Written in Blood
TMTV was associated with:
• extension of disease
• significantly bulkier
mediastinum
• more nodal involved areas
“If these data are confirmed,
[they] may help to design new
response-adapted therapeutic
strategies.”
—ANNE SÉGOLÈNE COTTEREAU, MD
• stage II disease
• B symptoms
• higher ESR
High TMTV was also associated
with significantly worse outcomes,
including:
• shorter PFS (hazard ratio [HR]
= 5.2; p<0.0001)
• shorter OS (HR=7.2; p=0.0001)
• lower rates of 5-year PFS (71%
vs. 92%; p<0.0001)
• lower rates of 5-year OS (83% vs.
98%; p<0.0001)
“The prognostic value of TMTV was
not impacted by the stratification on
the treatment arm,” the researchers
wrote. In a sub-analysis of patients with
unfavorable disease, TMTV maintained
prognostic significance for both PFS
(HR=4.2; p=0.0001) and OS (HR=4.0;
p=0.0035). Also, patients with low-
volume TMTV (74%) – despite having
unfavorable disease – had a five-year
PFS of 90 percent and OS of 96 percent,
compared with 67 percent and 80
percent, respectively, for patients with
TABLE 1.
high-volume TMTV.
The investigators then compared
the prognostic value of TMTV with
other baseline clinical and biologic
factors, including those used in the
EORTC, German Hodgkin Study
Group, and National Comprehensive
Cancer Network staging systems.
Multivariate analysis revealed that,
of all these factors, only TMTV and
iPET2 retained statistical significance
for both PFS and OS (see TABLE 1 ).
“Most of the parameters included
in the risk-assessment systems cur-
rently available for stratifying early-
stage HL are variably correlated to
disease extent, number, [and] size of
the area involved,” the authors wrote.
“Indeed, they are indirect and inac-
curate surrogates for tumor burden.”
The frequency of iPET2 positivity was
significantly higher in patients with
high TMTV, the authors reported,
suggesting that “PET/computed to-
mography could be more appropriate
to estimate tumor burden.”
In patients with a positive iPET2
(n=21), high TMTV was associated
with an HR for PFS of 3.4 (p=0.026)
and 12.9 for OS (p=0.002). TMTV
also identified a group of participants
with negative iPET2 (n=237; 92%)
who ultimately had a poor prognosis
(HR for PFS=4.6; p=0.0009 and HR
for OS=0.02; p value not reported).
Also, patients with a negative iPET2
and a high baseline TMTV had a
five-year PFS of 82 percent, com-
pared with 95 percent for those with
low baseline TMTV.
The study demonstrates the
“value of TMTV, an imaging
biomarker [that is] available at
diagnosis, measurable in early-stage
HL, and superior to the clinical and
biologic parameters already used,”
the researchers concluded.
The study is limited by a small
number of patients in each risk
group. The results of the study should
also be validated in another indepen-
dent data set, and “if these data are
confirmed, they may help to design
new response-adapted therapeutic
strategies,” the authors noted.
Chugai Pharmaceutical provided
support for the study.
The authors report no financial
conflicts.
REFERENCE
Cottereau AS, Versari A, Loft A, et al. Prognostic value of
baseline metabolic tumor volume in early stage Hodgkin’s
lymphoma in the standard arm of H10 trial. Blood. 2018
January 23. [Epub ahead of print]
Univariate Analysis for Baseline Prognostic Survival Factors
Prognostic Factor
Progression-Free Survival
Overall Survival
HR
(95% CI) p Value HR
(95% CI) p Value
Male 1.3
(0.6-2.7) 0.53 0.7
(0.2-2.3) 0.60
Age ≥50 years 1.8
(0.6-5.6) 0.18 2.2
(0.4-11.4) 0.23
Mixed cellularity 0.8
(0.3-2.2) 0.68 1.1
(0.2-4.8) 0.92
Presence of B symptoms 2.9
(1.3-6.7) 0.0035 4.6
(1.3-15.6) 0.006
≥4 involved sites 2.7
(0.7-9.5) 0.028 4.7
(0.7-31.5) 0.006
Bulk mediastinum (≥0.35) –
(0.9-5.7) 0.026 2.3
(0.6-8.9) 0.13
TMTV >147 cm 3 5.2
(1.8-14.7) <0.0001 7.2
(1.6-33.4) 0.0001
Unfavorable EORTC 5.7
(2.7-12.3) 0.0013 Not reached 0.0039
Unfavorable GHSG 2.8
(1.3-6.3) 0.046 5.3
(1.6-17.6) 0.075
Unfavorable NCCN 3.6
(1.7-7.9) 0.011 6.7
(2.1-21.6) 0.034
12.0
(2.3-63.7) <0.0001 13.2
(1.4-128.3) <0.0001
Positive iPET2 (defined as DS 4-5)
HR = hazard ratio; TMTV = total metabolic tumor volume; EORTC = European Organisation for Research and Treatment of Cancer; GHSG = German Hodgkin Study
Group; NCCN = National Comprehensive Cancer Network; iPET2 = interim positron emission tomography response after two treatment cycles; DS = Deauville scale
28
ASH Clinical News
Treatment With
Blinatumomab
Eradicates MRD in
Patients With ALL
More than three-quarters of patients
with acute lymphocytic leukemia (ALL)
who were in complete remission (CR)
following chemotherapy but still had
evidence of minimal residual disease
(MRD) achieved complete MRD
response following treatment with
blinatumomab, according to a phase
II study published in Blood. Nicola
Gökbuget, MD, of Goethe University
Hospital in Frankfurt, Germany, and
co-authors also determined that these
deeper responses were associated with
improved overall survival (OS).
“MRD persistence or recurrence [after
induction/consolidation chemotherapy] is
the most important risk factor for he-
matologic relapse in T- and B-cell ALL,”
the authors explained. “Targeted agents
with alternative mechanisms of action
may reduce MRD and delay or prevent
hematologic relapse.” Blinatumomab is a
bispecific T-cell engager antibody construct
that directs T cells to CD19-positive cells,
an antigen that is expressed on blast cells
in more than 95 percent of B-cell precursor