The American Society of Hematology (ASH) is the world’s largest professional society serving both clinicians and scientists working in the hematology field with over 17,000 members from almost 100 countries.
The ASH Annual Meeting & Exposition is the most comprehensive hematology event of the year, providing an educational experience and the opportunity to review thousands of scientific abstracts on the newest advancements and important topics in hematology. Attendees are able to network with a global community of over 25,000 hematology professionals.
At the 2018 ASH Annual Meeting & Exposition held in December, attendees were able to hear a presentation by National Cancer Institute (NCI) Director Norman E Sharpless, MD, who discussed his vision of big data, workforce development, and basic science at the NCI. Sessions were also held regarding new ASH guidelines and previews of guidelines to come in 2019.
Journal of Clinical Pathways and Oncology Learning Network were onsite at the meeting to cover the following presentations.
Outpatient Liposomal Daunorubicin and Cytarabine Induction in Patients With AML
A pilot outpatient program at the Memorial Healthcare System (Pembroke Pines, FL) demonstrated the safety and feasibility of liposomal daunorubicin and cytarabine induction and management in patients with secondary acute myeloid leukemia (AML).
Prior research has shown that liposomal daunorubicin and cytarabine (Vyxeos) improves overall survival and remission rates compared with conventional daunorubicin and cytarabine induction in older patients with secondary AML. Safety profiles are similar between these treatment strategies, and there is potential benefit of the liposomal combination—including the feasibility of outpatient administration—to improve patient satisfaction and health care costs.
Hugo F Fernandez, MD, department of malignant hematology and cellular therapy, Memorial Healthcare System, Moffitt Cancer Center (Pembroke Pines, FL), and colleagues designed a pilot program based on outpatient liposomal daunorubicin and cytarabine administration. Researchers hoped to compare the inpatient hospital days between patients with liposomal daunorubicin and cytarabine in the inpatient/outpatient (IPOP) program vs those in the inpatient setting.
The IPOP program involved administration of chemotherapy and close monitoring of patients in the outpatient setting who receive conventional inpatient chemotherapy regimens. Patients received liposomal induction at a dose of daunorubicin (44 mg/m2) and cytarabine (100 mg/m2) intravenous infusion over 90 minutes on days 1, 3, and 5.
Twelve patients were included in the program, of which 7 received IPOP induction and 5 received inpatient induction. Dr Fernandez and colleagues reported that 1 patient was admitted prior to completing the third induction dose, while the other 6 IPOP patients tolerated outpatient treatment well.
All IPOP patients were eventually admitted, with a median of 9 outpatient days prior to admission. Admissions were due to infectious complications. IPOP patients were hospitalized for 46% of the total days from start of induction until remission, progression, or recovery of neutrophils and platelets.
The mean cumulative days of inpatient and outpatient care were 19 and 22 days, respectively. Patients in the inpatient setting were hospitalized for 82% of their treatment course. Mean cumulative inpatient hospital days were significantly less in the IPOP group compared with the inpatient group (19 vs 31 days, respectively; P=.034).
Furthermore, researchers noted that the overall response rate among the entire patient population was 75% and was similar between the IPOP and inpatient groups. Overall safety profiles were similar between the 2 groups, they added.
“In this pilot program, IPOP liposomal daunorubicin and cytarabine induction and management appears to be safe and to significantly reduce the length of hospitalization in patients with secondary AML,” Dr Fernandez and colleagues concluded. “Future analyses with larger samples of patients are needed to further evaluate patient outcomes, safety and financial implications based on decreased inpatient hospital utilization.”
Superior PFS With Ibrutinib Alone or in Combination With Rituximab Compared With Bendamustine Plus Rituximab in Older Untreated Patients With CLL
In an international phase 3 trial, ibrutinib was shown to produce superior progression-free survival (PFS) compared with standard chemoimmunotherapy (CIT) in older patients with chronic lymphocytic leukemia (CLL).
There is no consensus yet on the most effective initial therapy for older adults with CLL due to the lack of comparison of CIT and targeted therapy with the Bruton tyrosine kinase inhibitor ibrutinib. Bendamustine plus rituximab (BR) is one standard, more aggressive CIT regimen for patients aged 65 or older. While ibrutinib has been approved by the Food and Drug Administration for untreated CLL since 2016, it has only been compared with chlorambucil and never before to aggressive CIT.
Jennifer A Woyach, MD, The Ohio State University Comprehensive Cancer Center, The Ohio State University (Columbus, OH), and colleagues were part of the Alliance A041202 study, a multicenter phase 3 study comparing BR (Arm 1) with ibrutinib (Arm 2) and the combination of ibrutinib plus rituximab (Arm 3) to determine whether ibrutinib-containing regimens are superior to CIT in terms of PFS. Researchers also investigated whether adding rituximab to ibrutinib would prolong PFS vs ibrutinib alone. At time of progression, patients on Arm 1 could cross over to Arm 2 (Clinical trials identifier: NCT01886872).
Participants were those aged ≥65 years with previously untreated, symptomatic CLL. Patients had a CrCl ≥40 mL/min, bilirubin ≤1.5 x ULN, and no significant life-limiting intercurrent illness or need for warfarin treatment. Patients were stratified based upon Rai stage, Zap-70 methylation performed centrally, and del(17)(p13.1) or del(11)(q22.3) by local interphase cytogenetics and were randomized 1:1:1 to each arm.
Between December 9, 2013, and May 16, 2016, 547 patients were registered and randomized (Arm 1: 183; Arm 2: 182; Arm 3: 182). Median age was 71 years and 67% of patients were men. Of those, 525 (96%) patients were eligible and included in the primary PFS analysis (Arms 1: 176, 2: 178, and 3: 171).
With median follow-up of 32 months, median PFS was 41 months in Arm 1 and has not been reached in Arms 2 or 3 (hazard ratio [HR] comparing Arm 2 to 1 is 0.40 with one-sided P<.0001; HR comparing Arm 3 to 1 is 0.41 with one-sided P<.0001; HR comparing Arm 3 to 2 is 1.01 with one-sided P=.48).
Two-year PFS estimates were 74%, 87%, and 88% in Arms 1, 2, and 3, respectively. There are no significant differences in overall survival (OS) at this time among arms (P=.87), median OS has not been reached for any arm, and 2-year OS estimates were 95%, 90%, and 94% in Arms 1, 2, and 3, respectively.
Adverse events (AEs) were compared among arms using Fisher’s exact tests. Grade 3+ treatment-emergent AEs were seen in 428 of 537 evaluable patients with 61%, 41%, and 38% of patients experiencing grade 3+ hematologic AEs (P<.0001) and 60%, 72%, and 71% of patients experiencing grade 3+ non-hematologic AEs (P=.03) in Arms 1, 2, and 3, respectively. Grade 5 AEs were seen in 5 (2.8%), 14 (7.8%), and 14 (7.7%) patients (P=.07).
Researchers concluded that ibrutinib produces superior PFS vs standard CIT in older patients with CLL, justifying this as a standard of care treatment for individuals aged 65 and older.
Authors noted that the addition of rituximab did not prolong PFS with ibrutinib, and, while ibrutinib represents a major therapeutic advance, toxicities and cost justify future efforts to reduce the need for long-term continuous treatment.