Literature Scan
The Ins and Outs of Inclusion Criteria
for Myeloma Clinical Trials
Clinical trial protocols often incorporate
strict eligibility criteria to maximize
reproducible, results with minimal risk to
trial participants. Unfortunately, restricting
a trial’s patient population may result in
outcomes that are not generalizable
to “real-world” patients, according
to a report published in Clinical
Lymphoma, Myeloma & Leukemia.
In the Connect MM Registry
study, Jatin J. Shah, MD, of the
Department of Lymphoma/Myeloma
at the MD Anderson Cancer Center
in Houston, Texas, and co-authors
reviewed eligibility criteria of recent
randomized, controlled trials (RCTs)
of patients with newly diagnosed
myeloma to determine whether
the criteria were too strict, and
whether the populations enrolled
accurately reflected their real-world
counterparts.
The multicenter, prospective,
observational cohort study included
1,406 adult patients (median age =
67 years; range = 24-94 years) who
satisfied the minimum eligibility
requirements to participate in an
RCT (i.e., meeting calcium elevation,
renal insufficiency, anemia, and lytic
bone lesion [CRAB] criteria). All pa-
tients had symptomatic disease and
were diagnosed within two months
of enrollment (between September
28, 2009, and December 14, 2011).
Patients were treated according to
standard practice at each of the 250
study sites.
To identify common eligibility
criteria, the authors searched PubMed
for phase III myeloma clinical trials
conducted in the past 10 years,
including studies of thalidomide,
lenalidomide, and bortezomib. Studies
of relapsed/refractory disease, studies
of supportive care treatments, and
secondary reports were excluded. The
authors found 24 RCTs, all of which
had the following exclusion criteria:
• absence of measurable disease
• grade >2 peripheral neuropathy
• Eastern Cooperative Oncology
Group (ECOG) performance
status score of 3 or 4
• a history of myelodysplastic
syndromes, other hematologic
malignancies, or solid tumors
Applying these common criteria
to the unselected Connect MM
Registry, 563 (40%) of the patients
58
ASH Clinical News
would be considered ineligible for RCTs.
If exclusion criteria were more aggressive,
to include M-protein (≤1.0 g/dL) and
hemoglobin (≤8 g/dL) criteria, as many
as 56.8 percent of patients would be
ineligible for inclusion.
The researchers then compared patient
characteristics between those who were
RCT-ineligible (n=563) and those who
were RCT-eligible (n=843). Significantly
more RCT-ineligible patients had
hypercalcemia (11.0% vs. 5.5%; p<0.001),
creatinine levels >2.0 mg/dL (38.9% vs.
6.2%; p<0.001), and low hemoglobin levels
(59.5% vs. 39.5%; p<0.001).
Most patients received a bortezomib-
containing regimen as initial therapy
in both the RCT-ineligible and -eligible
cohorts (72.5% vs. 70.7%; p=0.842), but
RCT-ineligible patients were less likely to
receive lenalidomide (40.5% vs. 49.7%;
BOSULIF® (bosutinib) is indicated for the treatment of adult patients with chronic, accelerated, or blast phase
Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to
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