MANAGING CYTOKINE RELEASE SYNDROME (CRS) AND NEUROTOXICITY WITH STEP-FRACTIONATED DOSING OF MOSUNETUZUMAB IN RELAPSED/REFRACTORY (R/R) B-CELL NON-HODGKIN LYMPHOMA (NHL)
Author(s): ,
Sung-Soo Yoon
Affiliations:
Seoul National University Hospital,Seoul,Korea, Republic Of
,
Matthew Matasar
Affiliations:
Memorial Sloan Kettering Cancer Center,New York, NY,United States
,
Laurie H. Sehn
Affiliations:
BC Cancer Centre for Lymphoid Cancer and University of British Columbia,Vancouver, BC,Canada
,
Sarit Assouline
Affiliations:
Jewish General Hospital,Montreal, QC,Canada
,
Nancy L. Bartlett
Affiliations:
Siteman Cancer Center, Washington University School of Medicine,St. Louis, MO,United States
,
Francesc Bosch
Affiliations:
University Hospital Vall d’Hebron,Barcelona,Spain
,
Catherine M. Diefenbach
Affiliations:
New York University Medical Center,New York, NY,United States
,
Ian Flinn
Affiliations:
Sarah Cannon Research Institute/Tennessee Oncology,Nashville, TN,United States
,
Jung Yong Hong
Affiliations:
ASAN Medical Center,Seoul,Korea, Republic Of
,
Wonseog S. Kim
Affiliations:
Samsung Medical Center,Seoul,Korea, Republic Of
,
Loretta Nastoupil
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Stephen J Schuster
Affiliations:
University of Pennsylvania,Philadelphia, PA,United States
,
Mazyar Shadman
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle, WA,United States
,
Brendan Bender
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Wayne Chu
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Genevive Hernandez
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Antonia Kwan
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Bruce McCall
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Iris Sison
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Cunlin Wang
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Michael C. Wei
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Shen Yin
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Kasra Yousefi
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
Elizabeth L. Budde
Affiliations:
City of Hope Comprehensive Cancer Center,Duarte, CA,United States
EHA Library. Yoon S. 06/15/19; 266711; PS1094
Sung-Soo Yoon
Sung-Soo Yoon
Contributions
Abstract

Abstract: PS1094

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
T-cell directed therapies (e.g. CAR-T, blinatumomab) are associated with significant risk of Grade (Gr) ≥3 neurotoxicity and CRS/infusion-related reaction (IRR). Mosunetuzumab is a CD20/CD3 bispecific antibody that directs T-cells to engage and eliminate malignant B-cells.

Aims
To report safety results from an ongoing Phase 1/1b study (NCT02500407) of mosunetuzumab in patients (pts) with R/R B-cell NHL.

Methods
Pts received ascending doses on Day 1, Day 8, and Day 15 of Cycle 1 (step-fractionation), then a fixed dose on Day 1 of every 21-day cycle thereafter, up to a maximum of 17 cycles. Primary outcome measures included safety and efficacy.

Results
As of October 23, 2018, 114 pts who received step-fractionated dosing of mosunetuzumab were evaluable for safety (Table). The majority of adverse events (AE) occurred during Cycle 1 and 2. Neurologic AEs (NAE), defined from Nervous System or Psychiatric System Organ Classes, were mostly low grade, transient (median duration 4 days) and reversible; most common were headache (14%) and dizziness (8%). Gr ≥3 NAEs occurred in 4 pts (4%), with only 1 treatment-related event (hepatic encephalopathy). CRS/IRR was reported in 25% of pts, with only 1 Gr 3 event. Most common CRS symptoms were pyrexia (86%), chills (38%), tachycardia and headache (14% each). There were no Gr 5 events related to CRS or NAEs. No apparent dose toxicity relationship was observed with step-fractionation in these pts, despite escalation of the Cycle 1 Day 15 dose to 20 mg, consistent with observed peak IL-6 levels after a low Cycle 1 Day 1 dose. In these pts, objective responses were observed in 24/73 (33%; complete response [CR], 13 [18%]) aggressive NHL and 17/32 (53%; CR, 10 [31%]) indolent NHL pts.

Conclusion
Step-fractionation has enabled continued dose escalation of mosunetuzumab with no apparent increases in toxicity, exhibiting a promising risk-benefit profile.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): CD20, Immunotherapy, Non-Hodgkin's lymphoma, Safety

Abstract: PS1094

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
T-cell directed therapies (e.g. CAR-T, blinatumomab) are associated with significant risk of Grade (Gr) ≥3 neurotoxicity and CRS/infusion-related reaction (IRR). Mosunetuzumab is a CD20/CD3 bispecific antibody that directs T-cells to engage and eliminate malignant B-cells.

Aims
To report safety results from an ongoing Phase 1/1b study (NCT02500407) of mosunetuzumab in patients (pts) with R/R B-cell NHL.

Methods
Pts received ascending doses on Day 1, Day 8, and Day 15 of Cycle 1 (step-fractionation), then a fixed dose on Day 1 of every 21-day cycle thereafter, up to a maximum of 17 cycles. Primary outcome measures included safety and efficacy.

Results
As of October 23, 2018, 114 pts who received step-fractionated dosing of mosunetuzumab were evaluable for safety (Table). The majority of adverse events (AE) occurred during Cycle 1 and 2. Neurologic AEs (NAE), defined from Nervous System or Psychiatric System Organ Classes, were mostly low grade, transient (median duration 4 days) and reversible; most common were headache (14%) and dizziness (8%). Gr ≥3 NAEs occurred in 4 pts (4%), with only 1 treatment-related event (hepatic encephalopathy). CRS/IRR was reported in 25% of pts, with only 1 Gr 3 event. Most common CRS symptoms were pyrexia (86%), chills (38%), tachycardia and headache (14% each). There were no Gr 5 events related to CRS or NAEs. No apparent dose toxicity relationship was observed with step-fractionation in these pts, despite escalation of the Cycle 1 Day 15 dose to 20 mg, consistent with observed peak IL-6 levels after a low Cycle 1 Day 1 dose. In these pts, objective responses were observed in 24/73 (33%; complete response [CR], 13 [18%]) aggressive NHL and 17/32 (53%; CR, 10 [31%]) indolent NHL pts.

Conclusion
Step-fractionation has enabled continued dose escalation of mosunetuzumab with no apparent increases in toxicity, exhibiting a promising risk-benefit profile.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): CD20, Immunotherapy, Non-Hodgkin's lymphoma, Safety

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