PF173 RESULTS FROM UKALL60+, A UK PHASE 2 STUDY IN ELDERLY PATIENTS WITH UNTREATED ACUTE LYMPHOBLASTIC LEUKAEMIA
Authors: Morley N. , Kirkwood A. , Moorman A. , Clifton‐Hadley L. , Moreira L. , Rowntree C. , Wrench B. , Marwood E. , Patrick P. , Snowden J.A. , Marks D.I. , Fielding A.K. 
Published: June 2019

Background:

The outcome for older adults with acute lymphoblastic leukaemia (ALL) is unsatisfactory. Few studies have focussed entirely on older patients with ALL, despite an increasing incidence with age.

Aims:

To establish baseline expectations for CR, event free survival (EFS), OS and quality of life (QOL) measures for older patients of all ages and pre‐morbid states.

Methods:

UKALL60+ offered five ‘Pathways’ to be decided by investigator and patient choice (Table 1). Any patient with newly diagnosed ALL >60 years (or >55 and unfit for more intensive therapy) was eligible, with no exclusions for co‐morbidities, including concurrent malignancies. Baseline characteristics of each group including Charlson Comorbidity Index, ECOG, Karnofsky, IADL and CRASH scores were collected. The primary endpoint was CR rate after 2 phases of induction. Secondary objectives included EFS and OS, treatment related mortality and QOL.

Results:

From January 2013 to December 2018, 121 patients were recruited (5 excluded due to misdiagnosis) with a median age of 69 years (Range 55–83). Median follow up was 29.9 months (Range 1 day to 55 months). Table 1 shows treatment allocation by Pathway. Patients allocated the non‐intensive pathway D were significantly older (Median age of 73 cf. 67 years, p < 0.001) and more dependant (IADL score p = 0.04) but had non‐significant differences in co‐morbidities as assessed by CRASH score and Charlson index when compared with the Intensive Pathway B. Cytogenetics or FISH was attempted at diagnosis on 98 patients. The main abnormalities detected were as follows: t(9;22) = 26, t(4;11) = 2, other MLL = 2, low hypodiploidy/near‐triploidy = 14, complex karyotype = 2.

The Primary Endpoint of CR rate after 2 phases of induction by Pathway were A (Ph+ve) = 22/24 (92%), B Intensive) 33/48 (69%), C (Intensive+) 5/9 (56%), D (Non‐intensive) 8/18 (44%) and Pathway E 9/15 (60%). At a median follow up of 29 months EFS & OS by Pathway were; A 59% & 61%, B 57% & 71% C 40% & 53% and D 9% & 19%.

Grade 3/4 AEs were seen in the majority of patients. The most common toxicities were haematological and infections. The haematological and non‐haematological AE rate was similar in Pathway D to Pathways A‐C both for all AE's and grade 3/4 AE's.

Across all Pathways 48 patients have relapsed at a median of 11.4 months. To date 68 deaths have been reported; 52 patients died of ALL and 11 from infection. Non intensive Pathway D enabled patients to spend less time in hospital, particularly in Induction I, with an average of 15 inpatient days compared with 28.5 days for Pathway B (p = 0.002).

Summary/Conclusion:

Our study reflects the reality that treating ALL in older patients is a difficult balance between efficacy and toxicity. AE rates were high, as expected, but despite this the majority of patients who died did so from ALL. Age but not co‐morbidities as measured by Charlson and CRASH appears to be associated with choice of therapy. Patients treated on the non‐intensive pathway D, although spending less time in hospital had similar AE rates. They had a low CR rate and less than 20% 1 year EFS rate. Patients with Ph+ve disease had a higher CR rate but this did not translate into improved EFS or OS. We noted small numbers of longer‐term survivors and anticipate that forthcoming MRD and correlative science data will shed light on the correlates of good outcome in these persons. The UKALL60+ data will be invaluable as a baseline from which to develop more effective regimens including novel agents.

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