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NIVOLUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY LYMPHOID MALIGNANCIES AND CLASSICAL HODGKIN LYMPHOMA: UPDATED SAFETY AND EFFICACY RESULTS OF A PHASE 1 STUDY (CA209-039)
Author(s): ,
Philippe Armand
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
John Timmerman
Affiliations:
Jonsson Comprehensive Cancer Center, University of California,Los Angeles,United States
,
Alexander Lesokhin
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,United States
,
Ahmad Halwani
Affiliations:
University of Utah Huntsman Cancer Institute,Salt Lake City,United States
,
Michael Millenson
Affiliations:
Fox Chase Cancer Center,Philadelphia,United States
,
Stephen Schuster
Affiliations:
Abramson Cancer Center, University of Pennsylvania,Philadelphia,United States
,
Martin Gutierrez
Affiliations:
John Theurer Cancer Center, Hackensack University Medical Center,Hackensack,United States
,
Emma Scott
Affiliations:
Oregon Health and Science University,Portland,United States
,
Deepika Cattry
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,United States
,
Gordon Freeman
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Bjoern Chapuy
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Azra Ligon
Affiliations:
Brigham and Women’s Hospital,Boston,United States
,
Scott Rodig
Affiliations:
Brigham and Women’s Hospital,Boston,United States
,
Lili Zhu
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Joseph Grosso
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Jason Simon
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Margaret Shipp
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Adam Cohen
Affiliations:
Abramson Cancer Center, University of Pennsylvania,Philadelphia,United States
,
Daniel Lebovic
Affiliations:
University of Michigan Hematology,Ann Arbor,United States
,
Madhav Dhodapkar
Affiliations:
Yale Cancer Center,New Haven,United States
,
David Avigan
Affiliations:
Beth Israel Deaconess Medical Center,Boston,United States
,
Stephen Ansell
Affiliations:
Mayo Clinic,Rochester,United States
Ivan Borrello
Affiliations:
Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center,Baltimore,United States
(Abstract release date: 05/21/15) EHA Library. Armand P. 06/14/15; 103093; S808 Disclosure(s): Dana-Farber Cancer Institute
Dr. Philippe Armand
Dr. Philippe Armand
Contributions
Abstract
Abstract: S808

Type: Oral Presentation

Presentation during EHA20: From 14.06.2015 08:45 to 14.06.2015 09:00

Location: Room Lehar 3 + 4

Background
The PD-1 pathway functions as a checkpoint which limits T-cell mediated tumor immune responses. Nivolumab (NIVO), a fully human IgG4 monoclonal PD-1 blocking antibody, potentiates T-cell activity. Prior results from this study (median follow-up 40 weeks) showed that NIVO was tolerated and achieved an overall response rate of 87% in classical Hodgkin lymphoma (cHL), 40% in follicular B-cell lymphoma (FBL), 36% in diffuse large B-cell lymphoma (DLBCL) and 17% in T-cell non-Hodgkin lymphoma (T-NHL). The stable disease rate in multiple myeloma (MM) was 67%. 

Aims
Herein, we report the updated follow-up and safety profile of this study.

Methods
Patients (Pts) were treated using a dose-escalation design (1 and 3 mg/kg) of NIVO administered every 2 weeks (wks) for 2 years. Responses were assessed using standard criteria. Primary endpoint was safety. The secondary endpoint was efficacy. 

Results
105 pts were enrolled (23 cHL, 31 B-NHL, 23 T-NHL, 27 MM and 1 chronic myelogenous leukemia). Pts were heavily pretreated with 88%, 78%, 68% and 66% of pts with cHL, T-NHL, B-NHL and MM, respectively, having received ≥3 prior regimens. Previous ASCT was reported for 75% of pts with cHL, 56% of MM, 13% of B-NHL and 9% of T-NHL. As of 1/8/2015, median duration of follow-up was 62 wks (range: 2 to 106+ wks).

Drug-related adverse events (DrAEs) occurred in 71 (67%) pts. The most common DrAEs occurring in >5% were fatigue (15%), rash (11%), diarrhea, pneumonitis, pruritus (each 9%), pyrexia (8%), thrombocytopenia, decreased appetite (each 7%), hypocalcemia, lipase increased, leukopenia, lymphopenia (each 6%) and nausea (5%). Serious DrAE in ≥5% of pts included pneumonitis (5%).

Efficacy results shown below. The rate of stable disease in MM (n=27) was 63%. Among the 20 responding cHL pts, 10 discontinued NIVO; 6 (1CR and 5 PR) to undergo SCT, 3 for disease progression and 1 for toxicity (MDS, thrombocytopenia) and 10 (7 PR and 3 CR) continue to respond. Among responding B- and T-NHL pts, 1/4 DLBCL, 3/4 FL and 3/4 T-NHL pts remain in response. In this updated analysis, median duration of response has not been reached in cHL, B-NHL and T-NHL.



Summary
Encouraging, durable objective responses were observed in cHL, DLBCL and FL, including CR and PR. NIVO treatment remains safe and tolerable with a safety profile similar to that in solid tumors, and further analysis is warranted in cHL and selected B-NHLs and T-NHLs.

Keyword(s): Hodgkin's lymphoma, Immunotherapy, Multiple myeloma, Non-Hodgkin's lymphoma



Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects
Abstract: S808

Type: Oral Presentation

Presentation during EHA20: From 14.06.2015 08:45 to 14.06.2015 09:00

Location: Room Lehar 3 + 4

Background
The PD-1 pathway functions as a checkpoint which limits T-cell mediated tumor immune responses. Nivolumab (NIVO), a fully human IgG4 monoclonal PD-1 blocking antibody, potentiates T-cell activity. Prior results from this study (median follow-up 40 weeks) showed that NIVO was tolerated and achieved an overall response rate of 87% in classical Hodgkin lymphoma (cHL), 40% in follicular B-cell lymphoma (FBL), 36% in diffuse large B-cell lymphoma (DLBCL) and 17% in T-cell non-Hodgkin lymphoma (T-NHL). The stable disease rate in multiple myeloma (MM) was 67%. 

Aims
Herein, we report the updated follow-up and safety profile of this study.

Methods
Patients (Pts) were treated using a dose-escalation design (1 and 3 mg/kg) of NIVO administered every 2 weeks (wks) for 2 years. Responses were assessed using standard criteria. Primary endpoint was safety. The secondary endpoint was efficacy. 

Results
105 pts were enrolled (23 cHL, 31 B-NHL, 23 T-NHL, 27 MM and 1 chronic myelogenous leukemia). Pts were heavily pretreated with 88%, 78%, 68% and 66% of pts with cHL, T-NHL, B-NHL and MM, respectively, having received ≥3 prior regimens. Previous ASCT was reported for 75% of pts with cHL, 56% of MM, 13% of B-NHL and 9% of T-NHL. As of 1/8/2015, median duration of follow-up was 62 wks (range: 2 to 106+ wks).

Drug-related adverse events (DrAEs) occurred in 71 (67%) pts. The most common DrAEs occurring in >5% were fatigue (15%), rash (11%), diarrhea, pneumonitis, pruritus (each 9%), pyrexia (8%), thrombocytopenia, decreased appetite (each 7%), hypocalcemia, lipase increased, leukopenia, lymphopenia (each 6%) and nausea (5%). Serious DrAE in ≥5% of pts included pneumonitis (5%).

Efficacy results shown below. The rate of stable disease in MM (n=27) was 63%. Among the 20 responding cHL pts, 10 discontinued NIVO; 6 (1CR and 5 PR) to undergo SCT, 3 for disease progression and 1 for toxicity (MDS, thrombocytopenia) and 10 (7 PR and 3 CR) continue to respond. Among responding B- and T-NHL pts, 1/4 DLBCL, 3/4 FL and 3/4 T-NHL pts remain in response. In this updated analysis, median duration of response has not been reached in cHL, B-NHL and T-NHL.



Summary
Encouraging, durable objective responses were observed in cHL, DLBCL and FL, including CR and PR. NIVO treatment remains safe and tolerable with a safety profile similar to that in solid tumors, and further analysis is warranted in cHL and selected B-NHLs and T-NHLs.

Keyword(s): Hodgkin's lymphoma, Immunotherapy, Multiple myeloma, Non-Hodgkin's lymphoma



Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects

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