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MINI-HYPER-CVD PLUS INOTUZUMAB OZOGAMICIN, WITH OR WITHOUT BLINATUMOMAB, IN OLDER ADULTS WITH NEWLY DIAGNOSED B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: UPDATES FROM A PHASE II TRIAL
Author(s): ,
Fadi Haddad
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Hagop Kantarjian
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Nicholas Short
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Farhad Ravandi
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Nitin Jain
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Walid Macaron
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Tapan Kadia
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Yesid Alvarado
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Naval Daver
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Gautam Borthakur
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Courtney DiNardo
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Marina Konopleva
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
William Wierda
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Jovitta Jacob
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Edith Roy
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Christopher Loiselle
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Anna Milton
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Juan Rivera
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
,
Rebecca Garris
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
Elias Jabbour
Affiliations:
Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Estados U
(Abstract release date: 05/12/22) EHA Library. Haddad F. 06/10/22; 357218; P355
Fadi Haddad
Fadi Haddad
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: P355

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background

Blinatumomab (Blina) and inotuzumab ozogamicin (INO) improve the outcomes of patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). These drugs may allow for use of less chemotherapy and improve remission durations and overall survival (OS) in older pts with newly diagnosed B-ALL.

Aims
To evaluate the combination of low-intensity chemotherapy and INO with or without Blina, in older pts with newly diagnosed B-ALL. 

Methods

Pts ≥60 years with newly diagnosed Philadelphia chromosome (Ph)-negative B-ALL were eligible to receive mini-hyper-CVD for up to 8 cycles. Initially, INO was given at 1.3-1.8mg/m2 on day (D) 3 of cycle 1 and 0.8-1.3mg/m2 on D3 of cycles 2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. POMP maintenance was given for up to 3 years. Starting with pt #50, the protocol was amended and INO was administered in fractionated doses with each of the 4 cycles of hyper-CVD (0.6 mg/m2 on D2 and 0.3 mg/m2 on D8 of cycle 1; 0.3 mg/m2 on D2 and 8 of cycles 2-4) followed by 4 cycles of blina. The cumulative doses of INO given before and after this amendment were 4.3 mg/m2 and 2.7 mg/m2, respectively. Maintenance was also amended to include 12 cycles of POMP and 4 cycles of blina (1 cycle of blina after every 3 cycles of POMP).

Results

80 pts have been treated with a median age of 68 years (range, 60-87); 30 pts (38%) were ≥70 years. 6 pts were in complete remission (CR) at enrollment and unevaluable for morphological response. Pt characteristics are summarized below (Figure 1A).

The overall response rate (ORR) among 74 evaluable pts was 99% (CR, n=66; CRi, n=7). MRD negativity by flow cytometry was achieved in 61/76 pts (80%) after 1 cycle and 74/79 pts (94%) overall. The 30-day and 60-day mortality rates were 0% and 3%, respectively. Among 79 pts who achieved remission, 33 (42%) are still in ongoing remission without stem cell transplant (SCT), 31 (39%) died in remission, 11 (14%) relapsed without SCT, and 4 (5%) proceeded to SCT in first remission (1 of whom subsequently relapsed). Notably, 9 pts (11%) later developed MDS/AML, 7 of whom had a TP53 mutation. Overall, 6 pts (8%) developed VOD, 1 after allogeneic SCT.

With a median follow-up of 55 months (range, 3-119), the 5-year continuous remission and OS rates were 76% and 47%, respectively (Figure 1B). Pts aged 60-69 years had better outcomes compared with pts 70 years (5-year OS rates: 59% vs 27%, respectively; P=0.04) and as did those without poor cytogenetics (i.e. complex, KMT2A-rearranged, low-hypodiploidy/near-triploidy) compared with poor cytogenetics (5-year OS rates: 54% and 25%, respectively; P=0.02). Deaths in remission were more frequent in pts ≥70 years compared with those 60-69 years (70% vs 35%; P=0.005). The 5-year OS rates for pts age 60-69 without poor-risk cytogenetics (n=37), age 60-69 with poor-risk cytogenetics (n=13), age 70 without poor-risk cytogenetics (n=24), and age 70 with poor-risk cytogenetics (n=6) were 69%, 39%, 36% and 0% respectively (Figure 1C). Presence of a TP53 mutation did not significantly impact OS (P=0.22).

Conclusion

Reduced-intensity chemotherapy plus INO, with or without blina, resulted in an ORR of 99% and a 5-year OS rate of 47% in older pts with newly diagnosed Ph-negative B-ALL. Outcomes were particularly favorable in those 60-69 years of age without poor-risk cytogenetics. Pts ≥70 years were at a higher risk of death in remission. A chemotherapy-free approach, with INO plus blina only, is therefore now being explored in this population.

Keyword(s): Acute leukemia, Acute lymphoblastic leukemia, B cell acute lymphoblastic leukemia, Phase II

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: P355

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background

Blinatumomab (Blina) and inotuzumab ozogamicin (INO) improve the outcomes of patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). These drugs may allow for use of less chemotherapy and improve remission durations and overall survival (OS) in older pts with newly diagnosed B-ALL.

Aims
To evaluate the combination of low-intensity chemotherapy and INO with or without Blina, in older pts with newly diagnosed B-ALL. 

Methods

Pts ≥60 years with newly diagnosed Philadelphia chromosome (Ph)-negative B-ALL were eligible to receive mini-hyper-CVD for up to 8 cycles. Initially, INO was given at 1.3-1.8mg/m2 on day (D) 3 of cycle 1 and 0.8-1.3mg/m2 on D3 of cycles 2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. POMP maintenance was given for up to 3 years. Starting with pt #50, the protocol was amended and INO was administered in fractionated doses with each of the 4 cycles of hyper-CVD (0.6 mg/m2 on D2 and 0.3 mg/m2 on D8 of cycle 1; 0.3 mg/m2 on D2 and 8 of cycles 2-4) followed by 4 cycles of blina. The cumulative doses of INO given before and after this amendment were 4.3 mg/m2 and 2.7 mg/m2, respectively. Maintenance was also amended to include 12 cycles of POMP and 4 cycles of blina (1 cycle of blina after every 3 cycles of POMP).

Results

80 pts have been treated with a median age of 68 years (range, 60-87); 30 pts (38%) were ≥70 years. 6 pts were in complete remission (CR) at enrollment and unevaluable for morphological response. Pt characteristics are summarized below (Figure 1A).

The overall response rate (ORR) among 74 evaluable pts was 99% (CR, n=66; CRi, n=7). MRD negativity by flow cytometry was achieved in 61/76 pts (80%) after 1 cycle and 74/79 pts (94%) overall. The 30-day and 60-day mortality rates were 0% and 3%, respectively. Among 79 pts who achieved remission, 33 (42%) are still in ongoing remission without stem cell transplant (SCT), 31 (39%) died in remission, 11 (14%) relapsed without SCT, and 4 (5%) proceeded to SCT in first remission (1 of whom subsequently relapsed). Notably, 9 pts (11%) later developed MDS/AML, 7 of whom had a TP53 mutation. Overall, 6 pts (8%) developed VOD, 1 after allogeneic SCT.

With a median follow-up of 55 months (range, 3-119), the 5-year continuous remission and OS rates were 76% and 47%, respectively (Figure 1B). Pts aged 60-69 years had better outcomes compared with pts 70 years (5-year OS rates: 59% vs 27%, respectively; P=0.04) and as did those without poor cytogenetics (i.e. complex, KMT2A-rearranged, low-hypodiploidy/near-triploidy) compared with poor cytogenetics (5-year OS rates: 54% and 25%, respectively; P=0.02). Deaths in remission were more frequent in pts ≥70 years compared with those 60-69 years (70% vs 35%; P=0.005). The 5-year OS rates for pts age 60-69 without poor-risk cytogenetics (n=37), age 60-69 with poor-risk cytogenetics (n=13), age 70 without poor-risk cytogenetics (n=24), and age 70 with poor-risk cytogenetics (n=6) were 69%, 39%, 36% and 0% respectively (Figure 1C). Presence of a TP53 mutation did not significantly impact OS (P=0.22).

Conclusion

Reduced-intensity chemotherapy plus INO, with or without blina, resulted in an ORR of 99% and a 5-year OS rate of 47% in older pts with newly diagnosed Ph-negative B-ALL. Outcomes were particularly favorable in those 60-69 years of age without poor-risk cytogenetics. Pts ≥70 years were at a higher risk of death in remission. A chemotherapy-free approach, with INO plus blina only, is therefore now being explored in this population.

Keyword(s): Acute leukemia, Acute lymphoblastic leukemia, B cell acute lymphoblastic leukemia, Phase II

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