ALBERT

Description: Background: Despite the availability of new therapies for acute lymphoblastic leukemia (ALL), older patients have historically poor responses to treatment and poor outcomes versus younger patients, with 5-year survival rates of approximately 20% or less. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that redirects cytotoxic T cells to lyse CD19-positive B cells and is approved for the treatment of relapsed or refractory (r/r) B-cell precursor (BCP) ALL and for minimal residual disease-positive ALL in the US. In the phase 3 TOWER study in patients with r/r Philadelphia chromosome-negative (Ph-) BCP ALL who received blinatumomab compared with standard-of-care (SOC) chemotherapy, overall survival was improved (median, 7.7 vs 4.0 months; P=0.01; Kantarjian H, et al. N Engl J Med. 2017;376:836-847), and posttreatment health-related quality of life (HRQoL) across all EORTC QLQ-C30 scales was better (Topp MS, et al. Blood. 2018;131:2906-2914). TOWER efficacy results did not differ by age group. In this subgroup analysis of TOWER, we assessed the HRQoL of older patients versus younger patients who received blinatumomab or SOC chemotherapy. Methods: Patients (N=405) with r/r Ph- BCP ALL were randomized 2:1 to receive 2 cycles of induction blinatumomab by continuous intravenous infusion (n=271) or SOC (n=134). Patients could receive transplant at any time following cycle 1. Those in remission could receive up to 3 consolidation cycles; 12 months of maintenance was allowed for those who received up to 3 consolidation cycles and had bone marrow response. HRQoL was assessed using the EORTC QLQ-C30 Questionnaire on days 1 (baseline), 8, and 15, on day 29 of cycle 1; day 1, 15, and 29 of each consolidation cycle; and at the safety follow-up. The questionnaire included 1 global health status scale, 5 functioning scales, 3 symptom scales, and 6 single-symptom items. For global health status and functioning scales, a higher score indicates better HRQoL; for symptom scales/items, a lower score indicates better HRQoL. A 10-point change was viewed as the minimum clinically important difference in EORTC QLQ-C30 (Zikos E, et al. EORTC. 2016). In this analysis, HRQoL in TOWER was assessed using two different age cutoffs:

Description: Background: Proteasome inhibitors (PIs) are a highly active drug class in multiple myeloma (MM), but development of resistance is commonly observed. Although all clinical-stage PIs are effective inhibitors of chymotrypsin-like (CT-L) proteasome subunit activity, a possible mechanism of resistance is compensatory hyperactivation of the caspase-like (C-L) and trypsin-like (T-L) subunits. Marizomib (MRZ) is a novel, irreversible, second-generation PI under development for the treatment of MM and malignant glioma. MRZ potently inhibits the 3 subunits of the 20S proteasome with a specificity and activity distinct from that of bortezomib and carfilzomib and their oral analogs ixazomib and oprozomib. Methods: In the clinical study NPI-0052-102, we evaluated the pharmacodynamic (PD) activity of MRZ against all three proteasome subunits in whole blood after single, or repeated administration, via two schedules in patients (pts) with previously treated advanced malignancies (solid tumors or hematologic). Pts received MRZ via Schedule A - weekly dosing for 3 doses in 4-week cycles by IV infusion over 1 to 10 min, or Schedule B - twice-weekly dosing for 4 doses in 3-week cycles by IV infusion over 10 min to 2 hr. Blood samples were collected on Days 1 and 15 (Schedule A) or 1 and 11 (Schedule B), pelleted by centrifugation and frozen within 48 hrs. Pellets were lysed and the activity of all 3 proteasomal subunits was assayed using specific fluorogenic substrates. Results: Partial or complete inhibition of all three proteasome subunits was achieved with both once-weekly and twice-weekly MRZ dosing. The rank order of sensitivity, CT-L 〉 T-L 〉 C-L, was as expected from the biochemical and cellular potencies of the drug. For CT-L activity, proteasome inhibition was dose dependent, with both the initial effect (on Cycle 1, Day 1 - C1D1) and the peak effect of proteasome inhibition increasing in a dose-dependent manner. CT-L inhibition was modest at the lowest dose levels (≤ 0.15 mg/m2), reaching moderate levels after repeat dosing. At intermediate dose levels of 0.3 to 0.55 mg/m2, CT-L inhibition was 31% to 75% on C1D1, rising to 70% to 93% after repeat dosing. At doses of 0.7 mg/m2 and above, inhibition of CT-L activity was usually complete within the first cycle. By contrast, C-L and T-L activities were unchanged or increased in the first cycle, suggesting compensatory hyperactivation in response to effective blockade of CT-L activity. Importantly, however, this response was overcome by repeat dosing with MRZ, and inhibition of T-L and C-L activity was noted across all dose levels. For C-L activity, treatment with MRZ at the recommended Phase 2 dose (RP2D) of 0.5 mg/m2 with twice-weekly dosing resulted in inhibition of up to 39% by Cycle 2 and was maintained, when tested, through Cycles 4 and 6. Treatment at the RP2D of 0.7 mg/m2 for once-weekly dosing resulted in C-L inhibition of 14% to 37% by the end of the first cycle, rising to 31% to 50% by the end of Cycle 2. Blockade of T-L activity was more robust after multiple cycles of MRZ therapy. Although inhibition of the T-L subunit was absent on C1D1 in patients receiving 0.5 to 0.55 mg/m2, inhibition of up to 80% was achieved by Cycle 2 and maintained for the duration of treatment. At the once-weekly RP2D of 0.7 mg/m2, T-L inhibition of 29% to 56% was achieved by the end of the first cycle, rising to 64% to 78% by the end of Cycle 2. Conclusions: The PD activity of MRZ against all three proteolytic subunits was assessed in patients with MM, solid tumors, and advanced lymphomas. At the twice-weekly and once-weekly RP2Ds, complete inhibition of CT-L activity was observed within 1-2 cycles of therapy, but accompanied by compensatory hyperactivation of the C-L and T-L subunits. This phenomenon in red cells suggests that it may be due to allosteric interactions within the catalytic core of the 20S proteasome rather than de novo synthesis of additional proteasomes. Ongoing MRZ therapy was able to overcome this adaptive response, resulting in robust pan-subunit proteasome inhibition within 2-6 cycles, most probably due to the cumulative effect of multiple exposures to MRZ. Due to their reversible binding mode (bortezomib, ixazomib) or monospecificity for the CT-L site (carfilzomib, oprozomib), other clinical PIs are predicted to lack this capability. This unique property of MRZ may explain in part its clinical activity in patients with MM resistant to both bortezomib and carfilzomib. Disclosures Off Label Use: marizomib treatment for multiple myeloma and solid tumours.. Harrison:AbbVie: Research Funding; Janssen: Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Burrows:Triphase Accelerator Corporation: Consultancy. Reich:Triphase Accelerator Corporation: Consultancy. Trikha:Triphase Accelerator Corporation: Employment.

Description: Abstract 4143 AIM: Fludarabine Melphalan (FluMel) is the commonest Reduced Intensity Conditioning (RIC) regimen used in Australia and New Zealand. This study aims to assess the relative benefit of this regimen in both lymphoid and myeloid malignancies and to further delineate risk factors associated with an improved survival using RIC conditioning. METHOD: This was an ABMTRR based retrospective study assessing the outcome of FluMel RIC allografting in 9 Australian and New Zealand Centres between 1998 and 2008. Data was collected from centres using an excel based eCRF emailed to centres. Analysis was performed using Stata software and a p value less than 0.05 was considered significant. RESULTS: Median follow up was 3.4 years. There were 342 patients with a median age of 54 years (18–68) and 61% were male. 234 patients had myeloid malignancies with AML (n=166) being the commonest indication whereas there were 110 lymphoid patients with NHL (n=64) the main indication. TRM at D100 was 14% with no significant difference between the groups. OS and DFS were similar between myeloid and lymphoid patients (50% and 43% at 5 years respectively). There was no difference in the cumulative incidence of relapse and GVHD between the groups. Multivariate analysis revealed 4 adverse risk factors for DFS: non-HLA identical sibling donor, not in remission at transplant, previous autologous transplant, and recipient CMV +ve. The presence of Chronic GVHD was associated with a better DFS predominantly due to a marked reduction in relapse (HR 0.44, p=0.003). CONCLUSION: This is one of the largest analyses of Fludarabine Melphalan RIC transpants performed. This dataset confirms that FluMel provides durable remissions in both myeloid and lymphoid malignancies with 50% overall survival at 5 years. The multivariate analysis provides important clues for improving outcomes when planning FluMel conditioning in patients with haematological malignancies. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Blinatumomab, a bispecific T-cell engager antibody construct, binds specifically to CD19 (B cells) and CD3 (T cells) to facilitate lysis of CD19-positive target B-lineage cells. Based on a single-arm phase 2 study, blinatumomab received approvals in the US (accelerated) and EU (conditional) for the treatment of Philadelphia chromosome-negative (Ph-) relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the phase 3, randomized, open-label TOWER study, blinatumomab immunotherapy significantly improved overall survival (OS) as compared to SOC chemotherapy in adult patients with Ph- r/r BCP-ALL. This abstract reports the impact of blinatumomab compared with SOC on HRQoL using data from TOWER. Methods Patients (n=405) with r/r BCP-ALL were randomized 2:1 to receive either blinatumomab (n=271) or SOC chemotherapy (n=134). Patients in remission after 2 induction cycles were eligible to continue therapy. A 12-month maintenance phase was allowed for patients who received up to 3 consolidation cycles and continued with a bone marrow response. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) on day 1 (baseline), day 8, day 15, day 29 in each cycle of investigational therapy and safety follow up. The HRQoL analyses included subjects with baseline and ≥1 post-baseline result of any EORTC QLQ-C30 multi-item scale or single-item measure. The change from baseline was summarized by visit and by treatment arm. Time-to-deterioration (TTD) analyses were conducted to determine the treatment effect based on timing from the initiation of treatment to a 10-point deterioration from baseline in HRQoL using EORTC QLQ-C30 or time to an event free survival (EFS) event. EFS was defined as day 1 for subjects who never reached hematologic response, and as time to relapse following response or death for those who reached hematologic response. Results Of the 376 patients who received at least 1 dose of study drug, 342 patients had baseline and ≥1 post-baseline HRQoL results. Mean pre-treatment baseline scores were balanced between the blinatumomab (n=247) and SOC (n=95) groups. In general, patients receiving blinatumomab had better post-treatment HRQoL versus SOC across all multi-item scales or single-item measures based on visual inspection (Table1). As early as day 8 of cycle 1 in the SOC arm, mean changes from baseline suggested worsening in HRQoL in almost all subscales/single items, whereas in blinatumomab arm, mean changes from baseline suggested improvement in HRQoL in almost all subscales (Table 1). The hazard ratios (HRs) from the TTD analyses ranged from 0.588 to 0.798 in favor of blinatumomab, with the upper bounds to the 95% CI

Description: Key Points Blinatumomab delays deterioration in HRQL in adults with R/R ALL.

Description: Background Dysregulation of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway signaling has been implicated in the pathogenesis of lymphoma. SAR245409 is a potent inhibitor of class I PI3K isoforms (α, β, γ and δ) and also inhibits mTORC1 and TORC2. In the phase 1 dose-expansion cohort of study TED11440 (NCT00485719), SAR245409 showed promise in several lymphoma subtypes: 1 complete response (CR) in a transformed lymphoma and 2 partial response (PR) [1 diffuse large B cell lymphoma (DLBCL) and 1 mantle cell lymphoma (MCL)] and 3 patients with stable disease (SD) longer than 3 months [1 follicular lymphoma (FL), 1 MCL and 1 Hodgkin Lymphoma] (Papadopoulos et al. ASH 2011). The Sanofi sponsored study ARD12130 (NCT01403636) is an ongoing multicenter, multinational, open-label, phase 2 study of SAR245409 in patients with lymphoproliferative malignancies enrolling on 4-arms: FL, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), MCL and DLBCL. Preliminary Stage 1 results from FL patients (pts) are reported. Methods Eligible pts for the FL arm had relapsed or refractory FL (Grade 1, 2, or 3a) with no clinical suspicion of transformation to an aggressive subtype and who had received ≥2 but ≤ 6 prior chemotherapy regimens. Pts were treated with SAR245409 at 50 mg twice daily orally until disease progression or withdrawal for other reasons including toxicity. Tumor response was based on modified International Working Group response criteria. A Simon 2-stage design was used to evaluate the primary efficacy endpoint of objective response rate (ORR) in the FL arm; if at least 6 of the first 24 evaluable patients in Stage 1 achieved an objective response (OR), the study would continue to Stage 2 with a total of 45 evaluable patients. If 14 or greater total patients among the 45 total evaluable achieved OR, the null hypothesis would be rejected. Results Twenty-eight FL patients were enrolled to stage 1. Median age was 62 years (range 38-87 years), 60% were males, 78% of pts had stage III/IV disease and 64% had received ≥ 3 prior lines of treatment. At data cutoff (end of March 2013), 15/28 (54%) pts had discontinued treatment: 10 due to disease progression, 2 due to adverse events (AEs) (grade 2 pneumococcal pneumonitis and grade 3 diarrhea), 2 due to consent withdrawal, and 1 due to non-compliance. Median treatment duration was 32 weeks (range 4-72 weeks). Among the first 24 evaluable patients in the per protocol primary efficacy population, the ORR was 50% (2 CR and 10 PR); 14 (58%) had progression free survival (PFS) ≥ 24 weeks and the median PFS has not yet been reached with a median follow-up of 8 mos. Eighty-three percent of pts experienced treatment emergent AEs (TEAEs), with the most common (≥ 10%) TEAEs regardless of relationship including diarrhea, pyrexia, fatigue, cough, decreased weight, vomiting, decreased appetite, nausea, anemia and headache. Fifty-five percent of pts presented with Grade 3/4 TEAES (any relationship) which included lymphopenia (13%) and the following TEAEs in less than 10% of pts: anemia, pneumonia, neutropenia, alanine aminotransferase elevation (ALT), diarrhea, hypokalemia, hyperglycemia, thrombocytopenia, decreased appetite and general physical health deterioration. Fifty-four percent of pts had serious adverse events but only the following events were reported as related to SAR245409: general physical health deterioration, diarrhea, hypophosphatemia, lung infection and cortical cataracts. The pre-specified criteria for the primary endpoint of ORR of at least 25% was achieved in Stage 1 and the FL arm has been expanded to enroll Stage 2. Conclusions Single agent SAR245409 exhibited clinical activity and an acceptable safety profile in patients with relapsed or refractory FL. Disclosures: Brown: Novartis: Consultancy; Avila: Consultancy; Vertex: Consultancy; Sanofi Aventis: Consultancy; Onyx: Consultancy; Emergent: Consultancy; Celgene: Consultancy, Research Funding; Genentech: Consultancy; Pharmacyclics: Consultancy; Genzyme: Research Funding. Off Label Use: The abstract shows scientific information on SAR245409 which is an investigational product developed by Sanofi. This investigational product is not approved by any health authority for any indication. Karlin:Celgene: Expert board Other, Honoraria; Janssen: Honoraria. Hayslip:Sanofi: Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Celgene: Research Funding. Wagner-Johnston:Celgene: Research Funding. Cartron:Roche: Consultancy, Honoraria, Speakers Bureau; GSK: Honoraria; LFB: Honoraria. Ribrag:Servier: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity’s Board of Directors or advisory committees; Bayer: Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; J&J: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Opat:Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Tilly:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Takeda: Membership on an entity’s Board of Directors or advisory committees; Pfizer: Honoraria; Janssen: Honoraria; Amgen: Research Funding. Janssens:Amgen: Speakers Bureau; Roche: Speakers Bureau; GSK: Speakers Bureau. Offner:Lilly: Membership on an entity’s Board of Directors or advisory committees. Ganguly:Sanofi: Research Funding. Millenson:Sanofi: My spouse was previously employed by Sanofi (within the past 24 months, ending April 2013) Other. Bron:Sanofi: Research Funding. Xu:Sanofi: Employment. Ruiz-Soto:Sanofi: Employment. Kersten:Sanofi: Honoraria, Member of steering committee for this study Other.

Description: Abstract 302 Background: Marizomib has a novel, non-peptide based, bicyclic structure and compared to other proteasome inhibitors, unique properties of clinical relevance. Specifically, marizomib produces rapid, broad and prolonged inhibition of all 3 20S proteasome catalytic activities, and markedly different safety and efficacy profiles, including activity against MM resistant to bortezomib (BZ) both in vitro and in vivo. Materials and Methods: Marizomib was given IV over 1–120 minutes on days 1, 4, 8 and 11 of 21-day cycles in 2 separate and parallel dose escalation studies performed in Australia and the United States in patients with relapsed and refractory MM. In addition to standard safety and efficacy monitoring, pharmacokinetics (PK) and proteasome inhibition as part of pharmacodynamics (PD) were assessed. Dexamethasone (20 mg) was given the day prior to and day of treatment in one study and could be added for patients who did not achieve a minimal response (MR) or better after 2 cycles in the other study. Toxicity evaluation was performed using CTCAE v3.0 and response was assessed by modified European Group for Blood and Marrow Transplantation (EBMT) and Uniform Criteria (UC). Results: 34 patients (16 men and 18 women) have been treated at doses of 0.075 to 0.6 mg/m2/dose BIW with a median age of 62.5 years, in both studies. Patients received a median of 6 prior regimens; 30 patients (88%) had been exposed to prior BZ, including 24 (71%) who were BZ -refractory. The maximum tolerated dose of marizomib was found to be 0.4 mg/m2 over a 60 minute infusion time and 0.5 mg/m2 over a 120 minute infusion. Dose limiting toxicities included transient hallucinations, cognitive changes and loss of balance, all of which proved reversible. The most common drug-related adverse events were fatigue, nausea, vomiting, dizziness, headache, diarrhea, constipation, insomnia, anorexia, and dyspnea, which proved manageable with supportive care and/or dose reduction. Importantly, marizomib did not appear to induce myelosuppression, peripheral neuropathy (PN) or thrombocytopenia. PK analysis demonstrated a rapid elimination half-life (〈 20 minutes) and large volume of distribution, with PD analyses of packed whole blood (PWB) and peripheral blood mononuclear cells (PBMC) confirming dose dependent proteasome inhibition. At interim analysis, of 22 patients with evaluable disease for best response to marizomib +/− dexamethasone, 3 had achieved partial response (PR) by EBMT/UC (14%). In the active dose range of 0.4–0.6 mg/m2, 15 pts were evaluable with PR in 3 pts (20%), all of whom were refractory to prior BZ. Median time on treatment was 1.5 months, with stable disease or better documented in 16 pts (73%). Conclusions: The safety profile of marizomib clearly differs from BZ, without significant treatment–emergent PN or myelosuppression described. Preliminary results suggest anti-myeloma activity, with responses seen in patients in whom BZ had previously failed, as well as interesting PK/PD characteristics and tissue distribution supporting a possible role in patients with different disease characteristics (such as extramedullary spread). The efficacy and safety of 0.5 mg/m2 of marizomib given twice weekly, alone or with low dose dexamethasone, warrants further study, and continues to be investigated. Future directions will include combination approaches with lenalidomide and dexamethasone. Disclosures: Richardson: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees. Cannell:Nereus Pharmaceuticals: Investigator. Harrison:Nereus Pharmaceuticals: Research Funding. Jakubowiak:Ortho Biotech: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Millennium Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Exelixis: Consultancy, Honoraria. Palladino:Nereus Pharmaceuticals, Inc: Employment, Equity Ownership. Longenecker:Nereus Pharmaceuticals, Inc: Employment, Equity Ownership. Lay:Nereus Pharmaceuticals, Inc: Employment, Equity Ownership. Lloyd:Nereus Pharmaceuticals, Inc: Employment, Equity Ownership. Hannah:Nereus Pharmaceuticals, Inc.: Consultancy. Reich:Nereus Pharmaceuticals: Consultancy. Spear:Nereus Pharmaceuticals, Inc: Employment, Equity Ownership. Anderson:Onyx: Consultancy; Merck: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acetylon: Founder; Nereus Pharmaceuticals, Inc: Consultancy; Millennium: Consultancy; Celgene: Consultancy.

Description: Background: Anthracylines are one of the major classes of drugs active against acute myeloid leukemia (AML). Increased doses of daunorubicin during induction therapy for AML have been shown to improve remission rates and survival. The ALLG used idarubicin in induction therapy at a dose of 9 mg/m2 x 3 days (total dose 27 mg/m2) in combination with high-dose cytarabine and etoposide (Blood 2005, 105:481), but showed that a total idarubicin dose of 36 mg/m2 was too toxic in this context (Leukemia 2001, 15:1331). In order to further improve outcomes in adult AML by anthracycline dose escalation, we conducted a phase 3 trial comparing standard to an increased idarubicin dose during consolidation therapy. Methods: Patients achieving complete remission after 1 or 2 cycles of intensive induction therapy (idarubicin 9 mg/m2 daily x3, cytarabine 3 g/m2 twice daily on days 1,3,5 and 7, and etoposide 75 mg/m2 daily x7; ICE protocol) were randomized to receive 2 cycles of consolidation therapy with cytarabine 100 mg/m2 per day for 5 days, etoposide 75 mg/m2 for 5 days, and idarubicin 9mg/m2 daily for either 2 or 3 days (standard and intensive arms respectively). No further protocol therapy was given. The primary endpoint was leukemia-free survival from randomization to consolidation therapy (LFS) with overall survival (OS) as secondary endpoint. Results: A total of 422 patients with AML (excluding cases with CBF rearrangements or APL) aged 16 to 60 years were enrolled between 2003-10, with 345 (82%) achieving complete remission, and 293 being randomized to standard (n=146) or intensive (n=147) consolidation arms. The median age was 45 years in both arms (range 16- 60), and both groups were balanced for intermediate versus unfavorable karyotypes and for frequency of mutations involving FLT3-ITD and NPM1 genes. Of the randomized patients, 120 in the standard arm (82%) and 95 in the intensive arm (65%) received the second consolidation cycle (p

Description: Background: In the phase 3 TOWER study, patients with relapsed or refractory (r/r) Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) who received bispecific T-cell engager (BiTE®) antibody construct blinatumomab had improved overall survival (OS; median, 7.7 vs 4.0 months; P=0.01;) and health-related quality of life (HRQoL) compared with those who received standard of care (SOC) chemotherapy (Kantarjian H, et al. N Engl J Med. 2017;376:836-847; Topp MS, et al. Blood. 2018;131:2906-2914). In this subgroup analysis of TOWER, we assessed the HRQoL between patients with low versus high baseline disease burden (low versus high bone marrow blast levels) who received blinatumomab or SOC chemotherapy. Methods: Patients (N=405) with r/r Ph- BCP ALL were randomized 2:1 to receive 2 cycles of induction blinatumomab by continuous intravenous infusion (n=271) or SOC (n=134). Those in remission could receive up to 3 consolidation cycles; 12 months of maintenance was allowed for those who received up to 3 consolidation cycles and had bone marrow response. HRQoL was assessed using the EORTC QLQ-C30 Questionnaire on days 1 (baseline), 8, and 15; on day 29 of cycle 1; days 1, 15, and 29 of consolidation; and at the safety follow-up. The questionnaire included 1 global health status scale, 5 functioning scales, 3 symptom scales, and 6 single-symptom items. For global health status and functioning scales, a higher score indicates better HRQoL; for symptom scales/items, a lower score indicates better HRQoL. A 10-point change was viewed as the minimum clinically important difference in EORTC QLQ-C30 (Zikos E, et al. EORTC. 2016). HRQoL was assessed in patient subgroups by screening the bone marrow aspirates for low blast levels (

Description: Abstract 3973 Aims: High-dose IV melphalan is standard autograft (ASCT) conditioning in patients with AL amyloidosis, but careful patient selection is required to avoid high transplant-related mortality rates. In patients ineligible for ASCT, intermediate-dose IV melphalan (IDM) may provide advantages over oral dosing where the already variable intestinal absorption is complicated by gastrointestinal amyloid deposition. We aimed to assess a risk-adapted strategy to IV melphalan dosing in patients with AL amyloidosis. Methods: The MM8 study was a prospective clinical trial conducted by the Australasian Leukaemia and Lymphoma Group. Transplant candidates (minimal cardiac disease including BNP