CLINICAL NEWS
On Location
American Society of Hematology’s
MEETING ON LYMPHOMA BIOLOGY
he 2016 ASH Meeting on Lymphoma Biology brought together experts from around
the world to discuss the latest breakthroughs in basic and translational lymphoma
research. Here, we present research highlights from the meeting, including ibrutinib in
high-risk chronic lymphocytic leukemia and the EZH2 inhibitor tazemetostat in previously treated non-Hodgkin lymphoma.
The meeting’s smaller format provided a forum for scientific exchange and fostered networking and collaboration among lymphoma researchers. The four-day event features didactic
sessions, abstract presentations, interactive workshops, and continuing conversations.
Ibrutinib Shows Survival Benefit in
Previously Treated CLL/SLL Patients
with High-Risk Disease
Longer-term data from the phase III RESONATE trial – a
head-to-head comparison of ibrutinib and ofatumumab –
continue to demonstrate ibrutinib’s efficacy in patients with
previously treated chronic lymphocytic leukemia (CLL), according to data presented at the 2016 ASH Meeting on Lymphoma Biology. The benefits also appear to extend to patients
with high-risk genetic mutations and poorer prognoses.
Historically, CLL with p53 dysfunction or del17p has
been difficult to treat, with few available therapeutic options,
according to Jennifer R. Brown, MD, PhD, director of the
CLL Center at Dana-Farber Cancer Center and associate
professor of medicine at Harvard Medical School, and first
author of the study.
With the advent of novel inhibitors, this may be changing. “These targeted therapies appear to be more effective
against CLL with p53 mutation and del17p, which is the
highest risk group [of patients],” Dr. Brown told ASH Clinical
News, “but there is still a question as to whether they completely reverse that adverse prognosis.”
To this end, Dr. Brown and her team examined two-
year progression-free survival (PFS), overall survival (OS),
and overall response rate (ORR) among patients with these
high-risk gene mutations enrolled in the RESONATE trial.
They also included patients who had NOTCH1, BIRC3, and
SF3B1 mutations – newly identified mutations also associated with worse survival in CLL.
RESONATE included 391 patients with relapsed or
refractory CLL or small lymphocytic leukemia (SLL) who
received at least one previous anti-cancer therapy. Patients
were randomized to receive oral ibrutinib 420 mg (n=142) or
intravenous ofatumumab (n=196) for up to 24 weeks.
REFERENCE
At 18-months of follow-up, 76 percent of ibrutinibBrown JR, Hillmen P, O’Brien S, et al. Efficacy of ibrutinib by baseline high-risk genetic features,
treated patients had not experienced disease progression,
including novel gene mutations, and safety with longer follow-up from the phase 3 RESONATETM
compared with eight percent in the ofatumumab-treated
trial in previously treated CLL/SLL. Abstract #88509. Presented at the 2016 ASH Meeting on
Lymphoma Biology, June 20, 2016; Colorado Springs, CO.
group. ORR was also higher with ibrutinib compared with
ofatumumab (90% vs. 25%; p value
not reported), regardless of baseline
genetic mutations (TABLE 1). AdTABLE 2. Progression-Free Survival and Overall Response
ditionally, patients who received one
Rate Among Patients with Novel Genetic Mutations
prior therapy fared significantly better
Progression-Free Survival and Overall Response
Rate by Subgroup
TABLE 1.
18-Month Progression-Free
Survival
Overall Response Rate
Ibrutinib
(n=142)
Ofatumumab
(n=149)
Ibrutinib
(n=142)
Ofatumumab
(n=149)
ATM
Mutated
77%
0
26/28 (93%)
8/33 (24%)
Unmutated
77%
8%
106/114 (93%)
32/116 (28%)
Mutated
77%
0
37/40 (93%)
13/45 (29%)
Unmutated
77%
11%
95/102 (93%)
27/104 (26%)
Mutated
65%
10%
42/43 (98%)
10/44 (23%)
Unmutated
83%
0
90/99 (91%)
30/105 (29%)
Mutated
73%
0
67/72 (93%)
13/68 (19%)
Unmutated
82%
9%
65/70 (93%)
27/81 (33%)
Ofatumumab
(n=196)
Ibrutinib
(n=195)
Ofatumumab
(n=196)
76%
8%
90%
25%
1
91%
11%
35/35 (100%)
14/53 (26%)
2
76%
0
≥3
71%
4%
Yes
83%
0
No
73%
10%
Prior therapy
141/160 (88%) 35/143 (24%)
Del11q
NOTCH1
SF3B1
TP53
57/63 (90%)
7/59 (12%)
114/127 (90%) 42/132 (32%)
Del17p
MYD88
Yes
71%
7%
56/63 (89%)
13/64 (20%)
Mutated
No
79%
8%
120/132 (91%)
36/132 (27%)
Unmutated
Unmutated
77%
0
90/98 (92%)
22/83 (27%)
Mutated
74%
15%
32/36 (89%)
12/49 (24%)
0
0
2/3 (67%)
1/3 (33%)
77%
8%
130/139 (93%)