Health-Related Quality of Life in Adolescents and Young Adults Treated with Blinatumomab Consolidation for CD19+ Ph-Negative Acute Lymphoblastic Leukemia in the Australasian Lymphoma and Leukaemia Group (ALLG) ALL09 “Sublime” Study

Introduction The impact of blinatumomab on the health-related quality of life (HRQoL) of adolescents and young adults (AYA) in the treatment of de novo acute lymphoblastic leukemia (ALL) has not previously been reported. The phase II ALL09 “SuBliME” study showed the substitution of chemotherapy by blinatumomab in the consolidation phase of a BFM based protocol improved day 79 minimal residual disease (MRD) negativity rates and resulted in excellent 2-year disease free and overall survival. We present the patient-reported HRQoL in participants from ALL09. Methods Study participants were treated with a conventional 4-drug induction, followed by a 28-day infusional blinatumomab consolidation (together with intrathecal methotrexate) planned to commence at day (d) 36, and be completed by d64. HRQoL was assessed at screening and at the end of each treatment phase, sequentially for the duration of the study, with study participants following protocol-driven treatment pathways. The timepoints presented here (screening, d36, d64), are most representative of the impact of blinatumomab on HRQoL without dilution from subsequent treatments in the study protocol. Change in HRQoL scores at d36 (end of induction) or d64 (end of blinatumomab consolidation) are presented relative to corresponding mean scores at screening (baseline). Overall HRQoL was assessed using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) trial outcome index (TOI); this is a composite of the FACT-Leu (Leukemia specific score) + FACT-G Physical + Functional scales. FACT-G Physical and Emotional scores, and the FACT-GOG NTX, the neurotoxicity specific scale, are also presented. The mean change in HRQoL score from screening to d36 and d64 was tested for equality to zero with the paired t-test. Results Fifty-five participants with a median age of 25 years (range 16 to 39) were enrolled from April 2019 to April 2022 and followed for a median of 61.5 months (range 53-78 months). 54.5% (30/55) were male; performance status ECOG 0/1 96% (53/55). Questionnaire completion rates were high: 98% (54/55) at screening, 89% (49/55) at d36, and 87% (48/55) at d64. FACT-LEU TOI [Mean 76.77, SD 16.93] did not change significantly from baseline to d36 (p=.54), but at d64 had improved significantly to +9.82 [SD 17.45] above baseline (p<.001). The constituents of this score were as follows: the FACT-LEU score which includes Leukemia-specific items addressing systemic symptoms, fatigue, infection, and uncertainty regarding the future, was 42.36 [SD 10.31] at baseline, +1.30 [SD 9.22] at d36 (p=.33), but at d64 had improved significantly above baseline [+6.84, SD 9.18] (p<.001); FACT-G Physical wellbeing significantly deteriorated by -2.14 [SD 5.38] (p=.008) at d36 from a mean of 20.43 [SD 5.57] at baseline, and significantly improved +2.31 (SD 6.33) above baseline by d64 (p=.015); and FACT-G-Functional wellbeing which relates to work, sleep and general enjoyment, did not significantly change at d36 (p=.54) or d64 (p=.46). FACT-G Emotional wellbeing score (relating to coping with illness, worsening condition, and dying) improved by +1.69 [SD 4.27] (p=.008) by d36, and +2.17 (SD 3.69; p<.001) by d64. FACT-G Social wellbeing (family, friend support, family acceptance of illness, sexuality) score at d36 did not change significantly from baseline [-0.66, SD 3.95] (p=.25), but significantly deteriorated -2.00 [SD 3.54] below baseline (p<.001) at d64. FACT-GOG NTX, encompassing neurotoxicity-related questions, deteriorated significantly at d36 by -5.10 [SD 8.32] from screening (p<.001), but at d64 had returned to baseline levels [-0.90, SD 8.72] (p=.47). Conclusions This is the first study to report the effect of blinatumomab on the HRQoL of AYA patients treated as part of induction/consolidation for de novo CD19+ Ph negative ALL. Blinatumomab consolidation was associated with an improved FACT-Leu TOI at d64 versus screening or end of induction at d36, but reduced FACT-G Social. These findings support the use of blinatumomab in the de novo setting but suggest the need to investigate psychosocial interventions that may improve the social wellbeing of patients during consolidation. Future studies will explore whether targeted changes in protocol design can improve HRQoL measures in adolescent and adult patients with de novo ALL.