PHASE 3B STUDY TO EVALUATE DEBULKING REGIMENS PRIOR TO INITIATING VENETOCLAX THERAPY IN UNTREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Author(s): ,
Jeff Sharman
Affiliations:
Willamette Valley Cancer Institute and US Oncology Research,Eugene,United States
,
David Andorsky
Affiliations:
Rocky Mountain Cancer Centers,Boulder,United States
,
Jason Melear
Affiliations:
Texas Oncology-Austin Midtown,Austin,United States
,
Sudhir Manda
Affiliations:
Arizona Oncology Associates, PC-HOPE,Tucson,United States
,
Bertrand Anz III
Affiliations:
Tennessee Oncology Chattanooga,Chattanooga,United States
,
Kathryn Kolibaba
Affiliations:
Compass Oncology, Vancouver Cancer Center,Vancouver,United States;US Oncology Research,The Woodlands,United States
,
Habte Yimer
Affiliations:
Texas Oncology-Tyler,Tyler,United States
,
John Burke
Affiliations:
Rocky Mountain Cancer Centers Aurora,Aurora,United States
,
Suzanne Fanning
Affiliations:
Prisma Health,Greenville,United States
,
Jay Courtright
Affiliations:
Texas Oncology-Dallas,Dallas,United States
,
Miguel Islas-Ohlmayer
Affiliations:
Oncology Hematology Care, Inc. Kenwood,Cincinnati,United States
,
Suman Kambhampati
Affiliations:
Sarah Cannon Cancer Institute, HCA Midwest Health, Research Medical Center,Kansas City,United States
,
Dingfeng Jiang
Affiliations:
AbbVie Inc.,North Chicago,United States
,
John Pesko
Affiliations:
AbbVie Inc.,North Chicago,United States
,
Tamas Vizkelety
Affiliations:
AbbVie Inc.,North Chicago,United States
,
Simon Sharmokh
Affiliations:
AbbVie Inc.,North Chicago,United States
,
Jacqueline Nielsen
Affiliations:
AbbVie Inc.,North Chicago,United States
Ian Flinn
Affiliations:
Sarah Cannon Research Institute-Tennessee Oncology,Nashville,United States
(Abstract release date: 05/14/20) EHA Library. Sharman J. 06/12/20; 294605; EP687
Jeff Sharman
Jeff Sharman
Contributions
Abstract

Abstract: EP687

Type: e-Poster

Background

The Bcl-2 inhibitor venetoclax (VEN) has demonstrated efficacy in patients (pts) with chronic lymphocytic leukemia (CLL). As VEN induces rapid cell death, pts with medium to high tumor burden (TB) are at greater risk for tumor lysis syndrome (TLS) and may require inpatient monitoring. 

Aims
Here, we explore tumor debulking prior to outpatient VEN initiation.

Methods

This single-arm, open-label phase 3b trial (NCT03406156) enrolled adult, untreated pts with CLL/SLL without 17p deletion, having medium to high TB. The study was planned to enroll 120 pts and included no formal statistical comparisons. Pts received at least 2 cycles (C) of debulking therapy (obinutuzumab [G] ± bendamustine [B]); TB was then reevaluated and pts who had not achieved low TB received additional debulking C (4 or 6 total). Subsequently, VEN therapy was initiated using a 5-wk ramp-up schedule, as VEN+G for 5 mo, then as VEN monotherapy until wk 53. An interim analysis was planned after 20 pts completed VEN ramp-up, to assess the safety of debulking and ramp-up regimens, and was reviewed by the data monitoring committee. Primary endpoints were to evaluate the reduction in TB after every 2 C of debulking, and IWCLL response rates.

Results

As of 2 Dec 2019, 110 pts were included; 76 received G and 34 G+B for debulking. The majority were <75 yr (85%) and male (66%). Medium (73%) and high TB (26%) at baseline (BL) was mainly driven by increased ALC, which was ≥25 × 109/L in 85% of pts. After C2, low TB was achieved in 87% (76/87) of evaluable pts; 92% (56/61) with G and 77% (20/26) with G+B. ALC decreased to <25 × 109/L after C2 in all pts with BL ALC ≥25 × 109/L on G (59/59) and G+B (18/18). The median decrease in lymph node size was 0.5 cm for G and 3 cm for G+B from BL to C2 and reduced further with more C of debulking. Grade (Gr) ≥3 adverse events (AEs) were observed more often during G+B (68%) than G (38%). Gr ≥3 AEs were similar during VEN phases (VEN+G/VEN mono; G: 33%/27%, G+B: 35%/27%), but the rate of VEN interruptions (G: 24%/17%, G+B: 31%/27%) and dose reductions (G: 6%/10%, G+B: 19%/18%) was higher for those debulked with G+B. AE of TLS was reported for 9/110 pts (8%) during debulking (G: 2 [clinical], G+B: 7 [5 lab/2 unclassified]) and 1/89 debulked pt (1%) with low creatinine clearance rate during VEN+G (lab).

Conclusion

Most pts achieved low TB at C2 of debulking with G±B prior to VEN ramp-up. AE of TLS was reported in 1 pt during VEN phase. Similar Gr ≥3 AEs were observed during VEN phases regardless of debulking agents. Debulking reduced TB and may facilitate outpatient VEN initiation.

Session topic: 06. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic lymphocytic leukemia, Hematological malignancy, Lymphoma

Abstract: EP687

Type: e-Poster

Background

The Bcl-2 inhibitor venetoclax (VEN) has demonstrated efficacy in patients (pts) with chronic lymphocytic leukemia (CLL). As VEN induces rapid cell death, pts with medium to high tumor burden (TB) are at greater risk for tumor lysis syndrome (TLS) and may require inpatient monitoring. 

Aims
Here, we explore tumor debulking prior to outpatient VEN initiation.

Methods

This single-arm, open-label phase 3b trial (NCT03406156) enrolled adult, untreated pts with CLL/SLL without 17p deletion, having medium to high TB. The study was planned to enroll 120 pts and included no formal statistical comparisons. Pts received at least 2 cycles (C) of debulking therapy (obinutuzumab [G] ± bendamustine [B]); TB was then reevaluated and pts who had not achieved low TB received additional debulking C (4 or 6 total). Subsequently, VEN therapy was initiated using a 5-wk ramp-up schedule, as VEN+G for 5 mo, then as VEN monotherapy until wk 53. An interim analysis was planned after 20 pts completed VEN ramp-up, to assess the safety of debulking and ramp-up regimens, and was reviewed by the data monitoring committee. Primary endpoints were to evaluate the reduction in TB after every 2 C of debulking, and IWCLL response rates.

Results

As of 2 Dec 2019, 110 pts were included; 76 received G and 34 G+B for debulking. The majority were <75 yr (85%) and male (66%). Medium (73%) and high TB (26%) at baseline (BL) was mainly driven by increased ALC, which was ≥25 × 109/L in 85% of pts. After C2, low TB was achieved in 87% (76/87) of evaluable pts; 92% (56/61) with G and 77% (20/26) with G+B. ALC decreased to <25 × 109/L after C2 in all pts with BL ALC ≥25 × 109/L on G (59/59) and G+B (18/18). The median decrease in lymph node size was 0.5 cm for G and 3 cm for G+B from BL to C2 and reduced further with more C of debulking. Grade (Gr) ≥3 adverse events (AEs) were observed more often during G+B (68%) than G (38%). Gr ≥3 AEs were similar during VEN phases (VEN+G/VEN mono; G: 33%/27%, G+B: 35%/27%), but the rate of VEN interruptions (G: 24%/17%, G+B: 31%/27%) and dose reductions (G: 6%/10%, G+B: 19%/18%) was higher for those debulked with G+B. AE of TLS was reported for 9/110 pts (8%) during debulking (G: 2 [clinical], G+B: 7 [5 lab/2 unclassified]) and 1/89 debulked pt (1%) with low creatinine clearance rate during VEN+G (lab).

Conclusion

Most pts achieved low TB at C2 of debulking with G±B prior to VEN ramp-up. AE of TLS was reported in 1 pt during VEN phase. Similar Gr ≥3 AEs were observed during VEN phases regardless of debulking agents. Debulking reduced TB and may facilitate outpatient VEN initiation.

Session topic: 06. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic lymphocytic leukemia, Hematological malignancy, Lymphoma

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