MEETING NEWS
Highlights from the 2019 ASH Annual Meeting
Continued from page 24
to conventional CHOP [cyclophosphamide, doxorubicin,
vincristine, prednisone]–like chemotherapy, with a 5-year
overall survival rate of 30 to 50%.” In earlier research, the
SMILE chemotherapy regimen was efficacious in ENKTL,
but its toxicity profile limited its clinical use.
In this prospective, randomized, multicenter, open-label
trial, Dr. Zhang and researchers evaluated the safety and
efficacy of the DDGP regimen, compared with SMILE, in
patients with newly diagnosed stage III/IV ENKTL.
The study included 87 patients treated at one of nine
centers in China between January 2011 and February 2019.
Participants were between the ages of 14 and 70 and had
an Eastern Cooperative Oncology Group ECOG perfor-
mance status of 0 to 2.
Patients were randomized to receive DDGP or SMILE in
the following schedules, for up to six 21-day cycles or until
disease progression, unacceptable toxicity, or patient refusal:
• DDGP: cisplatin 20 mg/m 2 on days 1-4, dexamethasone
15 mg/m 2 on days 1-5, gemcitabine 800 mg/m 2 on days 1
and 8, and pegasparaginase 2,500 IU/m 2 on day 1
• SMILE: methotrexate 2 g/m 2 on day 1, dexamethasone 40
mg/m 2 on days 2-4, ifosfamide 1,500 mg/m 2 on days 2-4,
L-asparaginase 6,000 U/m 2 on days 3-9, and etoposide
100 mg/m 2 on days 2-4
Dr. Zhang presented safety and efficacy results for 80
patients who were included in the intention-to-treat
population, 40 in the DDGP group and 40 in the SMILE
group. After a median follow-up of 41.5 months (range
not provided), the median progression-free survival (PFS;
primary endpoint) and overall survival (OS; co-secondary
endpoint) for patients treated with SMILE was 6.8 months
and 75.2 months, respectively. In the DDGP-treated
group, median PFS and OS were not reached (p=0.0041 for
PFS; p=0.02 for OS).
This also translated to higher 3-year PFS rates and 5-year
OS rates in the DDGP group:
• 3-year PFS: 57% with DDGP vs. 42% with SMILE (p=0.004)
• 5-year OS: 74% vs. 52% (p=0.02)
While there were no differences in the complete response
rates between the two arms (68% vs. 48%; p=0.011), the
overall response rate (co-secondary endpoint) was signifi-
cantly higher in the DDGP group (90% vs. 60%; p=0.002).
As the researchers hypothesized, treatment with DDGP
was associated with less toxicity. Patients in the SMILE
cohort experienced more frequent grade 3/4 hematolog-
ic adverse events (AEs), including leukopenia (34 vs. 25;
p=0.022) and neutropenia (34 vs. 26; p=0.015), as well as
non-hematologic AEs, including elevated transaminase
(5 vs. 0; p=0.027), mucositis (3 vs. 0; p<0.001), and allergic
reaction (3 vs. 0; p=0.024).
Notably, there were more treatment-related deaths in the
SMILE group (18%) compared with the DDGP group (10%).
In the SMILE cohort, deaths were mainly related to infection
and hemorrhage due to bone marrow suppression.
Together, the results suggest that DDGP prolonged sur-
vival and reduced toxicity; however, the results are limited
by the relatively small patient population.
The study authors report no relevant conflicts of interests.
Reference
Wang X, Zhang L, Liu X, et al. Efficacy and survival in newly diagnosed advanced extranodal natural
killer/T-cell lymphoma: a randomized, controlled, multicenter and open-labeled study with DDGP
regimen versus SMILE regimen. Abstract #463. Presented at the 2019 American Society of
Hematology Annual Meeting, December 8, 2019; Orlando, FL.
Daratumumab-Based Induction and Response-Adapted
Consolidation Induces MRD Negativity in Patients With Newly
Diagnosed Myeloma
Induction therapy with daratumumab, carfilzomib, lenalidomide,
and dexamethasone (Dara-KRd) followed by autologous transplant
and Dara-KRd consolidation guided by measurable residual disease
(MRD) leads to high response rates in patients with newly-diagnosed
multiple myeloma (MM), according to preliminary results from the
MASTER trial presented at the 2019 ASH Annual Meeting.
When combined with a proteasome inhibitor or immu-
nomodulatory agent, the CD38-targeting antibody daratu-
mumab has been shown to increase the duration and depth
28
Focus on Lymphoid & Plasma Cell Malignancies
of response in patients with MM, explained lead author and
presenter Luciano J. Costa, MD, PhD, from the University
of Alabama at Birmingham. Carfilzomib has shown to be su-
perior to bortezomib in relapsed/refractory MM, and, when
combined with Rd, leads to high rates of very good partial
response (VGPR) or better in newly diagnosed patients.
“While responses are heterogeneous, treatment combina-
tions have traditionally been developed with a fixed number
of cycles, not accounting for kinetics or depth of response,”
Dr. Costa told ASH Clinical News.