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DISMAL OUTCOMES OF PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA AFTER FAILURE OF BOTH INOTUZUMAB OZOGAMICIN AND BLINATUMOMAB
Author(s): ,
Walid Macaron
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Elias Jabbour
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Marina Konopleva
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Farhad Ravandi
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Nitin Jain
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Ghayas Issa
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Tapan Kadia
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Koji Sasaki
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Partow Kebriaei
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Musa Yilmaz
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Philip Thompson
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Koichi Takahashi
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Hussein Abbas
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
William Wierda
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Rebecca Garris
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Hagop Kantarjian
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
Nicholas Short
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
(Abstract release date: 05/12/22) EHA Library. Macaron W. 06/10/22; 357235; P372
Walid Macaron
Walid Macaron
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P372

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background

The development of novel monoclonal antibodies such inotuzumab ozogamicin (INO) and blinatumomab (Blina) results in superior response rates and survival in patients (pts) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). However, outcomes of pts after failure of both INO and Blina are not well-established, and effective treatment options for these pts are limited.

Aims

To determine response rates to subsequent therapies and overall survival (OS) in pts with R/R Philadelphia chromosome (Ph)-negative B-cell ALL after failure of both INO/Blina.

Methods

We conducted a retrospective analysis of outcomes in adult pts with Ph-negative B-cell ALL who relapsed or were refractory to both INO/Blina, at least one of which given as salvage therapy.

Results

The baseline characteristics of the 65 pts included are shown in Table 1. Of 29 pts with paired flow cytometry for CD19 and CD22 prior to receipt of either INO/Blina, 4 pts (14%) lost CD19 expression and 3 pts (10%) lost CD22 expression at time of INO/Blina failure.

After INO/Blina failure, 54 pts (83%) received subsequent therapy, with a median of 2 therapies (range, 1-6). Of 53 evaluable pts, 16 pts (30%) achieved CR/CRi with the first salvage therapy received after INO/Blina failure (CR=9%, CRi=21%), and 22 pts (42%) achieved CR/CRi with at least one salvage therapy (CR=17%, CRi=25%). Of the 22 responders, 16 pts (73%) achieved measurable residual disease (MRD) negativity by flow cytometry (sensitivity=0.01%) at best response. Nine responses (41%) were achieved with an investigational drug/regimen and 13 (59%) were achieved with commercial agent(s). Among 54 pts who received at least one subsequent therapy, 12 pts (22%) received CAR T-cells, and 9 pts (17%) proceeded to hematopoietic stem cell transplant (HSCT).

With a median follow-up of 22.3 months, the median OS from the time of INO/Blina failure for the entire population was 3.8 months, and the 1-year OS was 22% (figure 1A). Median relapse-free survival (RFS) was 3.5 months, with a 1-year RFS of 12%. Median duration of response (DOR) to subsequent therapy was 5.0 months, with a 1-year DOR of 17%. Median OS from INO/Blina failure in pts who received salvage therapy compared to those who did not were 4.7 months and 1.4 months, respectively (figure 1B). In the 9 pts who underwent HSCT, 2 (22%) are still alive and in continuous remission. The median OS from time of HSCT was 13.4 months,  and the 1-year post-HSCT OS was 59%. In the 12 pts who received CAR-T cells as a subsequent therapy, 6 (50%) responded and 2 were bridged directly to HSCT. The median OS from time of CAR T-cell therapy was 3.9 months, and the 1-year OS was 36%.

Outcomes of pts who received both INO and Blina as salvage therapy  (n=50), excluding those who received 1 of these agents in the frontline or MRD setting, were also analyzed. Median OS from the time of INO/Blina failure was 2.6 months. Thirty-nine (78%) of these 50 pts received subsequent therapy after INO/Blina failure. Of 38 evaluable pts, 15 pts (39%) achieved CR/CRi with at least one subsequent salvage therapy (CR=13%, CRi=26%). Median RFS and OS in pts who underwent subsequent therapy were 5.9 months and 3.9 months, respectively.

Conclusion

This study highlights the very poor outcomes of pts with R/R B-cell ALL after failure of both INO/Blina. For pts who respond to subsequent salvage therapy, a consolidative approach with SCT may improve outcomes. These data provide a historical reference for expected outcomes that may serve as a benchmark for the evaluation of novel drugs and combinations in the setting of INO/Blina failure.

Keyword(s): B cell acute lymphoblastic leukemia, Monoclonal antibody, Outcome, Survival

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P372

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background

The development of novel monoclonal antibodies such inotuzumab ozogamicin (INO) and blinatumomab (Blina) results in superior response rates and survival in patients (pts) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). However, outcomes of pts after failure of both INO and Blina are not well-established, and effective treatment options for these pts are limited.

Aims

To determine response rates to subsequent therapies and overall survival (OS) in pts with R/R Philadelphia chromosome (Ph)-negative B-cell ALL after failure of both INO/Blina.

Methods

We conducted a retrospective analysis of outcomes in adult pts with Ph-negative B-cell ALL who relapsed or were refractory to both INO/Blina, at least one of which given as salvage therapy.

Results

The baseline characteristics of the 65 pts included are shown in Table 1. Of 29 pts with paired flow cytometry for CD19 and CD22 prior to receipt of either INO/Blina, 4 pts (14%) lost CD19 expression and 3 pts (10%) lost CD22 expression at time of INO/Blina failure.

After INO/Blina failure, 54 pts (83%) received subsequent therapy, with a median of 2 therapies (range, 1-6). Of 53 evaluable pts, 16 pts (30%) achieved CR/CRi with the first salvage therapy received after INO/Blina failure (CR=9%, CRi=21%), and 22 pts (42%) achieved CR/CRi with at least one salvage therapy (CR=17%, CRi=25%). Of the 22 responders, 16 pts (73%) achieved measurable residual disease (MRD) negativity by flow cytometry (sensitivity=0.01%) at best response. Nine responses (41%) were achieved with an investigational drug/regimen and 13 (59%) were achieved with commercial agent(s). Among 54 pts who received at least one subsequent therapy, 12 pts (22%) received CAR T-cells, and 9 pts (17%) proceeded to hematopoietic stem cell transplant (HSCT).

With a median follow-up of 22.3 months, the median OS from the time of INO/Blina failure for the entire population was 3.8 months, and the 1-year OS was 22% (figure 1A). Median relapse-free survival (RFS) was 3.5 months, with a 1-year RFS of 12%. Median duration of response (DOR) to subsequent therapy was 5.0 months, with a 1-year DOR of 17%. Median OS from INO/Blina failure in pts who received salvage therapy compared to those who did not were 4.7 months and 1.4 months, respectively (figure 1B). In the 9 pts who underwent HSCT, 2 (22%) are still alive and in continuous remission. The median OS from time of HSCT was 13.4 months,  and the 1-year post-HSCT OS was 59%. In the 12 pts who received CAR-T cells as a subsequent therapy, 6 (50%) responded and 2 were bridged directly to HSCT. The median OS from time of CAR T-cell therapy was 3.9 months, and the 1-year OS was 36%.

Outcomes of pts who received both INO and Blina as salvage therapy  (n=50), excluding those who received 1 of these agents in the frontline or MRD setting, were also analyzed. Median OS from the time of INO/Blina failure was 2.6 months. Thirty-nine (78%) of these 50 pts received subsequent therapy after INO/Blina failure. Of 38 evaluable pts, 15 pts (39%) achieved CR/CRi with at least one subsequent salvage therapy (CR=13%, CRi=26%). Median RFS and OS in pts who underwent subsequent therapy were 5.9 months and 3.9 months, respectively.

Conclusion

This study highlights the very poor outcomes of pts with R/R B-cell ALL after failure of both INO/Blina. For pts who respond to subsequent salvage therapy, a consolidative approach with SCT may improve outcomes. These data provide a historical reference for expected outcomes that may serve as a benchmark for the evaluation of novel drugs and combinations in the setting of INO/Blina failure.

Keyword(s): B cell acute lymphoblastic leukemia, Monoclonal antibody, Outcome, Survival

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