However, GSK2857916 is an off-the-shelf product and does
not have the risks of cytokine-release syndrome or neurotox-
icity present with BCMA CAR T cells or BITEs, she added.
While substantially less toxic, PFS appears somewhat shorter
than early results from trials of CAR T-cell therapies.
The “necessarily small sample size” represents an inherent
limitation of this analysis, the researchers wrote. In addition,
the lack of a comparator control, such as placebo, and the
lack of randomization are additional limitations of this initial
study. Corneal toxicity may be problematic in some patients.
“As these data are based on interim analyses of a phase I
study, we’re looking forward to the final analyses after longer
follow-up,” Dr. Trudel added. “Larger-scale and later-phase
clinical trials that explore the role of GSK2857916 as part of
combination therapy for RRMM are also greatly anticipated.”
The authors report relationships with GlaxoSmithKline,
which supported the study.
REFERENCE
Trudel S, Lendvai N, Popat R, et al. Targeting B-cell maturation antigen with
GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma
(BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol.
2018;19:1641-53.
Study of Single-Agent Nivolumab in Patients With
Relapsed/Refractory DLBCL Fails to Meet Endpoint
Treatment with single-agent nivolumab was associated
with “disappointingly low” response rates in patients
with relapsed or refractory diffuse large B-cell lymphoma
(DLBCL), according to results from a phase II trial published
in the Journal of Clinical Oncology.
Nivolumab, an anti–PD-1 monoclonal antibody, initially
demonstrated a promising preliminary response rate in earlier
phase I trials, but the drug failed to meet its primary endpoint
in the phase II trial, suggesting that patients with relapsed/
refractory disease or who are ineligible for transplant may fare
better with other treatment approaches.
In this open-label trial, the authors, led by Stephen Ansell,
MD, PhD, from the Mayo Clinic in Rochester, Minnesota,
evaluated nivolumab 3 mg/kg (administered intravenously
over 60 minutes, every 2 weeks) in 121 patients. Participants
had failed treatment with autologous hematopoietic cell
transplantation (n=87) or were ineligible for transplantation
(n=34). The researchers observed that patients in the prior
transplant group were young and had higher baseline per-
formance status scores than those who were ineligible for
transplant. The median number of prior lines of therapy was
three in each group (range not provided).
After a median follow-up of nine months (range = 0.1-2.5
months) in the prior-transplant group and six months (range
= 0.2-2.4 months) in the transplant-ineligible group, the over-
all response rates (defined as partial remission or better) were
10 percent and 3 percent, respectively. The median durations
of response were 11 and eight months (ranges not reported).
Three patients (all of whom were in the prior-transplant
group) achieved a complete remission that lasted for at least
11 months, the authors added. In the transplant-ineligible
group, the best response was in one patient who achieved a
partial remission that lasted for 8.3 months.
Patients in the prior-transplant group also appeared to have
better efficacy outcomes in terms of median progression-free
survival (1.9 months vs. 1.4 months) and median overall sur-
vival (12.2 months vs. 5.8 months; p values not reported).
The researchers also attempted to assess outcomes with
nivolumab for patients with genetic alterations in 9p24.1, a
potential biomarker indicating disease that is likely to respond
to PD-1 blockade, but these mutations were infrequent in this
population.
Treatment-related grade 3 and 4 adverse events were re-
ported in 24% of patients. The most common were neutrope-
nia (4%), thrombocytopenia (3%), and increased lipase (3%).
Of all evaluable samples for 9p24.1 analysis, 16% exhibited
low-level copy gain and 3% had amplification.
Seventy-eight patients died during the study, although
none of the deaths were attributed to nivolumab treatment.
Given the negative results in this study, the researchers
concluded that future studies should focus on combina-
tions of immunotherapies, beyond PD-1 blockade alone. As
a limitation of the study, the authors noted that this was a
small population, with a small proportion of patients with the
9p24.1 genetic alteration, who are more likely to benefit from
PD-1-inhibitor treatment.
The authors report relationships with Bristol-Myers Squibb,
the manufacturer of nivolumab, which sponsored the trial.
REFERENCE
Ansell SM, Minnema MC, Johnson P, et al. Nivolumab for relapsed/refractory
diffuse large B-cell lymphoma in patients ineligible for or having failed autologous
transplantation: a single-arm, phase II study. J Clin Oncol. 2019;37:481-489.
March 2019
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