Literature Scan
relapsed/refractory MM who had received
at least one prior line of therapy or
were refractory to initial treatment. All
patients were bortezomib-naïve and had
not received prior doxorubicin or other
anthracycline exposure >240 mg/m2.
Patients were randomized 1:1 to
receive:
• Bortezomib 1.3 mg/m2 intravenously
on days 1, 4, 8, and 11 of every
21-day cycle (n=322)
salvage therapies in the combination
and monotherapy cohorts included
dexamethasone (47% vs. 51%), thalidomide (31% vs. 31%), cyclophosphamide
(26% vs. 31%), melphalan (24% vs.
22%), lenalidomide (23% vs. 21%), bortezomib (23% vs. 18%), and doxorubicin
(6% vs. 11%).
“The inability to sustain the observed
early survival advantage may have been
caused by the effects of subsequent lines
of therapy,” Dr. Orlowski and colleagues
wrote, also noting that the study results were
limited by the initial study design, which
set a median survival of just 20 months in
the bortezomib monotherapy group. “[That
number] was exceeded by 50 percent, suggesting the benefits of novel agents.”
The number of effective salvage
therapy options now available to MM
patients, the authors added, “presents a
practical challenge of having adequate
power for long-term survival as a primary
endpoint.”
REFERENCE
Orlowski RZ, Nagler A, Sonneveld P, et al. Final overall survival results
of a randomized trial comparing bortezomib plus pegylated liposomal
doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma. Cancer. 2016 May 18. [Epub ahead of print]
• Bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8, and 11 of
every 21-day cycle, plus PLD 30
mg/m2 as a 1-hour intravenous
infusion on day 4 of each 21day cycle (n=324)
Treatment was continued until
disease progression, unacceptable
toxicity, or for up to eight treatment
cycles; patients who still responded
after eight cycles and had acceptable
tolerability could continue treatment.
Crossover from monotherapy to
combination therapy was not allowed
during the study.
At the clinical cut-off date (May
16, 2014) for the final survival
analysis, 79 percent of patients had
died: 253 (78%) in the bortezomibPLD cohort and 257 (80%) in the
bortezomib monotherapy cohort.
Six percent of patients withdrew
consent, four percent were lost to
follow-up, and 11 percent were still
alive: 37 patients (11%) in the combination cohort and 34 (11%) in the
monotherapy group.
After a median follow-up of
8.6 years, OS in the bortezomibPLD cohort was 33 months (95%
CI 28.9-37.1) compared with 30.8
months (95% CI 25.2-36.5) in the
bortezomib monotherapy group.
The two-month difference in OS
was not statistically significant
(hazard ratio [HR] = 1.047; 95%
CI 0.879-1.246; p=0.6068). In the
interim analysis, Dr. Orlowski and
co-authors noted, the early OS benefit for bortezomib-PLD therapy
over bortezomib monotherapy was
significantly higher (HR=1.41; 95%
CI 1.002-1.97; p=0.047).
Results from subgroup analyses
were similar and generally consistent,
though there was a small, non-significant trend in favor of the combination therapy among women, patients
≥65 years, and those who had an
ECOG status of 0 or cytogenetic
abnormalities.
The majority of patients in both
the bortezomib-PLD group and the
bortezomib monotherapy group
received salvage therapy (78%
and 80%, respectively). The most
frequently used (>10% of patients)
34
ASH Clinical News
EXTEND EFFICACY.
EXTEND THE POSSIBILITIES.
NINLARO is indicated in combination with lenalidomide
and dexamethasone for the treatment of patients with
multiple myeloma who have received at least one
prior therapy.
IMPORTANT SAFETY INFORMATION FOR NINLARO
WARNINGS AND PRECAUTIONS
• Thrombocytopenia has been reported with NINLARO.
During treatment, monitor platelet counts at least monthly,
and consider more frequent monitoring during the first
three cycles. Manage thrombocytopenia with dose
modifications and platelet transfusions as per standard
medical guidelines. Adjust dosing as needed. Platelet
nadirs occurred between Days 14-21 of each 28-day cycle
and recovered to baseline by the start of the next cycle.
• Gastrointestinal Toxicities, including diarrhea, constipation,
nausea and vomiting, were reported with NINLARO and may
occasionally require the use of antidiarrheal and antiemetic
medications, and supportive care. Diarrhea resulted in the
discontinuation of one or more of the three drugs in 1% of
patients in the NINLARO regimen and < 1% of patients in
the placebo regimen. Adjust dosing for severe symptoms.
• Peripheral Neuropathy (predominantly sensory) was
reported with NINLARO. The most commonly reported
reaction was peripheral sensory neuropathy (19% and 14%
in the NINLARO and placebo regimens, respectively).
Peripheral motor neuropathy was not commonly reported
in either regimen (< 1%). Peripheral neuropathy resulted in
discontinuation of one or more of the three drugs in 1% of
patients in both regimens. Monitor patients for symptoms
of peripheral neuropathy and adjust dosing as needed.
• Peripheral Edema was reported with NINLARO. Monitor
for fluid retention. Investigate for underlying causes when
appropriate and provide supportive care as necessary.
Adjust dosing of dexamethasone per its prescribing
information or NINLARO for Grade 3 or 4 symptoms.
• Cutaneous Reactions: Rash, most commonly maculopapular and macular rash, was reported with NINLARO.
Rash resulted in discontinuation of one or more of the
three drugs in < 1% of patients in both regimens. Manage
rash with supportive care or with dose modification.
• Hepatotoxicity has been reported with NINLARO.
Drug-induced liver injury, hepatocellular injury, hepatic
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommends