TWO DOSES OF POLATUZUMAB VEDOTIN (POV, ANTI-CD79B ANTIBODY-DRUG CONJUGATE) PLUS RITUXIMAB (R) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL): DURABLE RESPONSES AT LOWER DOSE LEVEL
Author(s): ,
Jeff Sharman
Affiliations:
US Oncology and Willamette Valley Cancer Institute,Springfield,United States
,
Ian Flinn
Affiliations:
Sarah Cannon Research Institute and Tennessee Oncology,Nashville,United States
,
Ranjana Advani
Affiliations:
Stanford Cancer Center,Stanford,United States
,
Catherine Diefenbach
Affiliations:
New York University Medical Center,New York,United States
,
Kathryn Kolibaba
Affiliations:
US Oncology and Compass Oncology,Vancouver,Canada
,
Oliver Press
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States
,
Laurie Sehn
Affiliations:
BC Cancer Agency,Vancouver,Canada
,
Andy Chen
Affiliations:
Oregon Health & Science University,Portland,United States
,
Gilles Salles
Affiliations:
Hospices Civils de Lyon,Pierre-Benite,France
,
Herve Tilly
Affiliations:
Centre Henri Becquerel,Rouen,France
,
Bruce Cheson
Affiliations:
Georgetown University Hospital,Washington DC,United States
,
Sarit Assouline
Affiliations:
Jewish General Hospital,Montreal,Canada
,
Martin Dreyling
Affiliations:
Klinikum der Universität München,München,Germany
,
Anton Hagenbeek
Affiliations:
Academic Medical Center,Amsterdam,Netherlands
,
Pier Luigi Zinzani
Affiliations:
University of Bologna,Bologna,Italy
,
Cheryl Jones
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Surai Jones
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Wayne Chu
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Jamie Hirata
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Michael Wenger
Affiliations:
Genentech, Inc.,South San Francisco,United States
Franck Morschhauser
Affiliations:
Hopital Claude Huriez,Lille Cedex,France
EHA Library. Sharman J. 06/13/15; 100829; P688
Jeff Sharman
Jeff Sharman
Contributions
Abstract
Abstract: P688

Type: Poster Presentation

Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

Location: Poster area (Hall C)

Background
Based on early evidence of cumulative toxicity of PoV at a dose of 2.4 mg/kg (Morschhauser ASH 2014; NCT01691898), a dose of 1.8 mg/kg dose was explored. 

Aims
To report updated results of the dose comparison. Safety and efficacy of PoV after 8 treatment cycles were also analyzed.

Methods
Patients (pts) with R/R FL received PoV at 2.4 mg/kg or 1.8 mg/kg with R 375mg/m2, q21d until progression or unacceptable toxicity. Five pts with R/R FL from the Phase 1 study (Palanca-Wessels ASH 2013) treated with PoV 2.4 mg/kg were included in the analysis. Data at completion of PoV treatment were compared with data after 8 cycles.

Results
Forty-five pts received PoV + R (25, 2.4 mg/kg; 20, 1.8 mg/kg). Median follow-up was 14 mo. for 2.4 mg/kg vs. 8 mo. for 1.8 mg/kg. When limited to the first 8 treatment cycles, median follow-up was similar at 6 mo. for both groups. Baseline characteristics were balanced between the two cohorts, except for age (median 68 yrs 2.4 mg/kg, 62 yrs 1.8 mg/kg) and tumor volume (SPD 1824 mm2 at 2.4 mg/kg, 2655mm2 at 1.8 mg/kg). Overall, 40% (10/25, 2.4 mg/kg) and 50% (10/20, 1.8 mg/kg) of pts were refractory to their last treatment. At data cut-off for this analysis, pts received a median of 10 and 9.5 treatment cycles in the 2.4 mg/kg and 1.8 mg/kg groups, respectively, with median dose intensities after cycle 8 of 88% and 99%, respectively. Safety is shown in the Table.  Peripheral neuropathy (PN) was more frequent with PoV 2.4 mg/kg, and discontinuation (d/c) rates due to all causes were 56% vs. 30% with the 1.8 mg/kg dose. After 8 treatment cycles, d/c rates were similar for both doses (28% vs. 25%). An 84-year old pt in the 2.4 mg/kg cohort died 2 mo. after cycle 12 due to pulmonary congestion.

Safety profiles of PoV+R for all treatment cycles and truncated after cycle 8

 Adverse events, n (%)

(MeDRA SOC)

PoV

1.8 mg/kg

all cycles (N=20)

PoV

2.4 mg/kg

all cycles (N=25)

PoV

1.8 mg/kg

8 cycles (N=20)

PoV

2.4 mg/kg

8 cycles (N=25)

Any AE Grade 3-4

10 (50)

13 (52)

10 (50)

13 (52)

Neutropenia

7 (35)

4 (16)

7 (35)

4 (16)

Febrile neutropenia

2 (10)

1 (4)

2 (10)

1 (4)

Serious AE

6 (30)

8 (32)

6 (30)

6 (24)

Deaths

1 (4)

AE leading to study discontinuation

6 (30)

14 (56)

5 (25)

7 (28)

Grade 2-4 periph. neuropathy1

8 (40)

18 (72)

5 (25)

10 (40)

Grade 3+ infection

1 (5)

3 (12)

1 (5)

2 (8)

AE per CTCAE V4.03. AEs G3/4 ≥10% reported; 1 MedDRA SMQ peripheral neuropathy (wide)

ORR was similar in for both levels: 19/25 (76%) at 2.4 mg/kg, 15/20 (75%) at 1.8 mg/kg. CRs were achieved in 11/25 (44%) patients at 2.4 mg/kg and 2/20 (10%) patients at 1.8 mg/kg. Duration of response was 12 mo. for 2.4 mg/kg and not estimable for 1.8 mg/kg group. After 8 cycles, ORR remained similar; 64% for 2.4 mg/kg and 60% for 1.8 mg/kg. Median PFS was 15 mo. at 2.4 mg/kg and not reached in the 1.8 mg/kg group (Figure). 



Summary
PoV+R in R/R FL showed high ORR at both doses, with higher CR at 2.4 mg/kg. D/c rates, mostly due to cumulative PN, were high. AEs and d/c rates were reduced at both doses if only the first 8 cycles are considered vs. those reported through study completion. The safety of PoV can be improved by shorter treatment and/or lower dose. Updated PFS will be presented. 

Keyword(s): B cell lymphoma, Follicular lymphoma, Indolent non-Hodgkin's lymphoma



Session topic: Indolent Non-Hodgkin lymphoma - Clinical
Abstract: P688

Type: Poster Presentation

Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

Location: Poster area (Hall C)

Background
Based on early evidence of cumulative toxicity of PoV at a dose of 2.4 mg/kg (Morschhauser ASH 2014; NCT01691898), a dose of 1.8 mg/kg dose was explored. 

Aims
To report updated results of the dose comparison. Safety and efficacy of PoV after 8 treatment cycles were also analyzed.

Methods
Patients (pts) with R/R FL received PoV at 2.4 mg/kg or 1.8 mg/kg with R 375mg/m2, q21d until progression or unacceptable toxicity. Five pts with R/R FL from the Phase 1 study (Palanca-Wessels ASH 2013) treated with PoV 2.4 mg/kg were included in the analysis. Data at completion of PoV treatment were compared with data after 8 cycles.

Results
Forty-five pts received PoV + R (25, 2.4 mg/kg; 20, 1.8 mg/kg). Median follow-up was 14 mo. for 2.4 mg/kg vs. 8 mo. for 1.8 mg/kg. When limited to the first 8 treatment cycles, median follow-up was similar at 6 mo. for both groups. Baseline characteristics were balanced between the two cohorts, except for age (median 68 yrs 2.4 mg/kg, 62 yrs 1.8 mg/kg) and tumor volume (SPD 1824 mm2 at 2.4 mg/kg, 2655mm2 at 1.8 mg/kg). Overall, 40% (10/25, 2.4 mg/kg) and 50% (10/20, 1.8 mg/kg) of pts were refractory to their last treatment. At data cut-off for this analysis, pts received a median of 10 and 9.5 treatment cycles in the 2.4 mg/kg and 1.8 mg/kg groups, respectively, with median dose intensities after cycle 8 of 88% and 99%, respectively. Safety is shown in the Table.  Peripheral neuropathy (PN) was more frequent with PoV 2.4 mg/kg, and discontinuation (d/c) rates due to all causes were 56% vs. 30% with the 1.8 mg/kg dose. After 8 treatment cycles, d/c rates were similar for both doses (28% vs. 25%). An 84-year old pt in the 2.4 mg/kg cohort died 2 mo. after cycle 12 due to pulmonary congestion.

Safety profiles of PoV+R for all treatment cycles and truncated after cycle 8

 Adverse events, n (%)

(MeDRA SOC)

PoV

1.8 mg/kg

all cycles (N=20)

PoV

2.4 mg/kg

all cycles (N=25)

PoV

1.8 mg/kg

8 cycles (N=20)

PoV

2.4 mg/kg

8 cycles (N=25)

Any AE Grade 3-4

10 (50)

13 (52)

10 (50)

13 (52)

Neutropenia

7 (35)

4 (16)

7 (35)

4 (16)

Febrile neutropenia

2 (10)

1 (4)

2 (10)

1 (4)

Serious AE

6 (30)

8 (32)

6 (30)

6 (24)

Deaths

1 (4)

AE leading to study discontinuation

6 (30)

14 (56)

5 (25)

7 (28)

Grade 2-4 periph. neuropathy1

8 (40)

18 (72)

5 (25)

10 (40)

Grade 3+ infection

1 (5)

3 (12)

1 (5)

2 (8)

AE per CTCAE V4.03. AEs G3/4 ≥10% reported; 1 MedDRA SMQ peripheral neuropathy (wide)

ORR was similar in for both levels: 19/25 (76%) at 2.4 mg/kg, 15/20 (75%) at 1.8 mg/kg. CRs were achieved in 11/25 (44%) patients at 2.4 mg/kg and 2/20 (10%) patients at 1.8 mg/kg. Duration of response was 12 mo. for 2.4 mg/kg and not estimable for 1.8 mg/kg group. After 8 cycles, ORR remained similar; 64% for 2.4 mg/kg and 60% for 1.8 mg/kg. Median PFS was 15 mo. at 2.4 mg/kg and not reached in the 1.8 mg/kg group (Figure). 



Summary
PoV+R in R/R FL showed high ORR at both doses, with higher CR at 2.4 mg/kg. D/c rates, mostly due to cumulative PN, were high. AEs and d/c rates were reduced at both doses if only the first 8 cycles are considered vs. those reported through study completion. The safety of PoV can be improved by shorter treatment and/or lower dose. Updated PFS will be presented. 

Keyword(s): B cell lymphoma, Follicular lymphoma, Indolent non-Hodgkin's lymphoma



Session topic: Indolent Non-Hodgkin lymphoma - Clinical

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