NEWLY APPROVED DRUGS
The Year in FDA Approvals
In the past year, the FDA approved a record-breaking number of
drugs, several of which were indicated for the treatment of lymphoid
and plasma cell malignancies. Here, we review the regulatory approvals
since our last “Focus on Lymphoid Malignancies” special edition pub-
lished in March 2019. The list includes two new biosimilar versions of
commonly used drugs and a treatment approved as part of the FDA’s
Project Orbis, a new framework that allows for concurrent review of
cancer therapies with the agency’s international partners.
Polatuzumab vedotin-piiq
On June 10, 2019, the FDA approved the CD79b-directed
antibody drug conjugate polatuzumab vedotin-piiq, in
combination with bendamustine and rituximab (BR), to
treat adults with relapsed or refractory diffuse large B-cell
lymphoma (DLBCL) who have received at least two prior
therapies.
The approval was based on results from an open-label,
multicenter clinical trial that enrolled 80 adult patients
and randomized patients 1:1 to receive either BR alone or
BR with polatuzumab vedotin-piiq for six 21-day cycles.
All participants received rituximab 375 mg/m 2 on day 1 of
each cycle, plus bendamustine 90 mg/m 2 on days 2-3 of
cycle 1 and on days 1-2 of subsequent cycles; in the polatu-
zumab + BR group, participants also received polatuzumab
vedotin-piiq, 1.8 mg/kg by intravenous infusion on day 2 of
cycle 1 and on day 1 of subsequent cycles.
The complete response (CR) rate, the study’s prima-
ry endpoint, was 40% in the polatuzumab + BR group,
compared with 18% in the BR-alone group. The overall
response rate (ORR; including CRs and partial respons-
es) was also higher with polatuzumab: 63% versus 25%.
Among the 25 patients who responded to treatment with
polatuzumab + BR, 16 (64%) had response durations ≥6
months and 12 (48%) had response durations ≥12 months.
The most common adverse events (AEs; occurring
in ≥20% of patients) in the polatuzumab group includ-
ed neutropenia, thrombocytopenia, anemia, peripheral
neuropathy, fatigue, diarrhea, pyrexia, decreased appetite,
and pneumonia. Serious AEs occurred in 64% of patients,
most often from infection. Cytopenias (seen in 18% of
patients) were the most common reason for treatment
discontinuation.
Polatuzumab vedotin-piiq was approved with priority
review, breakthrough therapy, and orphan drug designa-
tions.
Selinexor
On July 3, 2019, selinexor, an oral selective inhibitor of
nuclear export (SINE), received accelerated approval for
patients with relapsed/refractory multiple myeloma (MM)
who have received four or more prior therapies and whose
disease has not responded to treatment with two or more
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Focus on Lymphoid & Plasma Cell Malignancies
proteasome inhibitors or immunomodulatory agents.
The FDA’s approval decision was based on its review
of safety and efficacy data from a prespecified subgroup
analysis of the single-arm, open-label, phase II STORM
trial, which included 83 patients with heavily pretreated
MM. The ORR was 25.3%, including one stringent CR, four
very good partial responses, and 16 partial responses. The
median time to first response was 4 weeks (range = 1-10
weeks) and the median response duration was 3.8 months
(range = 2.3 to not estimable).
In February 2019, the FDA’s Oncologic Drugs Adviso-
ry Committee (ODAC) expressed concerns about these
trial data, and recommended delaying approval until the
results of the phase III BOSTON trial, which evaluated
the safety and efficacy of bortezomib plus low-dose
dexamethasone with or without selinexor, became avail-
able. While the ODAC panel noted that selinexor did not
demonstrate strong single-agent activity in the STORM
trial, the reviewers expressed concerns about trial safety
data.
In STORM, the most common AEs (occurring in ≥20%
of patients) included thrombocytopenia, fatigue, nausea,
anemia, decreased appetite, decreased weight, diarrhea,
vomiting, hyponatremia, neutropenia, leukopenia, consti-
pation, dyspnea, and upper respiratory tract infection.
Selinexor was approved with the FDA’s fast track and
orphan drug designation.
Biosimilar: Rituximab-pvvr
On July 24, 2019, the FDA approved rituximab-pvvr, a bio-
similar of rituximab (Rituxan), for the treatment of adults
with chronic lymphocytic leukemia (CLL) and non-Hodgkin
lymphoma. The agent also was approved for other indica-
tions of its reference product, including granulomatosis
with polyangiitis and microscopic polyangiitis.
Rituximab-pvvr is a cytolytic antibody biosimilar to
rituximab that targets the protein CD20 present on the
surface of B cells.
The FDA’s approval was based on a review of a clinical
comparative study that found no clinically meaningful dif-
ferences in the efficacy, safety, immunogenicity, pharmaco-
kinetics, and pharmacodynamics between rituximab-pvvr
and its reference product.
Like its reference product, rituximab-pvvr carries
a boxed warning for increased risks of the following:
fatal infusion-related reactions, severe skin and mouth
reactions, hepatitis B virus reactivation, and progressive
multifocal leukoencephalopathy.
Daratumumab
On September 26, 2019, the FDA approved the combi-
nation of daratumumab, bortezomib, thalidomide, and