CLINICAL NEWS
Literature Scan
the last plasma exchange, with a maximum treatment
duration of 90 days.
The median time to response (defined as confirmed
normalization of the platelet count) was three days for the
caplacizumab cohort (95% CI 2.7-3.9) compared with 4.9
days for the placebo group (95% CI 3.2-6.6) – a 39 percent
reduction (95% CI 1.28-3.78; p=0.005).
At one-month of follow-up, complete remission (defined as normalization of the platelet count and an absence
of exacerbations after the initial course of daily plasma exchange) was observed more frequently with caplacizumab
than placebo (81% vs. 46%; p value not available).
Three of the caplacizumab-treated patients had exacerbations of disease activity (defined as recurrent thrombocytopenia within 30 days after the end of daily plasma
exchanges that required re-initiation of daily exchanges),
compared with 11 of the placebo-treated patients. “The
number of days of plasma exchange also was reduced,” Dr.
Callewaert added. “This means that the patient is discharged from the hospital sooner and is less dependent on
plasma exchange with its associated complications.”
Following cessation of the study drug, eight patients
who had received caplacizumab relapsed – sev en of them
within 10 days of cessation – while no patients in the placebo cohort relapsed.
“This between-group difference suggests that, among
patients who were destined to have an exacerbation, it
occurred during study-drug administration in the placebo
group, whereas caplacizumab may have delayed the exacerbation until after the period of study-drug administration,”
the authors observed.
The majority of patients who experienced disease exacerbation or had a relapse early after cessation of the study
drug also had continuing low ADAMTS13 levels (<10%),
indicating unresolved autoimmune activity and suggesting
that ADAMTS13 activity could be used to predict patients
at risk for relapse and could guide decisions about the
duration of caplacizumab treatment, in addition to guiding
immunosuppressive treatment.
Adverse events (AEs) occurred in 97 percent of caplacizumab-treated patients (n=34/35) and all placebo-treated
patients (n=37), the most common of which were headache
and epistaxis. Most of the reported AEs were considered
unrelated to study treatment. Two deaths occurred during
the study, both of which were in the placebo group.
Caplacizumab-treated patients were more likely to have
bleeding-related AEs, compared with the placebo cohort
(54% vs. 38%; p value not available). Serious bleedingrelated AEs were reported in two patients in each study
group: subarachnoid and retinal hemorrhage and metrorrhagia in the caplacizumab group and cerebral hemorrhage
and hematuria in the placebo group.
Similarly, immune-related AEs were reported more
often in the caplacizumab than in the placebo group (49%
vs. 32%; p value not available).
“On the basis of its pharmacologic effect, we expected
that caplacizumab treatment would be associated with an
increased risk of bleeding,” the authors explained. “Although bleeding events were observed more frequently in
the caplacizumab group than in the placebo group, these
events were generally mild and did not require treatment.”
Ultimately, Dr. Peyvandi and co-authors concluded,
“caplacizumab prevents further platelet aggregation more
rapidly than conventional treatment alone, which could
potentially prevent short- and long-term end-organ injury
due to ischemia.” They noted, however, the limitation that
this observation may have been confounded by the diluting effect of plasma exchange.
REFERENCE
Peyvandi F, Scully M, Hovinga JAK, et al. Caplacizumab for acquired thrombotic thrombocytopenic
purpura. N Engl J Med. 2016;374:511-22.
50
ASH Clinical News
Examining a PET-Response–
Adapted Strategy in Patients with
Advanced Hodgkin Lymphoma
Positron emission tomography (PET) performed
early during first-line therapy in patients with
advanced-stage Hodgkin lymphoma (HL)
can identify patients who would benefit from
therapy escalation, according to a report recently
published in the Journal of Clinical Oncology.
In the phase II HD0801 study, Pier Luigi
Zinzani, MD, from the Sant’Orsola-Malpighi
University Hospital in Italy, and colleagues examined whether poor response to ABVD chemotherapy (determined by PET-positivity) could
provide a rationale to shift patients to a more
intensive treatment regimen.
“This strategy is opposed to the conventional approach of addressing patients to
salvage treatment only after a disease relapse
or resistance is demonstrated,” Dr. Zinzani told
ASH Clinical News.
“Our data support the
efficacy and feasibility
of early treatment
intensification in a
small proportion
of patients with
Hodgkin lymphoma
considered at high
risk for failure.”
—PIER LUIGI ZINZANI, MD
The multicenter study assessed two-year
progression-free survival (PFS; the primary
endpoint) and overall survival (OS; the secondary
endpoint) among 519 patients with advancedstage de novo HL who received initial treatment
with doxorubicin, bleomycin, vinblastine, and
dacarbazine (ABVD).
If patients had a PET-positive evaluation
after two cycles of chemotherapy (PET2-positive), they underwent an ifosfamide-containing
salvage treatment followed by hematopoietic
cell transplantation (HCT). If patients were
PET-negative, they received four or more additional cycles of ABVD.
Within the study population, 103 evaluable
patients (20%) were PET2-positive, meaning
treatment was at high risk for failing. Of those
patients:
• 81 received the scheduled salvage regimen
with HCT
• 15 remained on ABVD therapy
• 5 received an alternative treatment
• 2 were excluded from the study due to
diagnostic error
Twenty-one patients in the PET2-positive
group and 73 in the PET2-negative group
experienced disease progression. Eight patients
in the PET2-positive group and nine patients in
the PET2-negative group died during the study
follow-up period.
Among the 81 patients who received salvage
treatment, grade 3 and 4 adverse events were
primarily hematologic and treatment-related,
including neutropenia (11% and 60%) and
thrombocytopenia (15% and 49%). No treatment toxicity-related hospitalizations or deaths
occurred, “thus achieving a favorable toxicity
profile for such an intensive therapeutic strategy,” the authors wrote.
In an intention-to-treat analysis, rates
of two-year PFS after a median follow-up of
25 months from PET scanning were similar
between PET2-negative and PET2-positive patients (regardless of the salvage treatment they
received): 81 percent (95% CI 76-84) and 76
percent (95% CI 66-84), respectively. “[These
patients] appear to benefit from early treatment
intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70 percent
of PET2-positive patients through obtaining
the same two-year PFS as the PET2-negative
subgroup,” the authors concluded.
“Our data support the efficacy and feasibility of early treatment intensification in a small
proportion of patients with Hodgkin lymphoma
considered at high risk for failure, as identified
by an interim PET2 positivity,” Dr. Zinzani told
ASH Clinical News.
The authors noted one result limiting the
study’s findings: A group of 15 PET2-positive
patients received fou r or more cycles of ABVD
as a result of the physician’s or patient’s refusal to
switch to the treatment program, and 73 percent
achieved a complete response, “indicating the existence of a proportion of patients who can obtain
a complete response even though they show PET
positivity at early evaluation.”
Given this finding, there is a risk of overtreatment of PET2-positive patients, and longer
follow-up is necessary to confirm the validity of
this PET response-adapted strategy in advanced
HL patients. ●
REFERENCE
Zinzani PL, Broccoli A, Gioia DM, et al. Interim positron emission tomography
response—adapted therapy in advanced-stage Hodgkin lymphoma: Final results of the
phase II part of the HD0801 study. J Clin Oncol. 2016 Feb 16. [Epub ahead of print]
April 2016