Brentuximab Vedotin Should be the Second Line Regimen of Choice for Recurrent Hodgkin Lymphoma Prior to Stem Cell Transplant Catherine Diefenbach, MD Assistant Professor of Medicine NYU Perlmutter Cancer Center, NYU Langone Medical Center

ESTABLISHED IS NOT ALWAYS BETTER

Hodgkin Lymphoma Most common lymphoma in the young. Median age at dx: 39yrs 40 % of patients younger than % cured with frontline chemotherapy or chemo-radiotherapy. From Dorothy Reed, 1902

Why Does Relapsed Hodgkin Lymphoma Matter? 25% of patients relapse or have primary refractory dz. These are young patients. ASCT curable in only 50% of patients. No other established curative salvage therapy. Median TTP with relapse after SCT treated with subsequent therapy is 3.8 months Median survival is 26 months.

3 Key Questions in Relapsed HL How do we maximize cure? How do we minimize toxicity? How do we maximize quality of life during therapy?

Conventional Chemotherapy: The Existing Paradigm Do existing regimens for first salvage Rx – Maximize cure - – Minimize toxicity - – Are they convenient? - – Are they cost-effective? - – Can we do better? - NO YES

Survival for Patients Relapsed After Transplant Median PFS 1.3 years. 71% of relapses occurred within 1 year after ASCT. Equally distributed in the following periods: – < 3 months (22%) – > 3 months and < 6 months (22%) – > 6 and < 12 months (27%)

Maximizing Transplant Related Benefit Achieving a before ASCT most important factor in determining long-term DFS. Other post transplant prognostic factors. – Duration of initial remission – Extent of disease at relapse – Constitutional symptoms CR

MAXIMIZING DISEASE CONTROL PRIOR TO TRANSPLANT WILL MAXIMIZE BENEFIT (CURE) FROM TRANSPLANT.

Salvage Chemotherapy is Toxic RegimenReferenceNORR (%)CR (%)Toxicity Dexa-BEAMSchmitz, % toxic deaths Mini-BEAMMartin, % deaths, cytopenias MINEFerme, NA5% toxic deaths ICEMoskowitz, neutropenia ESHAPAparicio, % deaths, cytopenias (59%) MINE-ESHAPFernandez de Larrea, % gr III/IV cytopenias DHAPJosting % gr III/IV cytopenias GDPBaetz, % gr III/IV cytopenias GVDBartlett, % cytopenias DICEPShafrey, % deaths, cytopenias IVOxSibon, % cytopenias O-ESHAPMartinez, % cytopenias

Survival After ICE Chemotherapy Suboptimal 3 Year EFS: 22% Intention to treat (all) EFS post ASCT 52.5% OS post ASCT 44.2% Median survival of patients who did not get Txp 3.7 months

Conclusions All salvage trials small, single arm studies (median N = 61) Myelosuppression common Deaths seen High ORR rates do not equal high CR Median CRR = 33% Most administered in the hospital

Conventional Chemotherapy Fails INADEQUATE DISEASE CONTROL UNACCEPTABLE TOXICITY NOT COST EFFECTIVE NOT CONVENIENT: REQUIRES PATIENTS TO BE HOSPITALIZED

The Alternative: Brentuximab Vedotin Courtesy of Seattle Genetics

Brentuximab Vedotin Highly Active in Relapsed HL Younes et al, NEJM %, ORR 75% CR 34%

Brentuximab as First Salvage Chen et al.

Response Data Brentuximab Second Line ORR 85.7% CR = 50% PR = 35.7% SD = 7.1% POD 7.1% ICE CR = 26% DHAP CR = 21% GVD CR = 19% Compared to 

BRENTUXIMAB IS SIGNIFICANTLY LESS TOXIC THEN CONVENTIONAL SALVAGE Rash is ONLY Grade 3-4 toxicity No Gr3 cytopenias No febrile neutropenia Growth factors support not required Administered outpatient

Successful ASCT after Brentuximab Median cell dose collected 5.87 x 10 6 CD34+ cells. Median time to reach collection = 1 day Median time to neutrophil engraftment 10 days (10- 11) Median time to platelet engraftment 11 days (10-13)

Brentuximab Second Line Moskowitz et al.

Brentuximab Related Toxicities Only 1 Gr 3 toxicity for Brentuximab No neutropenia No fevers No thrombocytopenia Administered outpatient

ICE vs. Brentuximab  ICE 3 year EFS 22% 10 month DFS 92% ICE Brentuximab

Conclusions Maximizing disease control prior to ASCT will maximize cure from ASCT Brentuximab Vedotin –N–Novel Agent –H–High ORR and High CR rate –L–Low toxicity –O–Outpatient administration Conventional chemotherapy: –F–Fails to provide a high CR rate –F–Fails to provide long term disease control –H–Has unacceptable toxicity –R–Requires hospitalization