ASH Clinical News ACN_4.4_SUPP_Digital Version | Page 15

CC-122 Plus Obinutuzumab: An Effective, Chemotherapy-
Free Regimen for Non-Hodgkin Lymphoma?
Results from a phase Ib study of CC-122 (an oral agent that
binds the cereblon ubiquitin ligase complex), in combina-
tion with obinutuzumab, showed positive response rates
in patients with relapsed and refractory B-cell non-Hodgkin
lymphoma (NHL), according to a presentation at the 2017
ASH Annual Meeting. At 12-month follow-up, two-thirds of
patients responded to this chemotherapy-free regimen with-
out new safety signals.
“Patients with relapsed/refractory NHL, including follicular
lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)
have a poor prognosis with limited second- and thirdline treat-
ment options,” noted lead author Jean-Marie Michot, MD, of
Institut Gustave Roussy in Villejuif, France. “[Patients with FL]
experiencing progression within two years of initial diagnosis,
and those double-refractory to both rituximab and chemothera-
py have particularly poor outcomes,” the researchers noted.
The study enrolled 38 adult patients (median age = 60 years;
range = 26-81 years) who had histologically or cytologically
confirmed CD20-positive B-cell NHL that relapsed or was
refractory to one or more prior treatments for FL/marginal zone
lymphoma (MZL), or after two or more regimens and/or autol-
ogous hematopoietic cell transplantation (AHCT) for DLBCL.
The median number of prior therapies was four (range = 1-12
therapies); 14 patients (37%) had undergone AHCT.
Of the 38 participants, 19 had DLBCL, 18 had FL, and one had
MZL. In the FL cohort, 10 people were either double-refractory or
relapsed early and were considered “high risk,” the authors noted.
Eight patients (42%) with DLBCL had transformed DLBCL, and
eight (42%) with FL/MZL had disease that relapsed within 12
months of firstline treatment.
During 28-day cycles, patients received:
• CC-122 administered orally on days 1-5, followed by 2 days
off treatment in escalating doses (1, 2, 3, or 4 mg)
CC-122,” the researchers reported.
The 12-month overall response rate (ORR) was 66 percent,
with 11 patients (29%) achieving a complete response (CR).
When reviewing data across the subgroups, ORR and CR
rates were comparable regardless of disease type:
• DLBCL: 47% and 11%
• FL: 83% and 50%
Rates of 12-month progression-free survival (PFS; a secondary
efficacy endpoint) appeared to be higher among patients who
were double-refractory to rituximab and chemotherapy, compared
with those who were not (60% and 51%, respectively; p value not
provided). However, PFS rates were higher among patients who
had not experienced early relapse, compared with those who did
(58% and 51%, respectively; p value not provided).
Overall, the authors concluded that the “chemotherapy-free
combination of CC-122 and obinutuzumab was well tolerated
with promising response rates, and durable remissions in relapsed/
refractory B-cell NHL.”
The small patient population and lack of a comparator arm
limit the findings of this early-phase study.
The authors report financial relationships with Celgene
(the manufacturer of CC-122) and Roche (the manufacturer of
obinutuzumab).
REFERENCE
Michot J, Bouabdallah R, Doorduijn JK, et al. CC-122, a novel cereblon modulating
agent, in combination with obinutuzumab (GA101) in patients with relapsed and
refractory (R/R) B–cell non–Hodgkin lymphoma (NHL). Abstract #411. Presented
at the 2017 American Society of Hematology Annual Meeting, December 10, 2017;
Atlanta, GA.
SCENES FROM THE 2017 ASH ANNUAL MEETING
• intravenous obinutuzumab 1,000 mg on days 2, 8, and 15 of
cycle 1, and day 1 of cycles 2-8
As of May 1, 2017 (data cutoff), patients were followed for at
least 12 months.
Two patients experienced a dose-limiting toxicity: one grade
4 neutropenia (at CC-122 3 mg) and one grade 5 tumor flare (at
CC-122 4 mg). The most common (occurring in ≥10% of patients)
grade 3/4 treatment-related adverse events (AEs) included neutro-
penia (55%) and thrombocytopenia (26%). Eight patients (21%)
experienced at least one serious AE related to CC-122, but febrile
neutropenia (n=2) was the only serious AE to occur in at least two
patients. Three deaths occurred: two related to progressive disease
and one related to an AE (tumor flare). “The safety profile [the
study’s primary endpoint] was consistent with other studies of
March 2018
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