ALBERT

Description: Post-transplant lymphoproliferative disease (PTLD) remains an important complication of solid organ transplantation. For B-cell PTLD, current first line therapies are Rituximab monotherapy (R-Mono) or R-CHOP. However, optimal selection of initial treatment is challenging due to concerns about the relative efficacy and toxicity of these modalities, and because of uncertainty about the prognostic value of baseline factors. This retrospective study identified 72 biopsy-proven cases of PTLD, diagnosed between 2000 and 2012, from 4 UK centres. These included 34 liver, 32 renal and 6 cardiothoracic transplant recipients. The median age at histological diagnosis was 47 years (range 16 - 72 years) and 68% were male. The median time from transplant to diagnosis of PTLD was 93 months (range 2 – 302 months), with 83% of cases occurring after 1 year. Tumour histology included 14 polymorphic and 49 monomorphic lesions (including 34 diffuse large B-cell, 5 plasmablastic, 4 Hodgkin and 1 T-cell lymphomas) whilst in 9 cases the PTLD subtype was unspecified. EBV-association was noted in 39/72 (54%) and this was significantly related to disease presenting within a year of transplant (X2 p=0.004). Initial therapy was R-Mono in 16/72 (22%) and R-CHOP in 34/72 (47%). Selection of R-CHOP versus R-Mono was significantly associated with stage ≥3 disease (odds ratio [OR] 6.7, p=0.01), onset more than 1 year after transplant (OR 7.3, p=0.03), lack of EBV association (OR 0.1, p=0.002) and monomorphic versus polymorphic histology (OR 14.0, p=0.004). In a multivariate logistic model, advanced stage (OR 11.0, p=0.06) and monomorphic histology (OR 8.5, p=0.03) retained significance. Of patients who received R-Mono, 15/16 (94%) completed at least 4 infusions, with no treatment-related deaths. Of these, 4 patients subsequently received R-CHOP for consolidation of response (2 patients) or for relapsed / refractory disease (2 patients). Of those who received R-CHOP as initial therapy, 23/34 (68%) completed at least 6 cycles, with 4 treatment-related deaths. The overall response rate to R-Mono was 81% (10 CR [complete remission], 3 PR [partial remission] and 3 NR [no remission]), similar to that of R-CHOP at 74% (19 CR, 6 PR, 5 NR and 4 undetermined; X2 p=0.67). With a median follow-up of 38 months, survival outcomes for R-Mono and R-CHOP were 2 year Event-Free Survival of 62% and 54% (p=0.77), 2 year Progression-Free Survival of 67% and 58% (p=0.48) and 2 year Overall Survival (OS) of 74% and 59% (p=0.52; Figure 1A) respectively. Amongst all study patients, significant baseline predictors of (inferior) OS were age ≥50 years (HR 2.9, p=0.006), stage ≥2 disease (HR 4.9, p=0.003), ECOG performance status ≥2 (HR 2.1, p=0.05), and elevated LDH (HR 2.2, p=0.08 borderline significance). Extra-nodal disease, histology, EBV-association and time from transplant were not predictive. In multivariate analysis, age〉50 (HR 3.2, p=0.01) and advanced stage (HR 4.0, p=0.02) retained significance. Importantly, amongst those treated with R-Mono or R-CHOP, response to initial therapy was highly predictive of OS (overall response, HR 0.2, p

Description: Introduction: A recent phase I/II study of blinatumomab in children with relapsed/refractory B cell acute lymphoblastic leukaemia (B-ALL), found 39-51% achieved complete, often MRD negative, remission after two cycles of therapy. Higher responses were observed in patients with less than 50% bone marrow blasts, compared to greater than 50% (55.6% vs 32.7% (95% CI 30.8-78.5 and 20.3-47.1 respectively)1. Furthermore, an adult study showed complete minimal residual disease (MRD) response rates of 78% when blinatumomab was used to treat MRD-positive ALL in haematological remission 2. Hence response rates (and toxicity) to blinatumomab are highly correlated with pre-treatment disease burden. We present preliminary data showing an excellent response to blinatumomab in children and young adults with resistant B-ALL who had persistent MRD, or after debulking chemotherapy to achieve a partial remission. Methods: Eleven patients were identified through a national survey. The mean age of patients was 10 years (range 0.7-22 years, 3 infants and 1 Down syndrome ALL). All patients had B-lineage ALL which was CD19 positive. None had active CNS disease at the point of receiving blinatumomab. Prior to administration of blinatumomab, all patients either had persistent MRD following several courses of intensive chemotherapy or received debulking chemotherapy for heavier marrow infiltrates. Pre-blinatumomab chemotherapy to which the patients had failed to obtain an adequate MRD response included UKALL 2011 Regimens A or C, UKALL R3, Interfant 06 or NOPHO high risk blocks. Patients received 5-15 µg/m2 of blinatumomab for 1-2 cycles prior to definitive therapy. Results: Pre-blinatumomab, all patients except one were in morphological remission with MRD measurable by PCR (0.003-1%), the remaining patient had 9% marrow disease by morphology. After 1-2 cycles of blinatumomab all patients had negative MRD when measured by flow cytometry and/or by PCR, giving a 100% response rate. This was followed by Haemopoietic stem cell transplant (HSCT) in nine patients and the remaining two are awaiting transplant. Further data on patient characteristics, CNS status, relapse and survival outcome are being collected and will be presented at the meeting. Minimal toxicity was observed; of the seven patients in whom toxicity data were available, three had grade 1 CRS, which resolved spontaneously without interruption of therapy or treatment with corticosteroids or Tocilizumab. One patient reported grade 1 neurotoxicity. This preliminary UK experience demonstrates that excellent MRD response is observed with minimal toxicity in children and young adults who receive blinatumomab for persistent MRD or after debulking chemotherapy. This provided a bridge to transplant in patients who would otherwise not have benefited from the procedure because of persistent MRD. We are planning to extend these observations by undertaking a study of this strategy in first high-risk B-ALL relapse. Stackelberg Av, Locatelli F, Zugmaier G, et al. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. Journal of Clinical Oncology. 2016;34(36):4381-4389. Gokbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522-1531. Disclosures Ghorashian: Celgene: Other: travel support; Novartis: Honoraria. Marks:Novartis: Consultancy; Pfizer: Consultancy; Amgen: Consultancy. Vora:Amgen: Other: Advisory board; Novartis: Other: Advisory board; Jazz: Other: Advisory board; Medac: Other: Advisory board; Pfizer: Other: Advisory board.

Description: Background. Chemotherapy followed by ASCT is standard of care in fit transplant-eligible newly diagnosed patients with Multiple Myeloma (MM). Most patients, however, will relapse and require further treatment. With increasing choice of therapies at relapse, we need to understand the determinants of treatment outcomes for these patients, to aid management decisions and patient counselling. Methods. This was a retrospective analysis of sequential patients who relapsed from upfront ASCT carried out between 2000-2014. PFS1 was defined as time from ASCT to 1st progression or death; PFS2, time from ASCT to 2nd progression or death and 2nd PFS, time from start of salvage regimen to 2nd progression or death. Post relapse survival (PRS) was measured from progression date and overall survival (OS) from ASCT date. Disease response, and adverse FISH were assigned according to IMWG. Survival was estimated using Kaplan- Meier curves and correlative analysis by Cox regression models. Results. Of 474 patients undergoing ASCT (2000-2014), 277 relapsed with a median age of 58 years (range 29-70).The M:F ratio was 1.85:1. Isotypes identified were: IgG 57.0%, IgA 22.7%, light chain 15.9%. Median PFS1 from ASCT was 20 months (0.47-128.3). ORR pre-ASCT was 91.3% (sCR/CR 4.4%, VGPR 25.4%) and post ASCT was 95.3% (sCR/CR 14.5%, VGPR 52.2%). At relapse, median age was 60 years (30-73) and 36.5% of patients had ISS stage2-3 disease. For the 277 patients who relapsed, median OS from ASCT was 67 months (CI 57-73) and median PRS was 40 months (35-44). PFS1 had a strong influence on OS, HR 0.97 (95%CI: 0.96-0.97, p