DOSE REDUCED CHEMOTHERAPY IN COMBINATION WITH BLINATUMOMAB FOR NEWLY DIAGNOSED OLDER PATIENTS WITH PH-NEGATIVE B-PRECURSOR ALL: FIRST RESULTS OF THE BOLD TRIAL
Author(s): ,
Nicola Gökbuget
Affiliations:
Dept. of Medicine II, Hematology/Oncology,Goethe University, University Hospital,Frankfurt,Germany
,
Andrea Stoltefuß
Affiliations:
Hematology,Evang.Krankenhaus,Hamm,Germany
,
Stefan Schwartz
Affiliations:
Hematology,Charite Universitätsmedizin, CBF,Berlin,Germany
,
Andreas Viardot
Affiliations:
Hematology,Universitätsklinik ,Ulm,Germany
,
Lena Baumann
Affiliations:
Department of Medicine II, Hematology/Oncology,Goethe University, University Hospital,Frankfurt,Germany
,
Monika Brüggemann
Affiliations:
Hämatologie Labor Kiel,Universitätsklinikum Schleswig-Holstein,Campus Kiel,Kiel ,Germany
,
Christoph Faul
Affiliations:
Hematology,University Hospital,Tübingen,Germany
,
Maria Wachsmuth
Affiliations:
Hematology,University Hospital,Halle (Saale),Germany
,
Anne Wilke
Affiliations:
Dept. of Medicine, Hematology/Oncology,Goethe University, University Hospital,Frankfurt,Germany
,
Vladan Vucinic
Affiliations:
Hematology,University Hospital,Leipzig,Germany
Max Topp
Affiliations:
Hematology,University Hospital,Würzburg,Germany
EHA Library. Gökbuget N. 06/12/20; 294333; EP414
Dr. Nicola Gökbuget
Dr. Nicola Gökbuget
Contributions
Abstract

Abstract: EP414

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background

Older pts with ALL are ineligible for unmodified pediatric-based therapies. Even with age adapted, dose reduced regimens early death (ED) is considerable and overall survival (OS) poor. In 412 pts with a median age of 65 (55-85) yrs treated according to the GMALL Elderly Protocol we observed a CR rate of 75%, with 16% ED; the 3y OS was 30%. Thus, further intensification of chemotherapy is no option.

Aims
Therefore, the GMALL study group proposed a trial for the European Working Group for Adult ALL (EWALL) in order to evaluate Blinatumomab in combination with chemotherapy in older ALL pts (NCT 03480438) as a potential new standard for this patient group with high medical need. 

Methods
Pts aged 56 – 76 yrs with CD19-pos, Ph-neg B-precursor ALL are eligible. The primary endpoint of the trial is complete hematologic remission after induction i.e. chemotherapy and one cycle Blinatumomab, and the key secondary endpoint is molecular response. After a 5-d prephase with dexa (d1-5 10 mg/m2) and cyclo (d3-5 200 mg/m2) pts receive dexa, vincristine and idarubicin (induction I). Thereafter, pts with CR, CRu or PR receive one cycle Blinatumomab (28 ug/d, 28 d). Pts with failure to induction I are treated with induction II (cytarabine, cyclo) followed by Blinatumomab. A dose step after one week (9µg/d to 28µg/d) is scheduled in all pts starting Blinatumomab while not in CR/CRu. Consolidation treatment consists of alternating cycles of intermediate-dose methotrexate/PEG-asparaginase, intermediate-dose cytarabine and reinduction and 3 further cycles of Blinatumomab. This is followed by a maintenance therapy with 6-mercaptopurine/methotrexate up to a total treatment duration of 2 yrs. Pts receive repeated intrathecal prophylaxis. MRD is measured in the central reference laboratory in Kiel with quantitative PCR of clonal immunoglobuline /TCR rearrangements. 

Results

16 pts (pts) were included from 8 centers. The median age was 65.5 (56-76) yrs. 4 pts were older than 70 yrs (25 %). 7 pts (44 %) suffered from pro-B-ALL (N=3 MLL rearranged) and 9 pts from c-/pre-B-ALL. 7 pts had comorbidities (Charlson Score); most frequent were myocardial infarction (N=2), chronic pulmonary disorder (N=2) and diabetes (N=2). In one pt study treatment was terminated due to subdural hemorrhage in induction I. 14 pts were evaluable for induction I: 9 achieved CR/CRu (64%), 2 PR (14%), 2 failure (14%) and 1 ED due to sepsis (7%) was observed. 4/6 pts with proB and 5/8 pts with c/pre-B-ALL achieved CR. 12 pts were evaluable for the primary endpoint. 10 achieved CR (83%), 1 failure (8%) and 1 case of ED (8%) was counted. 

9/10 CR pts had an evaluable MRD assay: 5 had a complete MRD response, 2 had an MRD response (positive <10-4) and 2 remained positive but non quantifiable (pos nq). 5 CR pts with pro-B ALL were evaluable for MRD response. 1 had a molecular CR, 2 had an MRD response and 2 MRD pos nq. 4/ 4 CR pts with c/preB-ALL had a molecular CR. No unexpected adverse events of Blinatumomab were observed. At the time-point of analysis 15 pts are alive. 2 pts (both pro-B ALL) experienced a molecular relapse, one with subsequent hematologic relapse. The median follow-up is 6 (0-15) mo.  

Conclusion

Tolerability and efficacy of the regimen was promising with a high response rate and low mortality. MRD response was obtained in all pts with CR after induction. However, a proportion of pts – mainly pro-B- ALL - remained MRD positive. Further follow-up and larger patient numbers are required to establish the potential benefit of this regimen in all subtypes of B-prec. ALL.

 

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, Antibody, Treatment

Abstract: EP414

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background

Older pts with ALL are ineligible for unmodified pediatric-based therapies. Even with age adapted, dose reduced regimens early death (ED) is considerable and overall survival (OS) poor. In 412 pts with a median age of 65 (55-85) yrs treated according to the GMALL Elderly Protocol we observed a CR rate of 75%, with 16% ED; the 3y OS was 30%. Thus, further intensification of chemotherapy is no option.

Aims
Therefore, the GMALL study group proposed a trial for the European Working Group for Adult ALL (EWALL) in order to evaluate Blinatumomab in combination with chemotherapy in older ALL pts (NCT 03480438) as a potential new standard for this patient group with high medical need. 

Methods
Pts aged 56 – 76 yrs with CD19-pos, Ph-neg B-precursor ALL are eligible. The primary endpoint of the trial is complete hematologic remission after induction i.e. chemotherapy and one cycle Blinatumomab, and the key secondary endpoint is molecular response. After a 5-d prephase with dexa (d1-5 10 mg/m2) and cyclo (d3-5 200 mg/m2) pts receive dexa, vincristine and idarubicin (induction I). Thereafter, pts with CR, CRu or PR receive one cycle Blinatumomab (28 ug/d, 28 d). Pts with failure to induction I are treated with induction II (cytarabine, cyclo) followed by Blinatumomab. A dose step after one week (9µg/d to 28µg/d) is scheduled in all pts starting Blinatumomab while not in CR/CRu. Consolidation treatment consists of alternating cycles of intermediate-dose methotrexate/PEG-asparaginase, intermediate-dose cytarabine and reinduction and 3 further cycles of Blinatumomab. This is followed by a maintenance therapy with 6-mercaptopurine/methotrexate up to a total treatment duration of 2 yrs. Pts receive repeated intrathecal prophylaxis. MRD is measured in the central reference laboratory in Kiel with quantitative PCR of clonal immunoglobuline /TCR rearrangements. 

Results

16 pts (pts) were included from 8 centers. The median age was 65.5 (56-76) yrs. 4 pts were older than 70 yrs (25 %). 7 pts (44 %) suffered from pro-B-ALL (N=3 MLL rearranged) and 9 pts from c-/pre-B-ALL. 7 pts had comorbidities (Charlson Score); most frequent were myocardial infarction (N=2), chronic pulmonary disorder (N=2) and diabetes (N=2). In one pt study treatment was terminated due to subdural hemorrhage in induction I. 14 pts were evaluable for induction I: 9 achieved CR/CRu (64%), 2 PR (14%), 2 failure (14%) and 1 ED due to sepsis (7%) was observed. 4/6 pts with proB and 5/8 pts with c/pre-B-ALL achieved CR. 12 pts were evaluable for the primary endpoint. 10 achieved CR (83%), 1 failure (8%) and 1 case of ED (8%) was counted. 

9/10 CR pts had an evaluable MRD assay: 5 had a complete MRD response, 2 had an MRD response (positive <10-4) and 2 remained positive but non quantifiable (pos nq). 5 CR pts with pro-B ALL were evaluable for MRD response. 1 had a molecular CR, 2 had an MRD response and 2 MRD pos nq. 4/ 4 CR pts with c/preB-ALL had a molecular CR. No unexpected adverse events of Blinatumomab were observed. At the time-point of analysis 15 pts are alive. 2 pts (both pro-B ALL) experienced a molecular relapse, one with subsequent hematologic relapse. The median follow-up is 6 (0-15) mo.  

Conclusion

Tolerability and efficacy of the regimen was promising with a high response rate and low mortality. MRD response was obtained in all pts with CR after induction. However, a proportion of pts – mainly pro-B- ALL - remained MRD positive. Further follow-up and larger patient numbers are required to establish the potential benefit of this regimen in all subtypes of B-prec. ALL.

 

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, Antibody, Treatment

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