Characteristics and Outcome of Elderly Patients (&gt; 55 Years) with Acute Lymphoblastic Leukemia (ALL)
Authors: Wenge Daniela V. , Wethmar Klaus , Klar Corinna , Kolve Hedwig , Sauer Tim , Angenendt Linus , Evers Georg , Call Simon , Kerkhoff Andrea , Khandanpour Cyrus , Kessler Torsten , Mesters Rolf M. , Schliemann Christoph , Mikesch Jan-Henrik , Reicherts Christian , Brüggemann Monika , Berdel Wolfgang E. , Lenz Georg , Stelljes Matthias 
Published: November 2021

Abstract
Introduction: Prognosis of elderly ALL patients is generally considered to be poor. Nonetheless, data on disease characteristics, treatment and outcome of this group of patients is scarce.
Methods: Between May 2003 and October 2020, 96 patients (pts) aged &gt; 55 years with B-precursor ALL (91 pts) or T-ALL (5 pts), received first-line induction chemotherapy (84 pts) or were admitted for salvage treatment (8 pts) or allogeneic stem cell transplantation (alloSCT, 4 pts) at the University Hospital Muenster, Germany. 78 patients were diagnosed with a common-ALL (27 pts were BCR/ABL positive) and 13 patients with a pro-B-ALL. Age adapted BFM (Berlin-Frankfurt-Muenster)-like treatment regimens, according to the recommendations of the GMALL (German multicenter ALL study group) for younger (18-55 years, 25 pts) or elderly patients (&gt; 55 years, 68 pts) were used. In general, these protocols consisted of two cycles of induction therapy followed by consolidation, reinduction and consolidation therapy blocks in the 1 st year as well as a consecutive maintenance therapy in the 2 nd year. 3 patients (3%) received no intensive treatment due to poor performance status and comorbidities. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank-test and Cox proportional hazards model for RFS and OS, respectively.
Results: Median patient age at diagnosis was 66 years (range 55-89 years). 94% of all patients had an ECOG (Eastern Cooperative Oncology Group) status of 0-2 and 92% had a Charlson comorbidity index of 0-2. The median follow-up of all patients was 2.0 years (range 20 days - 16.9 years) and of surviving patients 3.7 years (range 8.8 months - 16.9 years). A complete remission (CR) after induction therapy was documented in 62 of 81 (77%) patients receiving their initial induction therapy at our center. Minimal residual disease (MRD) status was analyzed by quantitative real time PCR in 44 of these patients and 19 patients had an MRD negative CR (43%) after induction therapy. The rate of early death after intensive therapy (death within 100 days after start of treatment) was 6%. The 3 patients not treated with intensive chemotherapy died within 3 months.
27 of 93 patients finished the first year of treatment. Subsequent maintenance therapy was administered to 12 patients. The reasons for discontinuation of conventional treatment in the first and second year were relapsed disease (31 pts), alloSCT in 1 st CR (23 pts), toxicity/patients' preference (17 pts) and death in CR under conventional therapy (7 pts). 3 patients have not completed their therapy yet.
OS and RFS of the entire cohort at 1 year were 73% (95% CI: 64-82%) and 57% (95% CI: 47-67%) and at 3 years 46% (95% CI: 36-56%) and 32% (95% CI: 22-42%), respectively. The cumulative incidence of relapse at 1 and 3 years was 29% (95% CI: 20-41%) and 56% (95% CI: 45-69%), respectively. OS of those patients receiving an alloSCT (23 pts in 1 st CR, 7 pts in 2 nd CR, 3 pts with active disease, median age at alloSCT 62 years) at 1 and 3 years was 82% (95% CI: 68-95%) and 49% (95% CI: 32-67%), respectively. The cumulative incidence of relapse after alloSCT at 1 and 3 years was 16% (95% CI: 7-35%) and 32% (95% CI: 18-56%), respectively.
Regarding the entire patient cohort, older age (&gt; 75 years, 15 pts) was significantly associated with an inferior OS (p &lt; .001). BCR/ABL status, ALL phenotype (T- or B-ALL) or intensity of conventional treatment applied (protocol originally intended for patients ≤ 55 years vs &gt; 55 years) had no significant impact on OS. In multivariate analysis, ECOG status &gt;2 and persisting disease after 1 st consolidation therapy were risk factor associated with inferior OS (p &lt; .05).
Conclusion: Intensive treatment is feasible in selected elderly ALL patients (&gt; 55 years). High relapse rates and impaired survival rates underline the need for novel therapeutic strategies.

Disclosures
Khandanpour: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; BMS/Celgene: Honoraria. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Brüggemann: Incyte: Other: Advisory Board; Amgen: Other: Advisory Board, Travel support, Research Funding, Speakers Bureau; Janssen: Speakers Bureau. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Stelljes: Celgene/BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau.