MEETING NEWS
Highlights from the 2019 ASH Annual Meeting
synergize to reduce growth of ALL xenografts; in addi-
tion, combining venetoclax and navitoclax may mitigate
dose-limiting toxicities previously observed with standard-
dose navitoclax monotherapy.”
In this phase I, multicenter, open-label, dose-escalation
study, investigators evaluated a weight-adjusted regimen
of venetoclax plus navitoclax in patients with B-cell ALL,
T-cell ALL, or lymphocytic lymphoma (LL). Patients were
excluded if they had received chimeric antigen receptor
(CAR) T-cell therapy, a biologic agent, or inotuzumab with-
in 30 days or any other anti-cancer therapy within 14 days.
As of the data presentation, 45 patients with B-cell
ALL (n=24), T-cell ALL (n=18), or LL (n=3) were enrolled
in the trial. The median age was 29 years (range = 6-72)
and the median number of prior therapies was 4 (range =
1-10). “Many patients had [disease that] failed prior cellu-
lar therapies or immunotherapies,” Dr. Lacayo noted. “Of
patients with B-cell ALL, 50% had prior blinatumomab,
29% had prior inotuzumab, and 29% had prior CAR T-cell
therapy.” Approximately one-third had prior hematopoi-
etic cell transplantation.
Per study protocol, patients received an initial ramp-up
dose of venetoclax 200 mg (or weight-adjusted equivalent)
on day 1, and 400 mg thereafter. Navitoclax was added at day
3, at doses of 25, 50, or 100 mg for patients weighing ≥45 kg
or at doses of 25 or 50 mg for patients weighing 20 to <45 kg.
Participants also received 2 cycles of backbone chemother-
apy (asparaginase, vincristine, and dexamethasone), with
additional cycles allowed at the investigators’ discretion.
The median time on study was 8 months (range =
6-12). Nearly all patients (98%) experienced an any-grade
treatment-emergent AE, and many experienced a grade
3/4 AE (93%). The most common grade 3/4 AEs included:
• febrile neutropenia (40%)
• hypokalemia (22%)
• neutropenia (22%)
• anemia (18%)
Dr. Lacayo pointed out that 58% of patients had grade
3/4 AEs related to venetoclax and 42% had grade 3/4 AEs
related to navitoclax.
During the study, 4 patients (9%) discontinued treat-
ment due to AEs, and 1 patient died due to a treatment-
related AE (intestinal ischemia). Seven patients (16%)
experienced a dose-limiting toxicity (the study’s primary
endpoint), including 4 cases of delayed count recovery, 1
case of drug-induced liver injury; 1 case of intestinal isch-
emia; and 1 case of increased blood bilirubin.
In terms of efficacy, preliminary results show that, of the
45 patients enrolled, 22 (49%) experienced a CR, CR with
incomplete marrow recovery (CRi), or a CR with incomplete
24
Focus on Lymphoid & Plasma Cell Malignancies
platelet recovery (CRp). Another 4 patients (9%) had a par-
tial response, for an overall response rate of 58%. Responses
occurred within a median of 1.2 months (range = 0.2-3.5),
and the median duration of response was 9.1 months (range
= 1.9-11.5). In addition, 11 patients were able to proceed to
CAR T-cell therapy or hematopoietic cell transplantation.
Dr. Lacayo noted that 12 responders were considered
measurable residual disease (MRD)–negative, also high-
lighting that, of 11 pediatric patients enrolled, 6 (55%)
had a CR/CRi/CRp and 5 achieved MRD negativity.
The findings of this early-phase study are limited by
the small patient population, as well as the open-label
and non-randomized design. An expansion cohort is
enrolling patients to explore a 21-day dosing schedule of
venetoclax plus navitoclax 50 mg to mitigate prolonged
count recovery, which was a dose-limiting toxicity report-
ed in the present study, Dr. Lacayo concluded.
Study authors report relationships with AbbVie, which
sponsored the trial.
Reference
Lacayo NJ, Pullarkat VA, Stock W, et al. Safety and efficacy of venetoclax in combination with navi-
toclax in adult and pediatric relapsed/refractory acute lymphoblastic leukemia and lymphoblastic
lymphoma. Abstract #285. Presented at the 2019 ASH Annual Meeting, December 8, 2019; Orlando, FL.
DDGP Versus SMILE:
Comparing Regimens for
Extranodal Natural Killer
T-Cell Lymphoma
In patients with extranodal natural killer T-cell lymphoma (ENKTL),
treatment with the chemotherapy regimen of dexamethasone,
cisplatin, gemcitabine, and pegasparaginase (DDGP) improved
survival compared with those treated with dexamethasone,
methotrexate, ifosfamide, asparaginase, and etoposide (SMILE),
according to a study presented by Mingzhi Zhang, MD, PhD, from
the First Affiliated Hospital of Zhengzhou University in China, at the
2019 ASH Annual Meeting. DDGP-treated patients also had lower
rates of grade 3/4 adverse events.
“A subtype of highly aggressive mature T/NK-cell lym-
phomas, [ENKTL] is characterized by Epstein-Barr virus
infection and varying degrees of systemic inflammation,”
Dr. Zhang explained. While it is rare in Western coun-
tries, it is rather common in Asia, with a higher incidence
among men than women. “Patients with advanced stage
III or IV ENKTL have a poor survival and low response
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