Reeder CB et al. ASCO 2009; Abstract (Poster)

Slides:

Advertisements

Similar presentations

Moskowitz CH et al. Proc ASH 2014;Abstract 290.

Advertisements

Brown JR et al. Proc ASH 2013;Abstract 523.

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

Novel Agents for Indolent Lymphoma and Mantle Cell Lymphoma Stephen Ansell, MD, PhD Mayo Clinic.

Results of a Phase II Trial of Brentuximab Vedotin as First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT Chen RW et al. Proc ASH 2014;Abstract.

Single-Agent Lenalidomide in Patients with Relapsed/Refractory Mantle Cell Lymphoma Following Bortezomib: Efficacy, Safety and Pharmacokinetics from the.

Rituximab Maintenance: Stage III/IV Follicular Lymphoma (ECOG/CALGB E1496) Subset: 237 FL pts CVP x 6-8 → PR/CR (cyclophosphamide, vincristine, prednisone)

SAR650984, a CD38 Monoclonal Antibody in Patients with Selected CD38+ Hematological Malignancies — Data from a Dose-Escalation Phase I Study Martin TG.

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

Interim Results of an International, Multicenter, Phase 2 Study of Bruton’s Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in Relapsed or Refractory.

A Phase 2 Study of Elotuzumab in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Updated.

Phase III Trial of Pazopanib in Locally Advanced and/or Metastatic Renal Cell Carcinoma Sternberg CN et al. ASCO 2009; Abstract (Oral Presentation)

Ibrutinib in Combination with Bendamustine and Rituximab Is Active and Tolerable in Patients with Relapsed/Refractory CLL/SLL: Final Results of a Phase.

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

Ibrutinib, Single Agent or in Combination with Dexamethasone, in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Preliminary Phase.

Ruan J et al. Proc ASH 2013;Abstract 247.

Lenalidomide Is Safe and Active in Waldenstrom Macroglobulinemia (WM) 1 Updated Results from a Multicenter, Open-Label, Dose-Escalation Phase 1b/2 Study.

The Bruton’s Tyrosine Kinase Inhibitor PCI is Highly Active as Single-Agent Therapy in Previously-Treated Mantle Cell Lymphoma (MCL): Preliminary.

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

Cortés J et al. ASCO 2009; Abstract (Poster Discussion)

A Phase 2 Study of Elotuzumab in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Lonial.

Results of a Randomized Phase 2 Study of PD , a Cyclin ‐ Dependent Kinase (CDK) 4/6 Inhibitor, in Combination with Letrozole vs Letrozole Alone.

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy as Frontline Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell.

ClaPD (Clarithromycin, Pomalidomide, Dexamethasone) Therapy in Relapsed or Refractory Multiple Myeloma Mark TM et al. Proc ASH 2012;Abstract 77.

A Phase 1 Study of the Selective Phosphatidylinositol 3-Kinase-Delta (PI3Kδ) Inhibitor, Idelalisib (GS- 1101) in Combination with Rituximab and/or Bendamustine.

An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab,

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

Responses to Subsequent Anti-HER2 Therapy After Treatment with Trastuzumab-DM1 in Women with HER2- Positive Metastatic Breast Cancer 1 A Phase Ib/II Trial.

Phase II Multicenter Study of Single-Agent Lenalidomide in Subjects with Mantle Cell Lymphoma Who Relapsed or Progressed After or Were Refractory to Bortezomib:

VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination with Bortezomib in Patients with Relapsed or Refractory.

Brentuximab Vedotin in Combination with RCHOP as Front-Line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study Yasenchak CA et al. Proc.

Phase II Study: Pembrolizumab + Pomalidomide/Dexamethasone for Patients With R/R MM New Findings in Hematology: Independent Conference Coverage* of ASH.

New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida ARRAY : Phase II Trial of Carfilzomib.

Preliminary Results of a Multicenter Phase II Trial of 5-Day Decitabine as Front-Line Therapy for Elderly Patients with Acute Myeloid Leukemia (AML) Cashen.

CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 Phase II MONARCH 1: CDK4/6 Inhibitor Abemaciclib in HR+/HER2- MBC.

CCO Independent Conference Coverage

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

Campos M et al. Proc EHA 2013;Abstract B2009.

Campos M et al. Proc EHA 2013;Abstract B2009.

CCO Independent Conference Coverage

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

Phase II PCYC-1121 Trial: Ibrutinib Monotherapy Active in R/R Marginal Zone Lymphoma New Findings in Hematology: Independent Conference Coverage of ASH.

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

Nivolumab in Patients (Pts) with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Clinical Outcomes from Extended Follow-up of a Phase 1 Study.

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.

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

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

Vahdat L et al. Proc SABCS 2012;Abstract P

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

Fujiwara H et al. Proc ASH 2015;Abstract 181.

KEYNOTE-023: Pembrolizumab + Lenalidomide + Dexamethasone Shows Promising Activity and Safety in R/R MM CCO Independent Conference Coverage* of the 2016.

Phase Ib MMY1001: Daratumumab Plus Pom/Dex for Patients With R/R MM

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.

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

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

Jakubowiak AJ et al. Proc ASH 2010;Abstract 862.

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

Badoux X et al. Proc ASCO 2010;Abstract 6508.

Ansell SM et al. Proc ASH 2012;Abstract 798.

Final Results of a Frontline Phase 1/2 Study of Carfilzomib, Lenalidomide, and Low-Dose Dexamethasone (CRd) in Multiple Myeloma (MM)1 Final Results from.

Faderl S et al. Proc ASCO 2011;Abstract 6503.

Forero-Torres A et al. Proc ASH 2011;Abstract 3711.

Zaja F et al. Proc ASH 2010;Abstract 966.

Ahmadi T et al. Proc ASH 2011;Abstract 266.

Advani RH et al. Proc ASH 2011;Abstract 443.

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

Efficacy of BSI-201, a PARP Inhibitor, in Combination with Gemcitabine/Carboplatin (GC) in Triple Negative Metastatic Breast Cancer (mTNBC): Results.

Presentation transcript:

Reeder CB et al. ASCO 2009; Abstract 8569. (Poster) Efficacy and Safety of Lenalidomide (R) Oral Monotherapy in Patients with Relapsed or Refractory Mantle Cell Lymphoma (MCL): Results From an International Study (NHL-003) Reeder CB et al. ASCO 2009; Abstract 8569. (Poster)

Introduction Lenalidomide (R), an immunomodulatory agent, can enhance T-cell and natural-killer-cell activation leading to an improvement in tumor-cell/T-cell synapse formation in B-cell cancers and an enhancement in immune-mediated MCL cell kill R also exerts antiproliferative activity in MCL via enhanced tumor suppressor gene expression (including p21 and SPARC), G1 cell cycle arrest, caspase activation and apoptosis NHL-002: R in relapsed or refractory MCL: ORR = 53%, DoR = 13.7 mos Current study objectives: Interim subset analysis of patients with MCL (n = 54) evaluable for response in NHL-003 (N = 218 patients with aggressive forms of NHL) Evaluate the ORR, DoR, PFS and safety of single-agent R (25 mg/daily d1-21 q28 days) in patients with MCL who had relapsed or were refractory to at least 1 prior treatment regimen Source: Reeder CB et al. ASCO 2009; Abstract 8569.

Mechanism of Action of Lenalidomide in NHL E2F G1 arrest CDK4/6 Rb Cyclin D p21 CDK2 P Cyclin E Rb Cell cycle progression E2F In NHL, R enhances tumor suppressor genes (including p21) leading to reduced cyclin-dependent kinase (CDK) activity and reduced phosphorylation of pRb, which results in cellular growth arrest in the G0/G1 phases of the cell cycle. Source: Reeder CB et al. ASCO 2009; Abstract 8569.

Patient Characteristics and Objective Response Median time from diagnosis (range) 3.2 yrs (0.4-10.4) Presence of > 1 extranodal site 28% International Prognostic Index score 0-2 3-5 53.7% 46.3% Prior therapies Median no. of prior therapies (range) Refractory to last chemotherapy Prior stem cell transplant Prior bortezomib treatment 3 (1-8) 33.3% 25.9% 32.0% N ORR CR/CRu PR MCL, all patients 54 43% 17% 26% MCL-bortezomib treated 17 53% 18% 35% MCL-stem cell treated 14 57% 14% Source: Reeder CB et al. ASCO 2009; Abstract 8569.

Most Common Grade 3 and 4 Adverse Events (N = 54) Hematologic AEs Neutropenia 22.2% 20.4% Febrile neutropenia 1.9% 3.7% Thrombocytopenia 11.1% Anemia 9.3% Leukopenia 5.6% Nonhematologic AEs Fatigue 0% Dyspnea Abdominal pain Asthenia Acute bronchitis Source: Reeder CB et al. ASCO 2009; Abstract 8569.

Summary and Conclusions Overall, patients with relapsed or refractory, heavily pretreated MCL achieved an ORR = 43%, CR = 17% to single-agent R ORR = 57%, CR = 14% in prior stem cell transplant-treated ORR = 53%, CR = 18% in prior bortezomib-treated Median PFS = 6.2 months and DoR has not yet been reached Most common Grade 3/4 AEs: neutropenia (43%), thrombocytopenia (22%) and anemia (11%) 13% of patients discontinued R due to AEs 28% of patients had dose reductions due to AEs R is a promising treatment option for patients with MCL Clinical trials with R alone or combined with chemotherapy are ongoing in MCL Source: Reeder CB et al. ASCO 2009; Abstract 8569.