PDC is a practical, useful and relevant indicator of effective patient-doctor communication. A well-presented summary of existing levels of PDC is an effective intervention to improve PDC and, by inference, patient-doctor communication on health problems and treatments. PDC should also be examined and reported in prevalence and incidence studies based on patient's reports and doctor's records.

Chimeric antigen receptor (CAR) T-cell therapy is a new, effective treatment for patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukaemia (ALL). Tisagenlecleucel achieved a complete remission (CR) rate and minimal residual disease (MRD) negativity of 81% at 3 months in the pivotal study; overall survival (OS) was 76% at 12 months (Maude et al, 2018). Real world data confirmed similar outcomes, with 1-year OS of 77% and event free survival (EFS) of 52% (Pasquini et al, 2020). Relapse can occur in the form of CD19 negative or CD19 positive ALL. The latter is associated with lack of persistence of the CAR T product. B-cell aplasia (BCA) is an indirect measure of CAR T presence. Early (<6 months from infusion) loss of BCA is associated with high relapse risk (Pillai et al, 2019); therefore, allogeneic stem cell transplantation (SCT) is often considered. However, SCT is associated with therapy-related morbidity and mortality and not all patients will find a suitable donor. Therefore, the optimal management of patients with loss of BCA is yet to be defined. In our centre, we administered maintenance therapy to a cohort of children with early loss of BCA. When compared to UK patients undergoing SCT for the same indication, we noted promising early outcomes. We report the findings here. We collected data on children with r/r ALL treated with tisagenlecleucel at Great Ormond Street Hospital (GOSH) from January 2018 to January 2021 who presented loss of BCA without evidence of disease (negative molecular or flow cytometry MRD) within 12 months from infusion. Loss of BCA was defined as peripheral B-cell count ≥0.10 x 10^9/L or bone marrow (BM) CD19+ events ≥0.1%. We compared outcomes of children who received maintenance as per UKALL 2011 protocol at GOSH to those who received SCT for the same indication from all UK paediatric centres. Fourteen patients from GOSH met the inclusion criteria. Four had loss of BCA after 6 months from CAR T infusion, none of them received additional therapy and they are all alive and in CR at a median of 535 days after CAR T infusion (Figure 1, A and B). Ten patients recovered B cells at <6 months: 3 proceeded to SCT, 6 started on maintenance therapy, 1 received other treatment. In 2 cases, maintenance was commenced after a second CAR T infusion. Two patients from the UK cohort met the inclusion criteria for the SCT group. Analysis was performed on 6 children who received maintenance and 5 who had SCT. Baseline characteristics of the 2 groups were similar (male/female ratio, median age at infusion, cytogenetics). Time from infusion to loss of BCA did not differ: the median was 80 days (range 28-168) in children who had maintenance vs 93 days (range 28-150) in those who had SCT. At a median follow up of 511 days (range 222-812), 3/6 children who received maintenance relapsed at median 210 days after infusion and proceeded to further treatment, no patient relapsed post SCT. One child died of disease in the maintenance group 237 days after infusion, 2 children died of transplant related mortality in the SCT group at 222 and 422 days post infusion. OS and EFS did not differ statistically between the 2 groups, as shown in Figure 1 (C and D). We observed that outcome for patients who presented loss of BCA within or at 2 months from infusion was poor regardless of the intervention (maintenance or SCT). Management of patients who experience early loss of BCA after CAR T is challenging and there are little data to support optimal treatment. In our experience, maintenance therapy compared favourably with SCT with similar rate of OS and EFS. Of note, 2/5 patients died of TRM in the SCT group highlighting the toxicity of this approach in such heavily pre-treated patients. On the other hand, maintenance is a well tolerated, low-cost treatment which can be easily delivered on an out-patient basis. Our preliminary data support investigation of this strategy in larger, prospectively-recruited cohorts of patients. Moreover, our preliminary data suggest that the time of loss of BCA is a crucial clinical parameter, as children who developed it within 2 months from infusion had the worst outcome, possibly reflecting prior therapy intensity and its impact on autologous T cells. Figure 1 Figure 1. Disclosures Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.; Autolus: Patents & Royalties. Ghorashian: UCLB: Patents & Royalties: CARPALL; Novartis: Honoraria.

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Introduction: Immunotherapies like Inotuzumab ozogamicin (InO), Blinatumomab and Chimeric antigen receptor T cell therapy (CAR-T) have revolutionized outcomes in patients with Relapse/Refractory Acute Lymphoblastic Leukaemia (R/R ALL) with event free survival (EFS) of 50% at 1 year (Maude et al. 2018). Optimal phasing of these agents has not been clearly defined and depends on antigen expression on blasts, CNS status, T cell number and prior disease response. InO, a CD22 targeting antibody-drug conjugate has proven efficacy in adults (Kantarjian et al., 2016) and children as a bridge to allogeneic stem cell transplantation (allo-SCT) with a favourable toxicity profile (Brivio et al. 2021). However, outcomes following the use of InO prior to CAR-T therapy are still not established. This study provides a retrospective analysis of children and young adults who received InO as part of pre-CAR-T management (before leucapheresis or as bridging therapy to CAR-T infusion). Methods: Patients aged 0-25years with R/R ALL were eligible for the study if they received InO pre-CAR-T therapy. Retrospective data collection was performed using a standardised form from CAR-T centres in the UK. Response to CAR-T therapy and/or relapse was evaluated at 1, 3, 6, 12 months or at last follow-up. Results were compared to a control cohort of R/R ALL patients treated with tisagenlecleucel but without preceding InO, over a contemporaneous period, at the largest paediatric CAR-T centre in the UK. Results: Fourteen patients from 5 paediatric and young adult centres in the UK received InO after screening for CAR-T therapy. InO was used pre-leucapheresis, as bridging and for both in 2, 11 and 1 respectively. Two were excluded from outcome analysis (1 adolescent with Trisomy 21 and transfusion induced hepatic siderosis died due to VOD while awaiting CAR-T production and 1 failed CAR-T manufacture despite achieving an adequate T cell harvest as per manufacturer guidance). Twelve (85%) patients were able to receive CAR-T infusion at a median of 1 month (range 0.7-5.6 months) from first InO dose. InO was well tolerated with 21% developing febrile neutropenia and grade 4 cytopenias. Use of InO pre-leucapheresis led to successful manufacture of CAR-T cells in 2/3 (66%). InO group was compared with 27 children who received CAR-T without preceding InO over the same time period. Table 1 summarises patient and CAR-T characteristics of the two groups which were comparable. Median follow-up of the InO and non-InO groups was 10 months (range 2.8- 30.1 months). In the InO group(n=12), 3 (25%) remained leukemia free at last follow up. Nine patients (75%) relapsed. All relapses occurred within 6 months from CAR-T infusion. Seven (58%) of those who relapsed died at a median of 7.8 months post CAR-T infusion and 2 (16.6%) were salvaged with further therapy. Subsequent therapy (alternate CAR-T and/or allo-SCT) was carried out in 4/12 (33%) patients in the InO group and in 5/27 (18.5%) in the non-InO group (p= 0.2). EFS was significantly higher in the non-InO group (53% vs 12%, p=0.0009), as was OS (86% vs 13%, p=0.004) (Figure 1). Conclusion: This study provides a direct comparison between two contemporaneously treated cohorts with R/R ALL receiving CAR-T therapy. InO prior to CAR T cell therapy was well tolerated despite the cohort being heavily pre-treated except for one patient who developed fatal VOD prior to CAR T cell infusion. InO was given for disease debulking, rather than to achieve MRD negativity and hence majority of the cohort (75%) received only 1 dose of InO in bridging rather than the usual schedule of three doses weekly per cycle. Outcomes for the non-InO group were comparable to those treated on the ELIANA study but the OS of the InO group was significantly lower (13% vs 86% p= 0.004). Potential reasons include an impact of InO on function of CAR-T cells in vivo or a deleterious effect of InO on the B cell compartment such that CAR-T cells prove less effective. Due to the retrospective nature of the study, it is possible there was an inherent bias to use InO in patients with more resistant disease, although the very comparable pre CAR-T bone marrow disease burden in each group suggests this was not the case. The small size of the cohorts may also have exaggerated differences in outcome. Ultimately, randomised controlled studies of InO pre-CAR-T are required before firm conclusions about its impact on outcomes post CAR-T therapy can be ascertained. Figure 1 Figure 1. Disclosures Sharplin: Kite Gilead: Honoraria; Novartis: Other: Travel Support. Nicholson: BMS/Celgene: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees; Pfizer: Consultancy. Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.; Autolus: Patents & Royalties. Ghorashian: Novartis: Honoraria; UCLB: Patents & Royalties.

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