-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

53 Outcome of 841 Older Patients (>55 yrs) with Newly Diagnosed Ph/BCR-ABL Negative ALL Prospectively Treated According to Pediatric-Based, Age-Adapted GMALL Protocols

Program: Oral and Poster Abstracts
Type: Oral
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Management of Novel ALL Subsets in Different Age Groups
Saturday, December 10, 2022: 10:30 AM

Nicola Goekbuget, MD1, Andreas Viardot, MD2, Björn Steffen, MD1*, Joachim Hahn, MD3*, Bernd Spriewald, MD4*, Sonja Martin, MD5*, Simon Raffel, MD6, Lino L. Teichmann, MD7*, Arne Trummer, MD8*, Winfried Alsdorf, MD9*, Anke Morgner, MD10*, Stefan Schwartz, M.D.11*, Matthias Stelljes, Prof. Dr. med.12, Vladan Vucinic, MD13*, Nael Alakel, MD14*, Andrea Stoltefuß, MD15*, Claudia D. Baldus, MD16*, Monika Brüggemann, MD16*, Hubert Serve, MD1 and Dieter Hoelzer, MD, PhD17

1Department of Medicine II, Hematology/Oncology, Goethe University Hospital, Frankfurt, Germany
2Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
3Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany
4Med. Klinik 5 / Hämatologie u. Internist. Onkologie, Universität Erlangen-Nürnberg, Erlangen, Germany
5Department of Hematology and Oncology, Robert-Bosch-Hospital, Stuttgart, Germany
6Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
7Department of Medicine III, University Hospital Bonn, Bonn, Germany
8Department of Internal Medicine III, Braunschweig Municipial Hospital, Braunschweig, Germany
9Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
10Klinikum Chemnitz, Chemnitz, Germany
11Hematology, Oncology and Tumor Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
12Department of Medicine / Hematology and Oncology, University of Muenster, Muenster, Germany
13Department for Hematology, Cell Therapy and Hemostaseology, University of Leipzig Medical Center, Leipzig, Germany
14University Hospital TU Dresden, Germany, Dresden, Germany
15Evangelisches Krankenhaus Hamm, Hamm, Germany
16Department of Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, Kiel, Germany
17Onkologikum Frankfurt, Frankfurt, Germany

Outcome in younger patients (pts) with ALL has been improved considerably using intensive pediatric-based therapy, but limited data on this approach have been reported for older pts and even the age cut-off is heavily debated. The German Multicenter Center Study Group for Adult ALL (GMALL) has conducted a clinical trial (>55 years) (NCT00198978) which was followed by a registry trial based on standard management recommendations with prospective documentation in the GMALL registry (NCT02872987). Strategies were modified over the years (yrs). The backbone included: Pre-phase (Dexa, Cyclo), induction I (Dexa, VCR, Idarubicine), induction II (Cyclo, AraC), ±post-induction PEG-ASP, consolidation (C) cycles with IDMTX (± E.coli ASP), HDAraC (earlier: VM26), reinduction (VCR, Idarubicine, Cyclo, AraC), ± Rituximab in CD20+, i.th. prophylaxis and maintenance (6-MP/MTX) (group 1). The latest protocol (from 2017) additionally included IDMTX/PEG-ASP in consolidation and recommended MRD-based treatment modification (Blinatumomab in B-Lin and Nelarabin in T-Lin) in molecular failure (MolFail) after C2 (group 2).

882 patients (pts) from 142 sites were included 2003-2021 (table 1). 5% were withdrawn early and therefore not evaluable. The median age was 68 (56-86) yrs. 61% were older than 65 yrs. B-Lin-ALL was present in 68%; 7% of B-Lin-ALL (N=45) had a KMT2A-rearrangement. 19% and 9% had immature subtypes, pro-B and early T-ALL resp.. 50% had at least one comorbidity according to the Charlson-Score (ChS); 11% had a score ≥3; 28% had an BMI≥30 mg/m2. Group 2 vs group 1 had a significantly lower median age (66 vs 68 yrs; p=.001) and a higher proportion of T-ALL (21% vs 14%; p=.0003).

In 841 pts the CR rate after induction was 73% with 14% early death (ED) and 13% failure. The ED rate was lower in group 2 vs group 1 (9% vs 15%; p=.04). CR rates were 76%, 73% and 63% in three age groups (56-65, 66-75, ≥76 yrs) with ED rates of 9%, 14% and 26% resp. (p<.0001). CR rates were significantly lower in pts with WBC ≥30.000/µl (table 1). BMI (≥30 kg/m2) was not associated to CR/ED but ED rates were correlated to ChS with a high ED rate (26%) in those with ChS ≥3 (table 1).

MRD response data were available in 163, 239 and 173 pts after induction II, C1 and C2 resp. The molecular CR (MolCR)/ MolFail rates were 41%/52%, 57%/38% and 64%/30% resp. The remaining pts had intermediate MRD (MolIMR). MolCR rates were similar in B-Lin only (43%/58%/64%).

With a median follow up of 2.7 yrs overall survival (OS) in 841 pts at 3, 5 and 10 yrs was 36%, 28% and 22% resp. The 3y remission probability was 37%. Mortality in CR was 5% (3%, 6% and 7% by age) and 12% of the pts were withdrawn from protocol. OS strongly correlated to age and was very poor in pts older than 75 yrs (7% at 3 yrs; table 1). Only 8% (N=51) of all CR pts received an allogeneic stem cell transplantation (SCT) in CR1 (N=20 ≥65 yrs) but the SCT-rate increased in group 2 vs group 1 (9% vs 5%). 3y-OS after SCT in this selected group (N=51) was 56%.

OS was significantly superior in group 2 vs group 1 (50% vs 32%; p<0.001) (figure 1). This improvement occurred mainly in the younger age group (56-65 yrs): 62% vs 38% 3y OS in group 2 vs group 1 resp. (p<0.0001) with no significant improvement in pts older than 65 yrs. WBC and ChS≥3 were associated with poorer OS (table 1). MRD response had a significant impact on OS at all timepoints. Pts with MolCR after C1 had a 3 yr OS of 80% vs 52% for MolFail and 62% for MolIMR (p=.0004). Interestingly the 3y-OS of 52 MolFail pts tended to be superior in group 2 (74% vs 46%;p>.05). The CR rate and OS of MLL-rearranged cases was 62% and 19% resp..

With this age-adapted, pediatric-based regimen a reasonable CR rate was achieved up to 75 yrs. Pt numbers were small and OS very poor in pts >75 yrs. MolCR rates were overall lower compared to more intensive protocols in younger pts. Thus, treatment modification based on MolFail is a promising approach and might produce benefits in many older pts. The optimal time-point for treatment change remains to be defined. Together with more intensive consolidation including PEG-ASP this modification likely contributed to the improved outcome with 62% OS in the youngest cohort (56-65 yrs) in group 2. In all older pts, but specifically in those >65-75 yrs or with multiple comorbidities, alternative protocols with targeted therapies and further step-wise reduction of chemotherapy require prospective exploration in clinical trials with the major goal to reduce ED rate and to improve MRD response.

Disclosures: Goekbuget: Gilead/Kite: Other: Research funding (institution); invited talk; advisory board; Erytech: Other: Advisory board; Cellestia: Other: Advisory board; Incyte: Other: Research funding (institution); advisory board; Amgen: Consultancy, Other: Research funding (institution); invited speaker; advisory board; Pfizer: Consultancy, Other: Research funding (institution); invited speaker; advisory board; MorphoSys: Other: Advisory board; Jazz Pharmaceuticals: Other: Research funding (institution); advisory board; AstraZeneca: Other: Invited talk for company-sponsored symposia (with honoraria); AbbVie: Other: Research funding (institution); Novartis: Other: Research funding (institution); advisory board; Servier: Consultancy, Other: Research funding (institution); invited speaker; advisory board; Clinigen: Other: Advisory board. Viardot: Kite Gilead: Consultancy, Honoraria, Other: Support for meeting attendance; Novartis: Consultancy, Honoraria, Other: Support for meeting attendance; BMS: Consultancy, Honoraria, Other: Support for meeting attendance; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Other: Support for meeting attendance; Janssen-Cilag: Honoraria, Other: Support for meeting attendance; Astra Zeneca: Honoraria, Other: Support for meeting attendance; Incyte: Consultancy, Other: Support for meeting attendance. Steffen: Jazz Pharmaceuticals: Other: Travel/Congress Participation Support; AbbVie: Other: Travel/Congress Participation Support. Teichmann: Boehringer-Ingelheim: Honoraria; AOP: Honoraria; Sobi: Consultancy, Honoraria; Pfizer: Consultancy; BMS: Consultancy, Honoraria; Astellas: Consultancy; BeiGene: Other; Gilead: Other: n. Alsdorf: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Biontech: Other: Travel Grants, Research Funding. Schwartz: Amgen: Honoraria, Other: Advisory Board; CSI GmbH (Amgen/Jazz Pharmaceuticals): Speakers Bureau. Stelljes: MSD: Consultancy, Honoraria; Jazz: Honoraria; Kite: Consultancy, Honoraria; MSD Sharp & Dohme: Consultancy; Medac: Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding. Vucinic: Novartis, Gilead Kite, Takeda, MSD, BMS Celgene, Abbvie, Amgen: Honoraria; MSD, BMS Celgene, Novartis, Gilead Kite, Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi, BMS Celgene: Other: travel, accommodations, expenses. Alakel: Pfizer: Consultancy, Honoraria. Hoelzer: Amgen: Speakers Bureau; Paladin Labs: Speakers Bureau.

*signifies non-member of ASH