IN THE LITERATURE
Together, these safety and efficacy results suggest that
“isatuximab is an important new treatment option for the
management of relapsed and refractory myeloma, particu-
larly for patients who become refractory to lenalidomide and
a PI,” the authors concluded. However, the study’s findings
are limited by its open-label design, which introduces the
potential for bias in primary outcome reporting. Also, be-
cause ICARIA-MM did not enroll patients with disease that
was refractory to another anti-CD38 antibody, these results
are not applicable to this subgroup of patients.
Study authors report relationships with Sanofi, which
sponsored the trial.
Reference
Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose
dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and
refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study.
Lancet. 2019;394:2096-2107.
Outcomes With Idelalisib Differ in the Clinical Trial
Versus Real-World Setting
According to a real-world analysis published in JAMA Oncology,
treatment outcomes with idelalisib differed between patients with
follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)
treated in the clinical setting or in a clinical trial, with Medicare
beneficiaries faring worse than their clinical trial counterparts.
The differences could be attributed to selective eligibility criteria
and frequent dose reductions in clinical trials, the authors, led by
Steven T. Bird, PhD, PharmD, MS, from the FDA’s Office of
Pharmacovigilance and Epidemiology, noted.
• CLL: 89 trial participants (mean age = 74 years) and 294
Medicare beneficiaries (mean age = 76 years) The median treatment duration was shorter for real-
world patients with CLL compared with clinical trial partic-
ipants (173 days vs. 473 days; p<0.001); however, there was
no significant difference in the FL cohort (114 days vs. 160
days; p=0.38). This could be related to the fact that there
were higher rates of idelalisib dose reductions in the trial
setting: 32.6% versus 18.0% for CLL (p=0.003) and 38.5%
versus 16.1% for FL (p=0.02).
Compared with trial participants, Medicare beneficia-
ries in both disease cohorts had higher mortality rates (CLL:
HR=1.40 [95% CI 0.93-2.11]; FL: HR=1.39 [95% CI 0.69-
2.78]), as well as higher rates of fatal infections per 100
person-years (CLL: 18.4 vs. 9.8 [p=0.04]; FL: 27.6 vs. 18.6
[p=0.54). Among Medicare beneficiaries, an infection
requiring hospitalization within 6 months of idelalisib
treatment increased the risk of on-treatment fatal infec-
tions more than twofold. Ten of the serious on-treatment
infections had Pneumocystis jirovecii pneumonia (PJP) listed
as a contributory cause. Four of these infections were fatal;
in the fatal cases, no PJP prophylaxis had been given (pro-
phylaxis is recommended in the prescribing instructions).
These findings suggest that the data observed in clin-
ical trials of patients treated with idelalisib may not be
generalizable to clinical practice. “Efficacy and tolerabil-
ity may be meaningfully different for optimally selected
and closely monitored trial participants compared with
unrestricted patients in the clinical setting,” the authors
concluded. “Compliance with [infection] prophylaxis and
close monitoring of absolute neutrophil counts, with
appropriate dose interruptions and reductions, may help
reduce the rate of serious infections [for real-world pa-
tients],” the researchers concluded.
The authors report no relevant conflicts of interest.
“Medicare beneficiaries were older and sicker and had un-
favorable imbalances in treatment duration, mortality, and
fatal infections compared with clinical trial participants,”
the authors reported. Reference
Bird ST, Tian F, Flowers N, et al. Idelalisib for treatment of relapsed follicular lymphoma and chronic
lymphocytic leukemia: a comparison of treatment outcomes in clinical trial participants vs
Medicare beneficiaries. JAMA Oncol. 2019 December 19. [Epub ahead of print]
“Idelalisib is approved as monotherapy in relapsed follicular
lymphoma and with rituximab for relapsed chronic lym-
phocytic leukemia,” the authors explained. “Toxic effects
can be severe and treatment-limiting, [and] outcomes in a
real-world population are not yet characterized.”
With this analysis, investigators compared idelalisib
treatment outcomes in the clinical setting with outcomes
reported in clinical trial data of patients with FL and CLL.
Treatment duration, on-treatment mortality, overall mor-
tality, and serious and fatal infections were compared be-
tween real-world patients and participants in two trials – a
single-group, open-label phase II trial supporting idelalis-
ib’s approval for relapsed or refractory FL and a randomized,
double-blind phase III trial supporting approval of idelalisib
plus rituximab for relapsed CLL.
The study included 115 clinical trial participants and 599
Medicare beneficiaries aged 65 years or older:
• FL: 26 trial participants (mean age = 73 years) and 305
Medicare beneficiaries (mean age = 76 years)
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Focus on Lymphoid & Plasma Cell Malignancies