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.

Slides:

Advertisements

Similar presentations

Allogeneic Transplant Following Brentuximab Vedotin Treatment in Patients with Relapsed or Refractory CD30+ Lymphomas Illidge T et al. Proc ASH 2011;Abstract.

Advertisements

Gopal AK et al. Proc ASH 2013;Abstract 4382.

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

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

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

1Coiffier B et al. Proc ASH 2010;Abstract 114.

Belinostat, a Novel Pan-Histone Deactylase Inhibitor (HDACi), in Relapsed or Refractory Peripheral T-Cell Lymphoma: Results from the BELIEF Trial1 Belinostat.

Richardson PG et al. Proc ASH 2013;Abstract 535.

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

LaCasce A et al. Proc ASH 2014;Abstract 293.

Roberts AW et al. Proc ASH 2014;Abstract 325.

Lesokhin AM et al. Proc ASH 2014;Abstract 291.

Efficacy of Denileukin Diftitox Retreatment in Patients with Cutaneous T-Cell Lymphoma Who Relapsed After Initial Response 1 Identification of an Active,

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

ECHELON-2: Phase 3 Trial of Brentuximab Vedotin and CHP versus CHOP in the Frontline Treatment of Patients (Pts) with CD30+ Mature T-Cell Lymphomas (MTCL)1.

A Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results in Patients with DLBCL.

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.

FDG-PET Adapted Sequential Therapy with Brentuximab Vedotin and Augmented ICE Followed by Autologous Stem Cell Transplant for Relapsed and Refractory Hodgkin.

Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma Younes A et al. Proc.

Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone Followed by Lenalidomide Extended Dosing (CRD-R) Induces High Rates.

Weekly MLN9708, an Investigational Oral Proteasome Inhibitor, in Relapsed/Refractory Multiple Myeloma: Results from a Phase I Study After Full Enrollment.

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

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

Reduced-Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (allo-SCT) for Relapsed/Refractory Hodgkin Lymphoma (HL) in the Brentuximab.

Viardot A et al. Proc ASH 2014;Abstract 4460.

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.

Brentuximab Vedotin (SGN-35) Enables Successful Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Relapsed/Refractory Hodgkin Lymphoma.

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

Locatelli F et al. Proc ASH 2013;Abstract 4378.

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

A Phase 3 Prospective, Randomized, International Study (MMY-3021) Comparing Subcutaneous and Intravenous Administration of Bortezomib in Patients with.

A Phase 2 Study of Single-Agent Brentuximab Vedotin for Front- Line Therapy of Hodgkin Lymphoma in Patients Age 60 Years and Above: Interim Results Yasenchak.

Bortezomib (BTZ) and Panobinostat (PAN) Combination Is Effective in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) or NK/T-Cell Lymphoma.

A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma Shah.

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

Moskowitz CH et al. Proc ASH 2014;Abstract 673.

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

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

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.

Results of a Phase 2, Multicenter, Single-Arm Study of Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic HER2-Negative Breast.

MM-005: A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib,

Romidepsin in Association with CHOP in Patients with Peripheral T-Cell Lymphoma: Final Results of the Phase Ib/II Ro-CHOP Study Dupuis J et al. Proc ASH.

Final Results for the 1703 Phase 1b/2 Study of Elotuzumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple.

Vose JM et al. Proc ASH 2011;Abstract 661.

Moskowitz CH et al. Proc ASH 2015;Abstract 182.

Chen R et al. Proc ASH 2015;Abstract 518.

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

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

Shustov AR et al. Proc ASH 2010;Abstract 961.

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.

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

Oki Y et al. Proc ASH 2013;Abstract 252.

Vahdat L et al. Proc SABCS 2012;Abstract P

KEYNOTE-087: Pembrolizumab in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma New Findings in Hematology: Independent Conference Coverage.

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

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

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.

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

Ferrajoli A et al. Proc ASH 2010;Abstract 1395.

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

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

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.

Presentation transcript:

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 501.

Background Brentuximab vedotin (BV) is an antibody-drug conjugate that selectively induces the apoptosis of CD30-positive cells. A Phase II trial demonstrated an overall response rate (ORR) of 75%, with a complete response (CR) rate of 34% and a favorable toxicity profile in Hodgkin Lymphoma (HL) after autologous hematopoietic cell transplant (AHCT) (JCO 2012;30(18):2183). Standard first-line salvage regimens such as ICE have similar response rates but have more serious toxicities. Study objective: To determine the efficacy and safety of BV as first-line salvage therapy for patients with relapsed/refractory HL prior to AHCT. Chen RW et al. Proc ASH 2014;Abstract 501.

Phase II Trial Design Eligibility (n = 37) Confirmed CD30+ HL at relapse Prior failure of induction treatment with ABVD or BEACOPP or ABVE-PC Radiographic assessments with CT or PET scans were done after 2 cycles. Patients who achieved CR, partial response (PR) or stable disease (SD) were allowed to receive 2 more cycles -Achievement of CR = stem cell mobilization  transplantation -Achievement of PR, depending on the amount of resistant disease = transplantation or salvage therapy Primary endpoint: ORR Secondary endpoints included: Toxicity, stem cell mobilization rate, engraftment analysis and biomarker assessment Dose amended to 2.4 mg/kg after cycle 2 for patients not achieving CR because of risk of progression 1.8 mg/kg of BV (IV) Every 3 weeks Up to 4 cycles Chen RW et al. Proc ASH 2014;Abstract 501.

Response Best response n = 36* ORR69% CR13 (36%) PR12 (33%) SD10 (28%) Progressive disease (PD)1 (3%) * Evaluable patients No correlation between CD68 expression levels and response rates Chen RW et al. Proc ASH 2014;Abstract 501.

Treatment Outcomes 33/37 (89%) patients successfully proceeded to AHCT: –Patients who received additional chemotherapy: 16 (48%) –Patients who received BV only: 17 (52%) 13 patients with CR and 4/12 with PR went directly to AHCT. 73% were in CR at time of AHCT. 26% were in PR and 3% in SD at time of AHCT. Chen RW et al. Proc ASH 2014;Abstract 501 (Abstract only).

Stem Cell Mobilization Patients were primed with cyclophosphamide/G- CSF/plerixafor Median CD34 cells collected: 5.97 x 10 6 (range x 10 6 ) Median number of days for collection: 2 (range 1-6) Median time to neutrophil engraftment: 11 days (range 10-12) Median time to platelet engraftment: 13 days (range 9-23) Chen RW et al. Proc ASH 2014;Abstract 501 (Abstract only).

Select Adverse Events N = 37 Grade 1/2Grade 3Grade 4 Peripheral neuropathy52%00 Elevated AST37%3%0 Elevated ALT38%00 Rash35%5%0 Fatigue30%00 Anemia19%00 Neutropenia11%5%0 Lymphopenia3% Thrombocytopenia8%00 No patient required growth factor, PRBC or platelet transfusions as a result of BV Chen RW et al. Proc ASH 2014;Abstract 501.

Author Conclusions As first-line salvage therapy, BV is efficacious, well tolerated and does not hinder stem cell mobilization or engraftment. Eighty-nine (89%) of patients experienced an effective bridge to AHCT, and 52% went to AHCT without additional salvage chemotherapy. BV can be considered as first-line salvage for patients with R/R HL after induction therapy. –ORR = 69% –CR rate = 36% Patients not achieving a CR after 2 cycles are at risk for disease progression. Chen RW et al. Proc ASH 2014;Abstract 501.

Investigator Commentary: Results from a Phase II Study of BV as First-Line Salvage Therapy in R/R HL before AHCT This study used standard BV administered for up to 4 cycles in patients before transplant. All patients who achieved a CR underwent AHCT. Patients who did not achieve a CR but were still PET-avid received nonuniform therapy. I believe it will be difficult to evaluate these patients. The results are consistent with all the other studies of BV. Patients who achieved a PR after the first 2 cycles then went on to receive 2 more doses of BV. However, none of these patients' PRs were converted to a CR. If the patient does not achieve a CR early during the course of treatment with BV, perhaps the treating physician should apply a different treatment approach. In this study the choice was to escalate the dose of BV to 2.4 mg/kg for those not achieving a CR by cycle 2. In summary, the overall response rate was high and the CR rate was pretty good. However, the absence of any conversion from PR to CR was disappointing. Interview with Craig Moskowitz, MD, January 6, 2015