, and/or a PD-1 inhibitor >70% ORR with talquetamab in patients with heavily pretreated myeloma 9
ASH 2022: Bispecific Antibodies in RR MM Drug Target Median prior lines, n ORR, % CRS, % Neurotox, % Infection % All; G3/4 Step-up/ Notes ABBV-3832 (n = 58, 6) BCMA 4-5 (3-12) 60% @ 60mg (n = 58) 83% @ 40mg (n=6) 72-83% (Gr3; 0-2%) [5%] 43-50 % No/ IV Q3W REGN-54583 (n = 167) BCMA 6 75% @≥200 (n=24) 41% @ <200 (n=49) 47.9% (Gr3 0.3%) 4% 52; 22 % Yes-02, IV Dosing; Qwk=>Q2wk Elranatamab 1 (n=55) BCMA 5 (2-14) 64% @highest doses (n = 55) 67% (Gr 1-2) 3.8% Mag-1 SC: recover DAY1 Elranatamab 4 (n = 123) BCMA 5 (2-22) 61% @ 12-33-76 mg SC QWk 56.3% @RP2D (0.6% Gr3) 3.4% 68.1% Mag – 3 Yes-2; SC QW dosing! Alnuctamab5 (n=47, SC) BCMA 4 51% @ 10, 15, 30, 60 mg (n=41) 53% with SC (Gr 1-2: 48% Toci) 2% (Gr 1) NR 2 step ups: SC: QW, Q2W, Q4W Talquetamab 6 (n = 141 QW, 143 Q2W SC) GPRC5 D 5 (2-13) 5 (2-17) 74.0% @ RP2D 73.1% 79% 72.4 % 3% Gr3 @RP2D) 7% @RP2D (4.9% all SC) Yes-3; SC dosing! Some Gr3 skin rash, oral tox Cevostamab7 (n = 28) FcRH5 4 (2-7) 50% 36% (2% G3) 28% 1. Raje. ASH 2022. Abstr 157. 2. Voorhees. ASH 2022. Abstr 1919. 3. Bumma. ASH 2022 Abstr. 4555 4. Bahlis N, et al. ASH 2022 Abstr 158. 5. Wong ASH 2022 Abstract 162. 6. Chari. ASH 2022. Abstr 292. 7. Trudel ASH 2022 Abstr 567 10
Panel Discussion
CARs in RR MM 1. Usmani ASH 2022. Abstr 361. 2. Dhodapkar ASH 2022. Abstr 3314. 3. Kumar. ASH 2020. Abstr 133. 4. Costello. ASH 2020. Abstr 134. 5. Alsina. ASH 2020. Abstr 130. 6. Mailankody. ASH 2020. Abstr 129. Now FDA approved! Agent Trial Median prior lines of Tx, n Special features ORR, % CRS, % NT, % Survival Notes Idecabtagene vicleucel Phase II KarMMa-2a1 KarMMa-2c2 1 Fxnl HR, early relapse 83 (n=37) 87.1 (n=31) 84 56.1 % 21.8% (G1-2) NR mPFS: 11.4 mo NR (150-450x106 ) Ciltacabtagen e autoleucel -CohortC CARTITUDE12 6 BCMA -FasTCAR Abstract 366 Phase I (n=13) 5 BCMA/CD19 dual 100% 90 (3% Gr3) -Real World Ide-cel Retro (n=50) 9 70 16 ALLO-715 CAR-T + ALLO647 anti-CD52 mAb Phase I UNIVERSAL6 5 AlloCAR T-cell product 74% 45 0 mPFS=3.2 m Variability in LD, Tx ≤5 days of enrollment!! No GVHD 12
Juan Du, Weijun Fu, Jing Lu, Wanting Qiang, Haiyan He, Jin Liu, Ying Yang, Zhongyuan Feng, Lina Jin, Xiaoqiang Fan, Jia Liu, Qi Zhang, Lianjun Shen, Lihong Weng and Wei Cao Abstract 366 13 Phase I Open-Label Single-Arm Study of BCMA/CD19 Dual-Targeting FasTCAR-T Cells (GC012F) as First-Line Therapy for Transplant-Eligible Newly Diagnosed HighRisk Multiple Myeloma
Targeting BCMA/CD19 is designed to drive fast, deep and durable responses in multiple myeloma (MM) patients § BCMA is universally expressed on malignant plasma cells1 § CD19 is expressed on both multiple myeloma cells and their progenitors2, making it a valid therapeutic target to treat multiple myeloma 1. Tai YT, Anderson KC. Immunotherapy. 2015;7(11):1187-1199. 2. Boucher K, Parquet N, Widen R, et al. Clin Cancer Res. 2012;18(22):6155-6168. GC012F: Introduction _________________ BCMA-CD19 Dual CAR-T anti-CD19 scFv anti-BCMA scFv CD19 BCMA MM Progenitor MM cell CD19 (Low expression) 14
GC012F: FasTCAR Cuts Manufacturing Time to 22-36 Hours Combines Activation & Transduction Steps, and Eliminates Need for ex vivo Expansion ex vivo Expansion 5 days to 5 weeks Activation Transduction 1 to 3 days 1 to 2 days Conventional Manufacturing 1 to 6 WEEKS Concurrent Activation-Transduction 22 - 36 HOURS Releasing Tests Purification Filling Freezing Release & Infusion Apheresis Isolation Apheresis Isolation Releasing Tests Purification Filling Freezing Release & Infusion Designed to address major challenges faced by conventional autologous CAR-T Key advantages: • Faster to patient • Enhanced T-cell quality 15
6 17 12 20 82 100 83 80 0 20 40 60 80 100 Patients(%) ORR 100% ORR 100% ORR 100% ORR 100% All patients (N=17) DL1 (n=1) DL2 (n=6) DL3 (n=10) § ORR = 100% (17/17) patients § Best response achieved to date § 82% (14/17) MRD- sCR § 94% (16/17) VGPR or better § Median duration of response (DOR) was not reached at data cut off § Median duration of follow up 8.1 months (range: 1.3 - 15.4 months) GC012F: Efficacy Assessment – ORR PR VGPR CR/sCR ORR at time of data cut off Oct 14th 2022 16
§ GC012F shows a favorable safety profile in newly diagnosed multiple myeloma patients o Only 29% (5/17) patients experienced Grade 1-2 CRS o No Grade ≥3 CRS and no ICANS or any neurotoxicity observed § 100% (17/17) ORR in high risk population o 82% sCR, 94% ≥VGPR o Patients continue being followed up for deepening and durable response § 100% (17/17) MRD negativity § FAST and DEEP responses with median DOR not reached § GC012F BCMA/CD19 dual-targeting CAR-T cell therapy shows very encouraging anti-tumor activity in transplant-eligible, high risk, newly diagnosed multiple myeloma patients GC012F: Conclusions ______________________ 17
Panel Discussion
Predicting the Need for Upfront Bone Marrow Sampling in Individuals with MGUS
Derivation of a Multivariable Prediction Model Using the
Elias Eythorsson , Saemundur Rognvaldsson , Sigrun Thorsteinsdottir , Elin Ruth Reed , Guðrun Asta Sigurdardottir2 , Brynjar Vidarsson1, Pall Torfi Onundarson1,2, Bjarni A. Agnarsson1,2, Margret Sigurdardottir1 , Isleifur Olafsson1 , Ingunn Thorsteinsdottir1, Signy Vala Sveinsdottir1 , Fridbjorn Sigurdsson1 , Asdis Rosa Þordardottir2 , Runolfur Palsson1,2, Olafur Skuli Indridason1,2 , Thorir Einarsson Long2,4 , Asbjorn Jonsson5 , Gauti Kjartan Gislason2, Andri Olafsson2, Jon Sigurdsson2 , Hlif Steingrimsdottir1 , Malin Hultcrantz6, Brian G. M. Durie7, Stephen Harding8, Ola Landgren9, Thor Aspelund10 , Thorvardur Jon Love2 , Sigurdur Yngvi Kristinsson1,2
1Landspítali – The National University Hospital of Iceland, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Dept of Hematology, Rigshospitalet, Copenhagen, Denmark. 4Skåne University Hospital, Lund, Sweden. 5Akureyri Hospital, Akureyri, Iceland. 6Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 7Cedar-Sinai Samual Oschin Cancer Center, Los Angeles, CA, USA. 8The Binding Site, Birmingham, West Midlands, UK. 9Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA. 10Center for Public Health Sciences, University of Iceland, Reykjavik, Iceland.
Email: elias.eythorsson@gmail.com, Twitter: @eliaseythorsson
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iStopMM study cohort: 75,422 persons ≥40 years of age (51% of the Icelandic population) were screened, 3,358 MGUS cases identified, of which 2,542 were randomized to active follow-up
Sæmundur Rögnvaldsson et al., ‘Iceland Screens, Treats, or Prevents Multiple Myeloma (IStopMM): A Population-Based Screening Study for Monoclonal Gammopathy of Undetermined Significance and Randomized Controlled Trial of Follow-up Strategies’, Blood Cancer Journal 11, no. 5 (17 May 2021): 1–13, https://doi.org/10.1038/s41408-021-00480-
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• Multivariable proportionalodds logistic model was derived on 1,013 persons with IgG, IgA or biclonal MGUS • Outcome was the highest %BMPC on smear or trephine biopsy: 0-4%, 5-9%, 10-14%, and ≥15% • Predictors: isotype, M protein, FLC ratio, and total IgG, IgA, and IgM 21
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Mayo Clinic Risk Stratification: Low Our predicted risk: 3.7%
Agreement
https://istopmm.com/riskmodel/
• This study provides an evidence-based approach to selecting persons with MGUS in whom BM sampling may be deferred • Represents a shift from a group-based approach to a riskbased approach • Consistently outperforms other approaches of deciding whether to obtain BM sample • Will need to be externally validated in other screened and clinical cohorts 24
Panel Discussion
Fixed Duration Therapy With Daratumumab, Carfilzomib, Lenalidomide And Dexamethasone For High-Risk Smoldering Multiple Myeloma- Results Of The ASCENT Trial
Abstract #757 26
Shaji Kumar, Melissa Alsina, Betsy LaPlant, Ashraf Badros, Al-Ola Abdallah, Rafat Abanour, Erik Asmus, Binod Dhakal, Cara Rosenbaum, Daniel Egan, Manisha Bhutani, Andrzej Jakubowiak, Brian Durie
Selection criteria and End Points • Patients with SMM with high-risk disease1 – defined by the IMWG updated risk stratification criteria- presence of any two of the following: Serum M spike > 2 gm/dL OR an involved to uninvolved FLC ratio > 20 OR bone marrow PC% > 20%) – OR a score of ≥9 using the risk scoring system using FLC ratio, serum M spike, marrow plasma cell % and presence of high-risk FISH • Primary endpoint of the trial is the rate of confirmed sCR • Progression included biochemical progression as well as development of symptomatic MM 1Mateos, MV., Kumar, S., et al. Blood Cancer J. 10, 102 (2020) 27
Treatment INDUCTION (4-week cycles for 6 cycles) • Carfilzomib (36 mg/m2 twice weekly or 56mg/m2 weekly) • Lenalidomide (25 mg daily for three weeks) • Daratumumab (weekly for 8, every other week for 16 weeks) • Dexamethasone 40 mg weekly CONSOLIDATION (4-week cycles for 6 cycles) • Carfilzomib (36 mg/m2 twice weekly or 56mg/m2 weekly) • Lenalidomide (25 mg daily for three weeks) • Daratumumab (every 4 weeks) • Dexamethasone 20 mg weekly MAINTENANCE (4-week cycles for 12 cycles) • Lenalidomide (10 mg daily for 3 weeks) • Daratumumab (q 8 weeks) 28
Response • The best overall response rate was 97% (94% ≥VGPR) • Seventy-three (84%) patients became marrow MRDneg – 53 [61%] also in CR – IMWG MRDneg • Median time to MRD negativity of 6.6 months; 53 at end of induction, 16 at end of consolidation and 4 at end of maintenance. 38 26 30 2 1 2 Response Rate sCR CR VGPR PR SD NE 29
Progression Free Survival
• Three patients have progressed, median PFS for the cohort has not been reached; PFS rate (95%CI) at 3 years was 89.9% (82.3-98.3%)
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Conclusions • The quadruplet regimen is effective in this high-risk smoldering patient population • Toxicities seen were similar to that seen with the same regimen as used in active myeloma • No new toxicity signal was observed • Patients continue treatment/ observation post completion of 2 years of therapy, with the majority still in deep response • Longer term outcome, especially with sustained MRD negativity, will require further follow up • We anticipate a fraction of patients will be “cured” 31
GEM-CESAR (Efficacy on ITT; N=90) Response category Induction (n=90) HDT-ASCT (n=90) Consolidatio n (n=90) Maintenance (n=90) ORR, n(%) 85 (94%) 82 (91%) 85 (94%) 80 (95%) ³CR 37 (41%) 54 (60%) 64 (70%) 57 (63%) VGPR 35 (39%) 17 (19%) 14 (16%) 9 (10%) PR 13 (14%) 11 (12%) 7 (8%) 3 (3%) SD 1 (1) 1 (1) -Progressive disease 2 (3%)* - - 7 (7%)** Not evaluable 2 (3%) 7(8%) 5 (5%) *Progressions were biochemical **Progressions were biochemical progressions in the 7 patients and 1 pt progressed to active disease during maintenance 32
GEM-CESAR : Survival Outcomes
Median follow-up: 70.1 (6.2-88.8) months
TTP to active MM
Overall survival
TTP at 70 months: 94%
Number of patients at risk
90 88 86 85 83 82 80 41 10 0
5 pts progressed to symptomatic disease and in 4 pts, the progression was first asymptomatic
7 pts have died: 3 disease-related; 1 cardiac arrest not treatment-related; 1 ischemic stroke during induction; 1 lung cancer; 1 MDS
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Panel Discussion
vs QIP-MS to assess Minimal
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Clinical Impact of NGF
Residual Disease in NDMM Patients Receiving Maintenance in the GEM2014MAIN Trial Noemí Puig, Cristina Agulló, Teresa Contreras, Bruno Paiva, María-Teresa Cedena, Laura Rosiñol, Ramón García-Sanz, Joaquín Martínez-López, Albert Oriol, María-Jesús Blanchard, Rafael Ríos, Jesús Martín, Anna Sureda, Miguel-Teodoro Hernández, Javier de la Rubia, José-María Moraleda, Felipe de Arriba, Luis Palomera, María-Belén Iñigo, Joan Bargay, Joan Bladé, Jesús F San Miguel, Juan-José Lahuerta and María-Victoria Mateos On behalf of the Myeloma Spanish Group (GEM/PETHEMA)
GEM2012 MENOS65 R MRD in BM by NGF positive negative Rd Observation 316 NDTE MM patients enrolled in the GEM2012 and achieving at least stable disease at the end of treatment RD Ixa-RD year 1 year 2 year 3 year 4 year 5 R: lenalidomide 15mg po od days 1-21 of each 28 days cycle, D: dexamethasone 20mg po od days 1-4 and 9-12, Ixa: 4mg po od days 1, 8 and 15, d: 20mg po od days 1-4 GEM2014MAIN Phase III, multicenter, open-label randomized trial NGF following the Euroflow guidelines (sensitivity >10-5) M-protein in serum by SPEP/sIFE and QIP-MS (GAMKL) MRD in BM by NGF ³ SD post-consolidation QIP-MS performed with EXENTTM (Binding Site, in development) using IgG/A/M, total kappa and total lambda specific beads 36
% of patients with detectable disease NGF QIP-MS (GAMKL) IFE 0 10 20 30 40 11% (n=17) 24% (n=37 ) 29% (n=45 ) 37
Ability to identify the presence of residual disease during maintenance
IFE QIP-MS (GAMKL)
Progression-free survival according to the results of the three methods 0 1 2 3 4 5 6 0 20 40 60 80 100 Survival proportions: Survival of M2 IFE Time (years) % P F S p=0.8396 0 1 2 3 4 5 6 0 20 40 60 80 100 Survival proportions: Survival of M2 NGF Time (years) % P F S NGF + NGFmPFS: 3.2 years p<0.0001 mPFS: NR HR: 0.21 95% CI, 0.10−0.44
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NGF IFEpos IFEneg MSpos MSneg NGFpos NGFneg 0 1 2 3 4 5 6 0 20 40 60 80 100 Survival proportions: Survival of M2 GAMKL-MS Time (years) % P F S GAMKL-MS + GAMKL-MSp=0.0011 HR: 0.37 95% CI, 0.17−0.80 mPFS: NR mPFS: NR
100
80
% P F S
60
MRDneg MRDneg
40
MS (GAMKL)
% P F S
20
NGF mPFS=4.3 y
mPFS=NR 0 2 4 6 8 0
100
PC NGF (n=175) Time (years)
80
60
40
20
mPFS=4.43 y QIP
NGF + NGF -
100
80
% P F S
60
40
mPFS: NR HR: 0.19 95% CI, 0.08−0.41
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00/10 11/01 mPFS: 2.9 years p<0.0001
Survival proportions: Survival of PC-M2 sustained MRD NGF Time (years)
0 1 2 3 4 5 6 0
100
GAMKL+ GAMKL -
mPFS=NR p=0.0059
(n=57) HR: 0.53 95% CI, 0.32-0.88
% P F S
80
60
(n=76) HR: 0.39 95% CI, 0.24-0.63 p<0.0001 0 1 2 3 4 5 6 0
mPFS: NR mPFS: NR 0 2 4 6 8 0
40
20
00/10 11/01 p=0.0013 HR: 0.36 95% CI, 0.16−0.81
Survival proportions: Survival of PC-M2 sustained MRD GAMKL Time (years)
Survival proportions: Survival of PC GAMKL soft (n=175) Time (years)
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The added clinical value of sustained MRD negativity Sustained
Ultra-Sensitive Assessment of
Measurable Residual Disease (MRD) in Peripheral Blood (PB) of Multiple
Myeloma (MM) Patients Using Bloodflow
Laura Notarfranchi, Anastasiia Zherniakova, Marta Lasa, PhD, Noemi Puig, MD, PhD, María Teresa Cedena, MD, PhD, Joaquin Martinez-Lopez, MD PhD,, María José Calasanz, PhD, Diego Alignani, PhD, Leire Burgos, Irene Manrique, Yi-Ju Huang, Jochen Fracowiak, Clara Gomez,, Felipe De Arriba, PhD, Paula Rodríguez-Otero, MD, PhD, Luis Palomera, MD, PhD, Anna Sureda, Maria Esther Clavero Sanchez, Miguel Angel Alvarez, Angela Ibanez Garcia, Miguel-Teodoro Hernández, MD, PhD, Albert Perez, Ana Pilar Gonzalez, PhD, Enrique M. Ocio, Juan Flores-Montero, Alberto Orfao, MD, PhD, Juan Jose Lahuerta, MD, PhD, María-Victoria Mateos, MD, PhD, Laura Rosiñol, MD, PhD, Joan Bladé Creixenti, MD, PhD, Jesús San-Miguel, MD, PhD and Bruno Paiva
40 Abstract 865
Background Assessing MRD in bone marrow (BM) using next-generation flow (NGF) or sequencing precludes periodic evaluations because of its invasiveness. MRD assessment in PB could overcome this limitation, but its clinical value is not established and the negative predictive value (NPV) when compared to BM is <70%. This is because tumor burden in PB is ~3log lower than in BM, and methods capable of detecting MRD below 10-6 are thus needed for improved concordance. We first aimed at investigating the prognostic value of MRD assessment in PB using NGF. Our second aim was to develop a new method with increased sensitivity. 41
NEW Blood Flow Test
(CD138, CD269, CD229, CD317, CD319)
enrichment NGS of cfDNA (VDJ & mutations) – H12O Mass spectrometry - HUS
A new universally applicable and ultra-sensitive test to monitor MRD in PB NGF detection of CTCs
Before
MRD assessment in PB using NGF was prognostic in pts under maintenance or observation. Notwithstanding, a new method (BloodFlow) was developed to increase the NPV and showed an unprecedented sensitivity to detect MRD down to 10-8 in PB. BloodFlow detected MRD in PB more frequently than NGF, with a consequent decrease in the number of cases with persistent MRD in BM while undetectable in PB, which were more frequent during early and intensive treatment stages. These results suggest the possibility of periodic and ultra-sensitive MRD assessment in PB during maintenance/observation.
Conclusion
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Panel Discussion
A Dexamethasone Sparing-Regimen with Daratumumab and Lenalidomide in Frail Patients with Newly-Diagnosed Multiple Myeloma: Efficacy and Safety Analysis of the Phase 3 IFM2017-03 Trial Manier, J. Corre, C. Hulin, K. Laribi, C. Araujo, G.M. Pica, C. Touzeau, P. Godmer, B. Slama, L. Karlin, F. Orsini Piocelle, M. Dib, M. Macro, L. Sanhes, A. Perrot, J.Y. Mary, J. Lambert, H. Avet-Loiseau, P. Moreau, X. Leleu, T. Facon 45 Abstract 569
2017-03 - Study design Randomization stratified by ISS (I vs II vs III) and age (<80 vs ≥80) In Arm B low-dose dex (20mg/week) during Cycle 1 and 2 (with SC dara) Primary endpoint: PFS Interim analysis endpoints: 12-months-therapy data cut: • overall response rate, • VGPR or better rate, • MRD rate • occurrence of grade 3 or more side effects NCT03993912 46
IFM
IFM 2017-03 – Response and MRD rates
Best response VGPR or better over time MRD at 10-5 by NGS, in ITT analysis
Best overall response rate was significantly higher with DR and deeper responses were obtained with DR at all time points, including at early time points. DR improved rates of MRD negativity vs. Rd
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IFM 2017-03 – Conclusions Ø IFM2017-03 is the first randomized phase 3 trial dedicated to frail patients Ø Daratumumab-lenalidomide was superior to lenalidomide-dexamethasone for ORR, rates of VGPR or better and rates of MRD negativity, and rapid responses were obtained Ø Safety profile was favorable without increased infection or pneumonia rates with DR vs. Rd and with similar rates of treatment discontinuation Ø This preliminary data on a dexamethasone-sparing regimen for frail patients is encouraging Ø The PFS analysis is ongoing We acknowledge all IFM centers and the patients and their family who participated to the trial 48
Panel Discussion
Thank you to our sponsors!
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We Want to Hear From You!
Feedback Survey
At the close of the meeting a feedback survey will pop up. Click “continue” to complete the survey.
This will also be emailed to you shortly after the workshop.
Please take a moment to complete this survey.
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