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267 First Results of an Open Label Phase II Study to Evaluate the Efficacy and Safety of Inotuzumab Ozogamicin for Induction Therapy Followed By a Conventional Chemotherapy Based Consolidation and Maintenance Therapy in Patients Aged 56 Years and Older with Acute Lymphoblastic Leukemia (INITIAL-1 trial)

Program: Oral and Poster Abstracts
Type: Oral
Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Innovative Chemotherapy and Immunotherapy Strategies in Frontline and Relapsed Disease
Hematology Disease Topics & Pathways:
Clinically relevant
Saturday, December 5, 2020: 2:15 PM

Matthias Stelljes, MD1, Simon Raffel, MD2*, Ralph Wäsch3, Sebastian Scholl4*, Mustafa Kondakci, MD5*, Andreas Rank, PD Dr6*, Mathias Haenel, MD7*, Sonja Martin, MD8*, Katjana Schwab, MD9*, Julian Knaden10*, Klaus Wethmar, MD11*, Tim Sauer, MD12*, Wolfgang E. Berdel, Prof., MD13, Georg Lenz14, Martin Dugas15*, Monika Brüggemann, MD16*, Nicola Goekbuget, MD17 and Nael Alakel, MD18*

1Deptartment of Medicine A, University of Muenster, Muenster, Germany
2Department of Medicine V, University of Heidelberg, Heidelberg, Germany
3Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany
4Universitatsklinikum Jena, Jena, Germany
5Dept. of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
6Klinikum Augsburg, Augsburg, DEU
7Klinikum Chemnitz, Chemnitz, Germany
8Department of Hematology and Oncology, Robert-Bosch-Hospital, Stuttgart, Germany
9University of Bonn, Bonn, Germany
10University of Frankfurt, Frankfurt, Germany
11University Hospital Muenster, Muenster, DEU
12Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Baden-Württemberg, Germany
13Department of Medicine A, University Hospital Muenster, Muenster, Germany
14Department of Medicine A, University Hospital Muenster, Munster, Germany
15Institute of Medical Informatics, Universitiy of Muenster, Münster, DEU
16Department of Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, Germany
17University Hospital, Department of Medicine II, Hematology/Oncology, Head of Study Center Depart of Medicine II, Hematology/Oncology Goethe University Hospital, Frankfurt, Germany
18University Hospital, Dresden, Germany

Introduction: Acute lymphoblastic leukemia (ALL) represents around 5% of all newly diagnosed leukemia in patients between 55 and 70 years of age. Despite recent advances especially in younger patients, the prognosis of older patients with ALL remains dismal, even after moderately intensive chemotherapy. Due to increasing toxicity and infection rates in older patients, dose intensification of induction treatment often is no justifiable option. Consequently, new treatment options are needed to improve the survival of older ALL patients.

Methods: This open label phase II study of the German Multicenter Study Group on Adult Acute Lymphoblastic Leukemia (GMALL) is currently activated in 14 centers in Germany. Patients aged >55 years with newly diagnosed acute B lymphoblastic leukemia, with the exception of Philadelphia-chromosome or BCR-ABL positive ALL
or Burkitt’s or mixed phenotype acute leukemia, are eligible. Leukemic blasts must have CD22 surface expression of at least 20%. No previous ALL-specific treatment, with the exception of corticosteroids and/or single dose vincristine and/or up to 3 doses of cyclophosphamide (cycloph.) plus standard prephase treatment are allowed. The 1st induction cycle consists of inotuzumab ozogamicin (InO) 0.8 mg/m2 on day1 and 0.5 mg/m2 on days 8 and 15 together with dexamethasone 10 mg/m2 (days 7-8, days 14-17) and 1 intrathecal injection of methotrexate (MTX), cytarabine (AraC) and dexamethasone (Dexa). The 2nd and 3rd induction cycle consist of InO 0.5 mg/m2 on days 1, 8 and 15 plus intrathecal injection of MTX/AraC/Dexa. Response evaluation is scheduled after each cycle. Patients achieving a complete remission are offered to receive 5 conventional consolidation therapies (3 x ID-MTX/asparaginase; 2 x ID-AraC) and one reinduction therapy (idarubicine/AraC/cycloph./Dexa) in combination with rituximab (for CD20+ ALL), followed by a maintenance therapy with 6-mercaptopurine/MTX. The primary endpoint is is event free survival (EFS) at 12-months follow-up. An event is any of the following: persisting bone marrow blasts after 2 cycles of InO, relapse or death. An event rate of ≤40% at 12 months follow-up is considered to qualify the experimental treatment as very promising for additional testing. Under the assumption of one-sided type I error of 5% and 80% power, 42 evaluable patients were needed for primary endpoint analysis. The INITIAL-1 trial is registered with ClinicalTrials.gov, identifier: NCT03460522.

Results: As of July 2020, 31 patients have been included, with induction results available for 29 patients. Median age at initial diagnosis was 64 years (range 56-80 years). Twenty-five patients were diagnosed with a common- and 4 with a pro-B lymphoblastic leukemia. Median CD22 expression on leukemic blasts was 70% (range 21-99%). Due to suspected therapy related liver toxicities, 1 patient received 1 induction cycle and 1 patient 2 induction cycles (both were in remission after the 1st induction). All other patients completed induction therapy and achieved complete remission (CR/CRi) mainly after the 1st induction. Results of minimal residual disease (MRD) measured by PCR are available for 23 patients, with 17 being MRD-negative after induction. So far, 4 events have been reported (2 deaths in remission and 1 relapsed ALL in the 1st year of treatment; one relapsed disease in the 2nd year). With a median follow-up of 242 days, the probability of OS at 1 year is 82.4 %. Two patients received an allogeneic stem cell transplantation in ongoing 1st remission. With regard to adverse events (AEs) during induction therapy 1, 2 and 3, most common AEs ≥CTC 3 reported were leukocytopenia (in 64%, 33% and 13% of all cases, respectively), anemia (54%, 28%, 13%), thrombocytopenia (68%, 17%, 26%) and elevation of liver enzymes (31%, 22%, 20%).

Conclusion: Replacement of conventional induction chemotherapy by InO is feasible, results in promising remission rates, and may reduce the risk of early morbidity and lethality, particular in older patients with acute B lymphoblastic leukemia.

Disclosures: Stelljes: Amgen: Consultancy, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau. Wäsch: Pfizer: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Haenel: Amgen, Novartis, Roche, Celgene, Takeda, Bayer: Honoraria. Lenz: Nanostring: Consultancy; Morphosys: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Verastem: Research Funding; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy; AQUINOX: Research Funding; Agios: Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding; BMS: Consultancy; Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Brüggemann: Affimed: Research Funding; Regeneron: Research Funding; Celgene: Consultancy; Roche: Consultancy; Incyte: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Goekbuget: Gilead: Consultancy; Kite: Consultancy; Servier: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Erytech: Consultancy; Amgen: Consultancy, Research Funding. Alakel: Pfizer: Consultancy.

OffLabel Disclosure: Inotuzumab ozogamicin for induction therapy (1st line therapy)

*signifies non-member of ASH