On Location
International Myeloma Workshop
UPDATES IN MYELOMA
In the Era of Novel Agents, Has Early
Mortality in Older Patients Decreased?
t the 15th International Myeloma
Workshop, held September 23–
26, 2015, myeloma specialists
from around the world gathered in Rome, Italy, to discuss
advances in the biology and treatment of
multiple myeloma. Here, we share some of
the research highlights from the meeting,
including the benefit of autologous transplant with carfilzomib, a pooled analysis
of maintenance therapy in myeloma, and
an early study of marizomib in relapsed/
refractory disease.
While novel agents for the treatment of
multiple myeloma (MM) have improved
patient outcomes and extended survival,
these agents are also associated with toxicities such as cardiac complications, infections, vascular complications.
To assess the rate and the causes of
early toxic deaths in the novel treatment
era, Alessandra Larocca, MD, from the
University of Torino, Italy, and colleagues
studied early deaths in a series of patients
treated with novel agents from two phase III
trials evaluating bortezomib- and lenalidomide-based treatment combinations.
“Early mortality [or death within the first 24
months after diagnosis of MM] is due to the
effects of active disease, comorbidities, and
treatment-related complications,” wrote Dr.
Larocca and co-authors. “With conventional chemotherapy, early toxic deaths were 10
percent in the first two months.”
They analyzed data for 1,173 patients
with newly diagnosed MM who were
enrolled in the Gruppo Italiano Malattie
EMatologiche dell’Adulto (GIMEMA) and
European Myeloma Network (EMN) trials
from May 2006 to September 2012.
Overall, 511 patients received bortezomib-containing regimens and 662 patients
received lenalidomide-containing regimens.
A total of 1,146 patients started therapy
and could be evaluated in the current
analysis. The authors found that death
within 24 months of the start of therapy occurred in 207 patients (18%), among whom
61 (5%) died due to adverse events.
Twelve patients (1%) died due to toxicity within 60 days, and this rate increased
over time by one percent every six months.
The most common reasons for early toxic
deaths were:
• Cardiac complications (30%; 18 patients)
• Infections (28%; 17 patients)
• Vascular complications (15%; 9 patients)
The researchers found that there was no
difference in the incidence of toxic deaths
according to treatment regimen, occurring in 31 patients (6%) who were treated
with bortezomib-containing regimens and
30 patients (6%) who were treated with
lenalidomide-containing regimens (p=0.32).
In addition, there was no difference in the
proportions of toxic events between the two
types of regimens.
Dr. Larocca and colleagues identified
two factors that were associated with a
higher incidence of early toxic death: age
46
ASH Clinical News
>80 years (hazard ratio [HR] = 1.09 per
1-year increase; p=0.002) and tumor burden
defined by the International Staging System
(ISS) stage (ISS 2 vs. ISS 1: HR=3.81; p=0.01
and ISS 3 vs. ISS 1: HR=5.69; p=0.002). Poor
performance status, however, was not a predictor of early death (HR=1.25; p=0.59).
“Novel agents have substantially reduced
the risk of toxic deaths as compared to
conventional therapy,” Dr. Larocca and colleagues concluded. “Nevertheless, one-third
of early deaths occurred due to cumulative
specific drug-related toxicities. The two-fold
higher risk of toxic mortality in octogenarians indicates the need for a careful assessment of frailty to identify patients who may
benefit from a gentler approach.” ●
REFERENCE
Larocca A, Bringhen S, Petrucci MT, et al. Early mortality in elderly
patients with newly diagnosed multiple myeloma treated with novel
agents. Abstract OP-004. Presented at the 15th International Myeloma
Workshop, September 23, 2015; Rome, Italy.
Minimal Residual
Disease Status
Linked to Survival
Outcomes in
Multiple Myeloma
Although many patients with multiple myeloma (MM) achieve a complete response
(CR) with treatment, the likelihood of
relapse is still high, suggesting the presence of minimal residual disease (MRD)
that cannot be detected via conventional
assessments. The heterogeneity among
MRD detection techniques, though,
hinders their clinical interpretation. To assess the role MRD status plays in survival
outcomes for patients with MM, Nikhil C.
Munshi, MD, and colleagues conducted
a meta-analysis of 18 studies involving
patients with newly diagnosed MM.
Dr. Munshi, director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center at the Dana-Farber
Cancer Institute in Boston, Massachusetts,
presented these data at the 15th International Myeloma Workshop.
To identify the published articles for
the meta-analysis, Dr. Munshi and col-
November 2015