ASH Clinical News Advances in Hematology Research & Patient Care: Hi | Page 23

and vomiting.
Major hemorrhage occurred in 4 percent of the ibrutinib
population (grade 2 in 1 patient; grade 3 in 4 patients; and grade 4
in 1 patient), and in two percent of the chlorambucil population.
And, though hypertension was observed more frequently among
the ibrutinib cohort, it was limited to grade 1-3 and was managed
without modifying or discontinuing treatment.
AEs led to treatment discontinuation more frequently in the

chlorambucil group compared with the ibrutinib cohort (23% vs.
9%, respectively); at the time of the analysis, 87 percent of patients
receiving ibrutinib remained on therapy.
Reference
Tedeschi A, Barr PM, Robak T, et al. Results from the international, randomized
phase 3 study of ibrutinib versus chlorambucil in patients 65 years and older with
treatment-naïve CLL/SLL (RESONATE-2™). Abstract #495. Presented at the 2015
ASH Annual Meeting, December 7, 2015; Orlando, Florida.

Results from the Lumiere Trial: Shining a Light on Alisertib
in Relapsed/Refractory PTCL
Patients with relapsed and/or refractory peripheral T-cell
lymphoma (PTCL) have limited treatment options, and,
subsequently, poor survival outcomes. Alisertib, an investigational oral selective inhibitor of Aurora A kinase, may
have a place in treating PTCL but has not yet shown superiority over other agents, according to results from an interim
analysis of the Lumiere trial.

Alisertib has shown promising anti-tumor activity in previous phase
II studies of patients with relapsed and/or refractory PTCL, but this
is the first phase III trial to evaluate single-agent alisertib against
investigator’s choice in these patients. The results were presented
by Owen A. O’Connor, MD, PhD, from the Center for Lymphoid
Malignancies at the Columbia University Medical Center at the New
York Presbyterian Hospital.
238 patients from 27 countries were randomized 1:1 to receive:
• Alisertib: 50 mg twice daily on days 1-7 in 21-day cycles (n=120)
• Investigator’s choice (n=118), including:
°° Pralatrexate: 30 mg/m2 intravenously (IV) once weekly for 6
weeks in 7-week cycles
°° Romidepsin: 14 mg/m2 IV on days 1, 8, and 15 in 28-day cycles
°° Gemcitabine: 1,000 mg/m2 IV on days 1, 8, and 15 in 28-day cycles

ern Cooperative Oncology Group performance status of 0-2.
Patients received treatment for two years or until disease progression or unacceptable toxicity, though patients could continue
treatment past two years if a benefit was shown.
Patients taking alisertib were followed for a median of 9.5 months
while those in the comparator regimens were followed for a median
of 9.2 months. As seen in TABLE 7, ORR was lower among those taking
alisertib, for an odds ratio (OR) of 0.65 (95% CI 0.34-1.23). Median
overall survival (OS) was also shorter among patients receiving alisertib
compared with the investigator’s choice of treatment: 9.2 months and
12.2 months (hazard ratio [HR] = 0.901; 95% CI 0.607-1.337).
Median progression-free survival, though, was similar among
both groups: 3.7 months for the alisertib cohort versus 3.4 months
for the comparator cohort (HR=0.939; 95% CI 0.681-1.293).
Treatment duration was longer in patients receiving alisertib than
with the other cohorts (12 weeks vs. 10 weeks, respectively), with 15 percent and 5 percent of patients remaining on treatment after two years.
Grade 3 or higher adverse events occurring in the alisertib versus comparator cohorts included, respectively:
• Neutropenia (44% vs. 27%)
• Thrombocytopenia (29% vs. 27%)
• Anemia (30% vs. 11%, respectively)

All patients included in the study had previously taken one or more
conventional systemic cytotoxic therapies, had measurable disease
according to the 2007 International Working Group criteria, had a
tumor biopsy for central hematopathology review, and had an East-

“While alisertib showed activity in relapsed/refractory PTCL, there
was no significant efficacy benefit versus the comparators,” the authors concluded. Although final results are pending, “based on these
interim data, there was a low probability of
claiming superiority of alisertib for PFS at
TABLE 7. Comparison of Efficacy of Alisertib and Investigator’s Choice
the final analysis.”

Response

Alisertib 
(n=83)

ORR

Comparator

All
(n=80)

Pralatrexate
(n=40)

Romidepsin
(n=17)

Gemcitabine
(n=23)

27 (33%)

34 (43%)

16 (40%)

10 (59%)

8 (35%)

Complete response

13 (16%)

20 (25%)

10 (25%)

5 (29%)

5 (22%)

Partial response

14 (17%)

14 (18%)

6 (15%)

5 (29%)

3 (13%)

Stable disease

26 (31%)

18 (23%)

13 (33%)

2 (12%)

3 (13%)

Progressive disease

30 (36%)

27 (34%)

11 (28%)

4 (24%)

12 (52%)

Reference
O’Connor OA, Ozcan M, Jacobsen ED, et al. First
multicenter, randomized phase 3 study in patients
(pts) with relapsed refractory (R/R) peripheral
T-cell lymphoma (PTCL): alisertib (MLN8237) versus
investigators choice (Lumiere trial; NCT01482962).
Abstract #341. Presented at the 2015 ASH Annual
Meeting, December 6, 2015; Orlando, Florida.

ORR=objective response rate
January 2016

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