Literature Scan
TABLE 2.
Best Overall Response to Midostaurin
Variable
Any subtype of advanced
symptomatic mastocytosis
(n=89)
Aggressive systemic
mastocytosis
(n=16)
Systemic mastocytosis
with an associated hematologic neoplasm
(n=57)
Mast-cell leukemia
(n=16)
Major or partial response as best overall response
Number of patients with response
53
12
33
8
60
(95% CI 49-70)
75
(95% CI 48-93)
58
(95% CI 44-71)
50
(95% CI 25-75)
24.1
(95% CI 10.8-not
evaluable)
Not reached
(95% CI 24.1-not
evaluable)
12.7
(95% CI 7.4-31.4)
Not reached
(95% CI 3.6-not
evaluable)
40 (45%)
10 (62%)
23 (40%)
7 (44%)
0
0
0
0
Incomplete remission
19 (21%)
6 (38%)
9 (16%)
4 (25%)
Pure clinical response
15 (17%)
4 (25%)
9 (16%)
2 (12%)
Overall response rate
Duration of response
Median number of months
Best overall response
Major response
Complete remission
Unspecified
6 (7%)
0
5 (9%)
1 (6%)
13 (15%)
2 (12%)
10 (18%)
1 (6%)
Good PR
11 (12%)
1 (6%)
10 (18%)
0
Minor PR
2 (2%)
1 (6%)
0
1 (6%)
Stable disease
11 (12%)
1 (6%)
7 (12%)
3 (19%)
Progressive disease
10 (11%)
1 (6%)
6 (11%)
3 (19%)
Not evaluable for response
15 (17%)
2 (12%)
11 (19%)
2 (12%)
Partial response (PR)
with respect to patient-reported symptoms
and quality of life,” the authors wrote, “that
may be related to combined inhibitory effects on the proliferation of neoplastic mast
cells and mediator release.”
“The clinical benefit of midostaurin in
patients with advanced SM represents a
large unmet therapeutic need,” Dr. Gotlib
concluded. “[The study] also validates the
principle that inhibition of KIT D816V, a
major driver of disease pathogenesis, is a
viable therapeutic strategy in SM.”
The study’s findings are limited by its
single-group design and lack of a comparator arm. The authors also noted that the
study was designed by the drug’s manufacturer – Novartis Pharmaceuticals – and a
steering committee. The sponsor collected
and analyzed the data in conjunctions with
the authors, who had full access to the data.
The authors noted that future studies are
needed to evaluate midostaurin in combination with other drugs and in the peri-transplant setting in patients with advanced SM.
REFERENCE
Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin
in advanced systemic mastocytosis. N Engl J Med. 2016;374:2530-41.
Post-Transplant Survival Rates Are Similar Between
Lymphoma Patients With Haploidentical Related
and HLA-Matched Sibling Donors
Allogeneic hematopoietic cell transplantation (alloHCT) is the only potentially
curative treatment option for patients
with high-risk relapsed or refractory lymphoma, but the lack of a human leukocyte
antigen (HLA)-matched sibling donor
(MSD) and delays in identifying matched
unrelated donors (URDs) remain challenges to using fully matched alloHCT.
In an analysis of data from the Center
for International Blood and Marrow
Transplant Research, investigators, led
by Nilanjan Ghosh, MD, PhD, from the
Levine Cancer Institute and the Carolinas
Healthcare System in Charlotte, North
Carolina, compared survival outcomes
between patients who received alloHCT
from haploidentical related donors
(haplo-HCT) or from MSD donors
(MSD-HCT).
The results of the observational
database study, published in the Journal
of Clinical Oncology, demonstrate that
overall survival (OS) rates were comparable regardless of donor source. Patients
undergoing haplo-HCT, however, had a
substantially lower risk of chronic graftversus-host disease (GVHD).
“This large analysis shows comparable
46
ASH Clinical News
outcomes between MSD transplantation
versus transplants from half-match ed related donors,” Mehdi Hamadani, MD, the
study’s corresponding author, told ASH
Clinical News. “Considering near universal availability of at least half-matched
family donors (parents, siblings, children,
etc.), donor unavailability should no
longer be considered a major barrier for
alloHCT.”
The researchers evaluated data from
987 patients with Hodgkin lymphoma
and non-Hodgkin lymphoma undergoing
their first reduced-intensity or non-myeloablative conditioning alloHCT between
2008 and 2013: 180 undergoing haploHCT and 807 undergoing MSD-HCT.
Haplo-HCT patients received GVHD
prophylaxis with post-transplant cyclophosphamide (PT-Cy) with or without a
calcineurin inhibitor and mycophenolate.
MSD-HCT patients received calcineurin
inhibitor-based prophylaxis. HaploHCT patients also received conditioning
with fludarabine and 200 cGy total body
irradiation (TBI); MSD-HCT patients received fludarabine plus an alkylator and/
or 200 cGy TBI.
Baseline characteristics were similar
for both cohorts, however, the haplo-HCT
group had a greater proportion of patients ≥60 years (35% vs. 24%; p<0.001),
African-American patients (15% vs. 4%;
p<0.001), and those with a Karnofsky
performance score ≥90 (79% vs. 68%;
p<0.001).
The median follow-up for surviving
patients was three years.
OS (the study’s primary endpoint) was
similar between both cohorts (61% [95%
CI 54-69] for haplo-HCT vs. 62% [95% CI
59-66] for MRD-HCT; p=0.82). Most patients achieved neutrophil recovery at 28
days: 95 percent in the haplo-HCT group
and 97 percent in the MSD-HCT group
(p=0.31). More patients in the MSD-HCT
group achieved platelet recovery at day 28
(91 percent vs. 63 percent; p<0.001), but
the numbers were similar at day 100 (96%
vs. 94%; p=0.33).
“The delay in platelet recovery in the
haplo-HCT cohort is likely due to the application of PT-Cy,” the authors wrote.
Both groups had a similar incidence
of grade 2-4 acute GVHD at day 100 (27%
for haplo-HCT patients vs. 25% for MSDHCT patients; p=0.84), while the cumulative incidence of chronic GVHD at one
year was significantly lower in haplo-HCT
patients (12% vs. 45%; p<0.001). Multivariate analysis confirmed the long-term
benefit of haplo-HCT for reducing the
risk of chronic GVHD (RR = 0.21; 95%
CI 0.14-0.31). See the TABLE for GVHD
outcomes.
At three-year follow-up, the cumulative incidence of disease progression and/
or relapse was 37 percent in the haploHCT cohort and 40 percent in the MSDHCT cohort (p=0.51). Rates of one-year
non-relapse mortality were also similar in
each cohort (10% for haplo-HCT vs. 9%
for MSD-HCT; p=0.57).
After a median follow-up of three
years, the progression-free survival (PFS)
was not significantly different between the
haplo-HCT and MSD-HCT groups (48%
for each; p=0.96).
The most common cause of death in
the haplo-HCT and MSD-HCT cohorts
was recurrent/progressive lymphoma
(47% [n=34] vs. 52% [n=151]). GVHD
was the cause of death in 13 patients in
the MSD cohort (5%) and one death in
the haploidentical cohort.
“These findings are paradigm shifting
in the sense that this is the first study – to
our knowledge – that shows outcomes
following an alternative donor source,
approaching those following matched
sibling transplantation, generally considered the best donor source for allogeneic
transplant,” Dr. Hamadani told ASH Clinical News. “[However], the results of our
study warrant confirmation in prospec-
September 2016