GEM2005MAS65 Trial: Bortezomib-Based Maintenance Increases CR Rate and PFS in Elderly Patients With Newly Diagnosed Multiple Myeloma Slideset on: Mateos.

Slides:

Advertisements

Similar presentations

Palumbo A et al. Proc ASH 2013;Abstract 536.

Advertisements

Facon T et al. Proc ASH 2013;Abstract 2.

Should Alkylators be used Upfront in Transplant-Ineligible Patients? NO!! Lymphoma-Myeloma October 2013 Scottsdale, Arizona Rochester, Minnesota Jacksonville,

Update on transplant-ineligible patients: Which regimens are best?

Ravi Vij MD Associate Professor Section of BMT and Leukemia

Efficacy and Safety of Three Bortezomib-Based Combinations in Elderly, Newly Diagnosed Multiple Myeloma Patients: Results from All Randomized Patients.

1. 2 Lenalidomide in Newly Diagnosed Multiple Myeloma Clinical Update EHA 2010 DR. OUSSAMA JRADI.

Palumbo A et al. Proc ASH 2012;Abstract 446.

Effect of Age on Efficacy and Safety Outcomes in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Receiving Lenalidomide and Low-Dose Dexamethasone.

Treatment with Bendamustine- Bortezomib-Dexamethasone in Relapsed/Refractory Multiple Myeloma Shows Significant Activity and Is Well Tolerated Ludwig H.

Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) for Newly Diagnosed Multiple Myeloma (MM) Patients: Initial Results of a Multicenter, Open Label.

Palumbo A et al. Proc ASH 2014;Abstract 175.

A Phase II Study with Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) for Newly Diagnosed Multiple Myeloma Bringhen S et al. Proc ASH 2013;Abstract.

Bortezomib Induction and Maintenance Treatment Improves Survival in Patients with Newly Diagnosed Multiple Myeloma: Extended Follow-Up of the HOVON-65/GMMG-HD4.

Terapia nei pazienti non candidati

A Phase 3 Study Evaluating the Efficacy and Safety of Lenalidomide Combined with Melphalan and Prednisone Followed by Continuous Lenalidomide Maintenance.

Long Term Follow-up on the Treatment of High Risk Smoldering Myeloma with Lenalidomide plus Low Dose Dex (Rd) (Phase III Spanish Trial): Persistent Benefit.

Maintenance Therapy with Bortezomib plus Thalidomide (VT) or Bortezomib plus Prednisone (VP) in Elderly Myeloma Patients Included in the GEM2005MAS65 Spanish.

Continued Overall Survival Benefit After 5 Years’ Follow-Up with Bortezomib-Melphalan-Prednisone (VMP) versus Melphalan-Prednisone (MP) in Patients with.

Low Dose Decitabine Versus Best Supportive Care in Elderly Patients with Intermediate or High Risk MDS Not Eligible for Intensive Chemotherapy: Final Results.

Phase II Trial of R-CHOP plus Bortezomib Induction Therapy Followed by Bortezomib Maintenance for Previously Untreated Mantle Cell Lymphoma: SWOG 0601.

Mok TS, Wu SL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361: Gefitinib Superior.

Michel Attal, M.D., Valerie Lauwers-Cances, M.D., Gerald Marit, M.D., Denis Caillot, M.D., Philippe Moreau, M.D., Thierry Facon, M.D., Anne Marie Stoppa,

Slideset on: Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone.

Pomalidomide + Low-Dose Dexamethasone (POM + LoDex) vs High-Dose Dexamethasone (HiDex) in Relapsed/Refractory Multiple Myeloma (RRMM): MM-003 Analysis.

New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida TOURMALINE-MM1: Improved PFS With Ixazomib.

IFM Phase II Study: KRd Induction and Consolidation Before Len Maintenance Highly Effective in Newly Diagnosed MM New Findings in Hematology: Independent.

Phase II SAKK 35/10 Trial: Rituximab Plus Lenalidomide Shows Durable Activity in Untreated Follicular Lymphoma New Findings in Hematology: Independent.

Geisler C et al. Proc ASH 2011;Abstract 290.

MRD testing: which platforms, which patients?

Alessandra Gennari, MD PhD

Palumbo A et al. Proc ASH 2012;Abstract 200.

ELOQUENT-2: Elotuzumab + Len/Dex in R/R MM

Multiple Myeloma in the Non-transplant Setting

ASPEN: Prolonged PFS With Sunitinib vs Everolimus in Nonclear-Cell RCC CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* May 29 -

STAMPEDE: Docetaxel Significantly Improves Survival in Men With Hormone-Naive Prostate Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual.

Attal M et al. Proc ASH 2010;Abstract 310.

Korde N et al. Proc ASH 2012;Abstract 732.

Pomalidomide Plus Low-Dose Dex vs High-Dose Dex in Rel/Ref Myeloma

ELOQUENT-2: Addition of Elotuzumab to Len/Dex Extends PFS in Relapsed/Refractory Myeloma CCO Independent Conference Highlights of the 2015 ASCO Annual.

Maintenance Lapatinib After Chemotherapy in HER1/2-Positive Metastatic Bladder Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*

REMARC: Lenalidomide vs Placebo as Maintenance Therapy in Patients With DLBCL Following R-CHOP Induction New Findings in Hematology: Independent Conference.

IFM/DFCI 2009 Trial: Autologous Stem Cell Transplantation (ASCT) for Multiple Myeloma (MM) in the Era of New Drugs Phase III study of lenalidomide/bortezomib/dexamethasone.

FORTE: Induction With Carfilzomib, Dexamethasone, and Cyclophosphamide or Lenalidomide in Newly Diagnosed MM CCO Independent Conference Highlights* of.

Randomized, Open-Label Phase 1/2 Study of Pomalidomide Alone or in Combination with Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple.

Phase III EMN02/HO95 MM Trial: Upfront ASCT Prolongs PFS vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed MM CCO Independent Conference Coverage*

Slide set on: McCarthy PL, Owzar K, Hofmeister CC, et al

NCI/CTEP 7435: Eribulin Active, Tolerable in Urothelial Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* May 29 - June 2,

Vahdat L et al. Proc SABCS 2012;Abstract P

Mateos MV et al. Proc ASH 2013;Abstract 403.

Multiple Myeloma in Session 2015: An Online Journal Club for Hematology/Oncology Fellows This program is supported by educational grants from Celgene Corporation.

KEYNOTE-012: Durable Efficacy With Pembrolizumab in PD-L1–Positive Gastric Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*

Multiple Myeloma in Session 2015: An Online Journal Club for Hematology/Oncology Fellows This program is supported by educational grants from Celgene Corporation.

Elotuzumab, Lenalidomide, and Low-Dose Dexamethasone in Relapsed/Refractory Myeloma Slideset on: Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in combination.

San Miguel JF et al. 1 Proc EHA 2013;Abstract S1151.

Goede V et al. Proc ASH 2014;Abstract 3327.

Dimopoulos MA et al. Proc ASH 2012;Abstract LBA-6.

Attal M et al. Proc ASCO 2010;Abstract 8018.

Fowler NH et al. Proc ASCO 2010;Abstract 8036.

Meletios A. Dimopoulos, MD

Anthracycline Dose Intensification in Acute Myeloid Leukemia

Niesvizky R et al. Proc ASH 2010;Abstract 619.

Palumbo A et al. Proc ASCO 2011;Abstract 8007.

Coiffier B et al. Proc ASH 2010;Abstract 857.

Vitolo U et al. Proc ASH 2011;Abstract 777.

What is the best frontline regimen for CLL patients

Phase III MAIA: Daratumumab + Len/Dex vs Len/Dex in Transplantation-Ineligible Newly Diagnosed Multiple Myeloma Integrating New Malignant Hematology Findings.

Pomalidomide plus Low-Dose Dexamethasone in Myeloma Refractory to Both Bortezomib and Lenalidomide: Comparison of Two Dosing Strategies in Dual-Refractory.

Boccadoro M et al. Proc ASCO 2011;Abstract 8020.

Maintenance therapies in Multiple Myeloma

Presentation transcript:

GEM2005MAS65 Trial: Bortezomib-Based Maintenance Increases CR Rate and PFS in Elderly Patients With Newly Diagnosed Multiple Myeloma Slideset on: Mateos MV, Oriol A, Martínez-López J, et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012;120:2581-2588. This program is supported by educational grants from

Background Maintenance therapy with novel agents an important challenge in elderly patients with MM Thalidomide: in data from MP vs MPT trials, thalidomide maintenance upgraded response and improved PFS but provided only a marginal improvement in OS Lenalidomide: maintenance improved PFS but not OS in the ongoing MM-015 trial[1] Bortezomib: improved 3-yr PFS (but no OS benefit) for VMP plus thalidomide induction followed by VT maintenance vs VMP induction with no maintenance[2] MM, multiple myeloma; MP, melphalan/prednisone; MPT, melphalan/prednisone/thalidomide; OS, overall survival; PFS, progression-free survival; VMP, bortezomib/melphalan/prednisone; VP, bortezomib/prednisone; VT, bortezomib/thalidomide; VTP, bortezomib/thalidomide/prednisone Palumbo A, et al. N Engl J Med. 2012;366:1759-1769. 2. Palumbo A, et al. J Clin Oncol. 2010;28:5101-5109.

Rationale GEM2005MAS65: randomized study VMP or VTP induction followed by VT or VP maintenance in 260 elderly patients with untreated MM Previously reported from this trial: bortezomib-based induction followed by maintenance safe and effective in elderly patients with MM[1] Current analysis: compare efficacy and toxicity of VT maintenance therapy vs VP in elderly patients with newly diagnosed MM enrolled in GEM2005MAS65[2] MM, multiple myeloma; MP, melphalan/prednisone; MPT, melphalan/prednisone/thalidomide; OS, overall survival; PFS, progression-free survival; VMP, bortezomib/melphalan/prednisone; VP, bortezomib/prednisone; VT, bortezomib/thalidomide; VTP, bortezomib/thalidomide/prednisone 1. Mateos MV, et al. Lancet Oncol. 2010;11:934-941. 2. Mateos MV, et al. Blood. 2012;120:2581-2588.

GEM2005MAS65: Study Design Induction: 6 wks Maintenance: up to 3 yrs VP Bortezomib 1.3 mg/m2 twice/wk (Days 1, 4, 8, 11) every 3 mos Prednisone 50 mg every 48 hrs (n = 44) VMP 6 cycles of Bortezomib 1.3 mg/m2 twice/wk* Melphalan 9 mg/m2 on Days 1-4 Prednisone 60 mg/m2 on Days 1-4 (n = 130) VT Bortezomib 1.3 mg/m2 twice/wk (Days 1, 4, 8, 11) every 3 mos Thalidomide 50 mg/day (n = 47) Elderly patients (≥ 65 yrs) with newly diagnosed MM (N = 260) VP Bortezomib 1.3 mg/m2 twice/wk (Days 1, 4, 8, 11) every 3 mos Prednisone 50 mg every 48 hrs (n = 43) MM, multiple myeloma; VMP, bortezomib/melphalan/prednisone; VP, bortezomib/prednisone; VT, bortezomib/thalidomide , VTP, bortezomib/thalidomide/prednisone VTP 6 cycles of Bortezomib 1.3 mg/m2 twice/wk* Thalidomide 100 mg/day Prednisone 60 mg/m2 on Days 1-4 (n = 130) VT Bortezomib 1.3 mg/m2 twice/wk (Days 1, 4, 8, 11) every 3 mos Thalidomide 50 mg/day (n = 44) *Days 1, 4, 8, 11, 22, 25, 29, 32 for one 6-wk course, then on Days 1, 8, 15, 22 for five 5-wk courses Mateos MV, et al. Blood. 2012;120:2581-2588.

Description of Current Analysis Assessment of safety and efficacy in randomized comparison of maintenance therapy with VT or VP FISH studies conducted in CD138-purified plasma cells Response assessment according to EBMT criteria Standard CR; IF-negative CR; IF-positive near CR Assessments performed monthly during maintenance Median follow-up: 38 mos from maintenance therapy initiation (range: 8-58) CR, complete response; FISH, fluorescence in-situ hybridization; IF, immunofixation; nCR, near-complete response; VMP, bortezomib/melphalan/prednisone; VP, bortezomib/prednisone; VT, bortezomib/thalidomide , VTP, bortezomib/thalidomide/prednisone Mateos MV, et al. Blood. 2012;120:2581-2588.

Eligibility Inclusion criteria 65 yrs of age or older Transplantation ineligible Newly diagnosed symptomatic MM Measurable disease No previous treatment MM, multiple myeloma Mateos MV, et al. Blood. 2012;120:2581-2588.

Baseline Characteristics 178 patients randomized for maintenance and evaluable for response Characteristic VT (n = 91) VP (n = 87) Male, % 53 47 Mean age, yrs (range) 71 (66-82) 72 (65-84) ISS stage, % I 30 28 II 41 III 29 IgG/IgA/light chain, % 62/28/9 55/32/12 Mean β2-microglobulin, mg/L 3.7 3.8 Mean creatinine, mg/dL 1.0 Mean plasma cell bone marrow infiltration 38 44 Induction regimen, % VMP 52 51 VTP 48 49 High-risk cytogenetics by FISH,* % 17 15 FISH, fluorescence in-situ hybridization; ISS, international staging system; IgA, immunoglobulin A; IgG, immunoglobulin G; VMP, bortezomib/melphalan/prednisone; VP, bortezomib/prednisone; VT, bortezomib/thalidomide , VTP, bortezomib/thalidomide/prednisone *t(4;14), t(14;16), or del17p. Mateos MV, et al. Blood. 2012;120:2581-2588.

CR Rate After Induction Response, % Premaintenance VT (n = 91) VP (n = 87) P Value IF-negative CR 24 46 39 NS IF-positive CR 10 11 PR 47 MR 8 3 1 SD CR, complete response; IF, immunofixation; MR, minor response; NS, not significant; PR, partial response; SD, stable disease Mateos MV, et al. Blood. 2012;120:2581-2588.

Proportion of Patients Proportion of Patients PFS and OS Median PFS and 5-yr OS superior among patients randomized to VT vs VP maintenance, but the differences did not reach statistical significance PFS OS 1.0 1.0 YT: not reached 5-yr OS: 69% 0.8 0.8 VT: 39 mos 0.6 0.6 VT: 60 mos Proportion of Patients Proportion of Patients OS, overall survival; PFS, progression-free survival; VP, bortezomib/prednisone; VT, bortezomib/thalidomide VT: 39 mos 0.4 0.4 0.2 0.2 P = .1 P = .1 0.0 0.0 10 20 30 40 50 60 10 20 30 40 50 60 Months Months Mateos MV, et al. Blood. 2012;120:2581-2588.

PFS and OS According to Response Achievement of CR significantly associated with longer PFS and 5-yr OS (P < .001) PFS OS 1.0 1.0 CR 0.8 0.8 CR PR 0.6 0.6 Proportion of Patients Near CR Proportion of Patients Near CR CI, confidence interval; CR, complete response; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; VP, bortezomib/prednisone; VT, bortezomib/thalidomide 0.4 PR 0.4 0.2 0.2 P > 0.0001 (HR: 1.73; 95% Cl: 1.4-2.1) P > 0.0001 (HR: 1.5; 95% Cl: 1.2-1.9) 0.0 0.0 10 20 30 40 50 60 70 10 20 30 40 50 60 70 Months Months Mateos MV, et al. Blood. 2012;120:2581-2588.

Depth of Response Patients with improved depth of response during maintenance had better outcomes vs patients who only maintained response Median PFS: 47 vs 32 mos, respectively (HR: 0.56; 95% CI: 0.3-0.9; P = .02) 5-yr OS: 81% vs 54%, respectively (HR: 0.4; 95% CI: 0.10-1.01; P = .02) These outcomes not influenced by the type of maintenance regimen FISH analysis completed for 160 (89%) of patients randomized to receive maintenance Distribution by treatment arms balanced across both risk subgroups CI, confidence interval; CR, complete response; FISH, fluorescence in-situ hybridization; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; Mateos MV, et al. Blood. 2012;120:2581-2588.

Response According to Patient Risk Type of maintenance regimen did not influence response in high-risk or standard-risk patients Response, % Standard Risk (n = 111) High Risk (n = 28) P Value VT VP IF-negative CR 48 41 47 39 NS IF-positive CR 10 11 7 8 PR 37 45 40 54 MR 3 2 CR, complete response; IF, immunofixation; MR, minor response; NS, not significant; PR, partial response Mateos MV, et al. Blood. 2012;120:2581-2588.

PFS and OS According to Patient Risk Differences in PFS and OS by risk minimal and did not reach statistical significance High-risk subgroup for VT vs VP Median PFS: 28 vs 27 mos, respectively (P = .6) 4-yr OS: 55% vs 53%, respectively (P = .2) Standard-risk subgroup Median PFS: slightly higher with VT (47 vs 36 mos; P = .1) 4-yr OS: 79% vs 69% for VT vs VP (P = .1) OS, overall survival; PFS, progression-free survival; VP, bortezomib/prednisone; VT, bortezomib/thalidomide Mateos MV, et al. Blood. 2012;120:2581-2588.

Hematologic Toxicity AEs, % VT (n = 91) VP (n = 87 ) P Value Grade 3/4 AEs All 17 5 .009 Peripheral neuropathy 9 3 Asthenia 2 Gastrointestinal symptoms 4 1* Cardiac events Discontinuations 57 59 Reason for discontinuation Disease progression 35 46 Toxicity 13 Development of SPM Deaths 26 21 30 Development of AEs 6 AEs, adverse events; SPM, second primary malignancies *Gastrointestinal symptomatology and other cardiac events. Mateos MV, et al. Blood. 2012;120:2581-2588.

Hematologic Toxicity Second primary malignancies encountered: AEs: Lung, colorectal, prostate, and lung and liver metastases of unknown origin AEs: Heart attack, stroke, hepatic/lung metastasis, lung cancer, septic shock in VT arm; sepsis, colorectal neoplasm, progressive cognitive impairment, intracerebral hemorrhage in VP arm AE, adverse event; VP, bortezomib/prednisone; VT, bortezomib/thalidomide Mateos MV, et al. Blood. 2012;120:2581-2588.

Summary Bortezomib-based maintenance increases CR rate and PFS in elderly patients with newly diagnosed MM Achievement of CR associated with significantly longer PFS (P < .001) and 5-yr OS (P < .001) Median PFS and OS higher with VT vs VP but differences did not reach statistical significance Overall acceptable toxicity profile with bortezomib-based maintenance More grade 3/4 peripheral neuropathy with VT vs VP Maintenance with VT or VP does not overcome the adverse prognosis associated with high-risk cytogenetic features CR, complete response; OS, overall survival; PFS, progression-free survival; VP, bortezomib/prednisone; VT, bortezomib/thalidomide Mateos MV, et al. Blood. 2012;120:2581-2588.