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Background Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. MethodsIn this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0-2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. Findings Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60-72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61-72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6•8 months (95% CI 5•0-8•5; 165 [67%] of 246 patients had an event) in the melflufen group and 4•9 months (4•2-5•7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0•79, [95% CI 0•64-0•98]; p=0•032), at a median follow-up of 15•5 months (IQR 9•4-22•8) in the melflufen group and 16•3 months (10•1-23•2) in the pomalidomide group. Median overall survival was 19•8 months (95% CI 15•1-25•6) at a median follow-up of 19•8 months (IQR 12•0-25•0) in the melflufen group and 25•0 months (95% CI 18•1-31•9) in the pomalidomide group at a median follow-up of 18•6 months (IQR 11•8-23•7; HR 1•10 [95% CI 0•85-1•44]; p=0•47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs...

Background: Gilteritinib, a highly selective, potent FLT3/AXL inhibitor, showed antileukemic activity with favorable tolerability in a phase 1/2 trial of patients (pts) with FLT3mut+ relapsed/refractory AML (Perl AE, et al. Lancet Oncol. 2017). Gilteritinib plus azacitidine (AZA) synergistically induced apoptosis and inhibited growth in the MV4-11 cell line and in MV4-11 tumors (Ueno Y, et al. Blood. 2016). The safety, tolerability, and efficacy of gilteritinib alone, gilteritinib plus AZA, or AZA alone is being evaluated in pts with newly diagnosed FLT3mut+ AML ineligible for intensive induction chemotherapy; this abstract presents data from the Safety Cohort which evaluated only gilteritinib plus AZA. Methods: Adults with newly diagnosed FLT3mut+ (FLT3-ITD or FLT3-TKD) AML are being enrolled in this ongoing clinical trial (NCT02752035). Prior to initiation of the randomized portion of the study, the appropriate gilteritinib dose for combination therapy was assessed in a Safety Cohort. Patients enrolled in this cohort received escalating doses of oral gilteritinib (80 or 120 mg/day) on Days 1-28 in combination with subcutaneous or intravenous AZA (75 mg/m2/day) on Days 1-7. Observations of dose-limiting toxicities (DLTs) were collected through Cycle 1; treatment was continued in 28-day cycles until lack of clinical benefit or unacceptable toxicity. Safety and tolerability were the primary endpoints of the Safety Cohort; antileukemic response rates (ie, complete remission [CR], CR with incomplete platelet recovery [CRp], CR with incomplete hematological recovery [CRi], partial remission [PR], and overall response rate [ORR]) were also assessed. Results: A total of 15 adult pts (median age, 76 [range: 65-86]) were enrolled into the Safety Cohort (n=9, 80 mg gilteritinib; n=6, 120 mg gilteritinib); 14 pts were FLT3mut+ (ITD alone, n=10; TKD alone, n=3; ITD and TKD, n=1) and 1 pt had no FLT3 mutation. As of 25 June 2018, more than half (n=8/15; 56%, Figure) of the pts had a treatment duration of >6 mo, while 9 pts discontinued treatment (death, n=4; relapse; adverse event [AE]; physician decision; sponsor decision; subject withdrawal, n=1 each) and 6 pts remained on treatment. During the DLT observation period, 1 DLT (tumor lysis syndrome) was observed in a pt who received 80 mg gilteritinib plus AZA; no DLTs were reported in pts who received 120 mg gilteritinib plus AZA. One or more AEs were seen in all 15 pts; 12 (80%) experienced AEs considered at least possibly related to treatment. Adverse events occurring in ≥25% of pts were anemia (n=7), febrile neutropenia and nausea (n=6 each), increased ALT and AST, constipation, diarrhea, neutropenia, thrombocytopenia, and pyrexia (n=5 each), and decreased appetite, fatigue, increased blood creatinine, and hypocalcemia (n=4 each). Grade ≥3 AEs occurring in ≥25% of pts were febrile neutropenia (n=6), anemia and neutropenia (n=5 each), and thrombocytopenia (n=4). Serious AEs occurring in >2 pts were febrile neutropenia (n=5), and anemia and pyrexia (n=3 each). Of the 8 pts with fatal AEs, none of which were related to treatment, 3 occurred early in treatment: septic shock (Day 2), respiratory failure (Day 6), and cerebral hemorrhage in the setting of acute kidney injury and uremia (Day 17). None of the 13 pts with post-baseline lab data had any potentially clinically significant AST/ALT (>3 X ULN) and total bilirubin (>2 X ULN) values; none of the pts had a maximum post-baseline QTcF interval >500 msec. Across the Safety Cohort, a composite complete remission rate of 67% (n=10/15) was observed; 4 pts achieved a best overall response of CR and 6 achieved CRi (Figure). Two additional pts (13%) achieved a best overall response of PR, giving an ORR of 80%. One DLT from the 11 DLT evaluable pts (defined as pts who experienced a DLT, or in the absence of DLT, received at least 23 of 28 doses of gilteritinib and at least 5 of 7 doses of AZA during the DLT observation period) informed the decision to proceed to the randomized portion at a dose of 120 mg gilteritinib for the combination treatment arm. Conclusions: Gilteritinib and AZA were generally well tolerated with no unexpected AEs. This combination therapy induced antileukemic responses in newly diagnosed FLT3mut+ AML pts unfit to receive standard induction chemotherapy. Based on these results, pts are being enrolled into the randomized portion of the study with a dose of 120 mg gilteritinib for the combination treatment arm. Disclosures Wang: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Jazz: Speakers Bureau; Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy. Laribi:Amgen: Other: Personal fees; Takeda: Other: Grant and personal fees; Sandoz: Other: Grant; Novartis: Other: Grant and personal fees; Teva: Other: Grant; Gilead: Other: Personal fees; Hospira: Other: Grant; Roche: Other: Grant. Montesinos:Daiichi Sankyo: Consultancy, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Liu:Astellas Pharma: Employment. Rich:Astellas Pharma: Employment. Bahceci:Astellas Pharma: Employment.

Background/Aim: To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials. Patients and Methods: Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish 4059

18-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the most valuable imaging technique in Hodgkin lymphoma. Since its first use in lymphomas in the 1990s, it has become the gold standard in the staging and end-of-treatment remission assessment in patients with Hodgkin lymphoma. The possibility of using early (interim) PET during first-line therapy to evaluate chemosensitivity and thus personalize treatment at this stage holds great promise, and much attention is now being directed toward this goal. With high probability, it is believed that in the near future, the result of interim PET-CT would serve as a compass to optimize treatment. Also the role of PET in pre-transplant assessment is currently evolving. Much controversy surrounds the possibility of detecting relapse after completed treatment with the use of PET in surveillance in the absence of symptoms suggestive of recurrence and the results of published studies are rather discouraging because of low positive predictive value. This review presents current knowledge about the role of 18-FDG-PET/CT imaging at each point of management of patients with Hodgkin lymphoma.