FDA ONCOLOGY UPDATE
New Oncology Drugs/Indications Approved
by the FDA
This section provides a brief overview of new cancer drugs and new indications
approved by the FDA between February 4, 2021, and March 30, 2021.
NEW DRUGS
Abecma First CAR T-Cell Therapy
Approved for Multiple Myeloma
On March 27, 2021, the FDA ap­proved idecabtagene
vicleucel (Abecma; Bristol Myers Squibb/Bluebird Bio),
a B-cell maturation antigen (BCMA)-­directed, genet-
ically modified autologous chimeric antigen receptor
(CAR) T-cell therapy, for the treatment of adults
with multiple myeloma whose disease did not respond
to, or recurred, after ≥4 lines of therapy.
Idecabtagene vicleucel is the first BCMA-directed
CAR T-cell therapy approved for the treatment of
multiple myeloma. The FDA granted this indication
orphan drug and breakthrough therapy designations.
“While there is no cure for multiple
myeloma, the long-term outlook can
vary….Today’s approval provides a new
treatment option for patients who
have this uncommon type of cancer.”
—Peter Marks, MD, PhD
“While there is no cure for multiple myeloma, the
long-term outlook can vary based on the individual’s age
and the stage of the condition at the time of diagnosis.
Today’s approval provides a new treatment option for
patients who have this uncommon type of cancer,” said
Peter Marks, MD, PhD, Director of the FDA’s Center for
Biologics Evaluation and Research.
According to the National Cancer Institute, in 2020
multiple myeloma accounted for approximately 1.8%
(N = 32,000) of all new cancer cases in the United States.
The FDA approved idecabtagene vicleucel based on
results of a multicenter study of 127 patients with re-
lapsed or refractory multiple myeloma after ≥3 lines of
therapy. Approximately 88% of the patients had re-
ceived ≥4 lines of therapy.
Overall, 72% of patients had a response to the study
drug, including 28% complete responses. Of the pa-
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tients with complete responses, 65% had a complete
response lasting ≥12 months.
The most common side effects of idecabtagene vic-
leucel include cytokine release syndrome (CRS), in-
fections, fatigue, musculoskeletal pain, and a weak-
ened immune system. Side effects usually appear
within the first 1 or 2 weeks after treatment, but some
may occur later.
Severe side effects associated with idecabtagene vic-
leucel include CRS, hemophagocytic lymphohistiocyto-
sis or macrophage activation syndrome, neurologic ad-
verse events, and prolonged cytopenia, all of which can
be fatal or life-threatening. Because of such serious side
effects, idecabtagene vicleucel is only available through
a REMS program. The FDA is also requiring the manu-
facturer to conduct a postmarketing observational study
to validate the long-term safety of the drug.
FDA Approved Pepaxto for Relapsed or
Refractory Multiple Myeloma
On February 26, 2021, the FDA accelerated the ap-
proval of melphalan flufenamide (Pepaxto; Oncopep-
tides AB), an alkylating drug, for the treatment, in
combination with dexamethasone, of adults with re-
lapsed or refractory multiple myeloma who have received
≥4 lines of therapy and whose disease is triple-­refractory
to ≥1 proteasome inhibitors, 1 immuno­modulatory drug,
and 1 CD-38–directed monoclonal antibody.
Melphalan flufenamide is the first peptide–drug con-
jugate approved for the treatment of multiple myeloma.
The FDA granted it a priority review and an orphan
drug designation for this indication.
“Research has shown melphalan flufenamide to be a
novel and innovative therapeutic option, which is ac-
tive in refractory disease and has manageable toxicity,
with the convenience of being administered by infusion
once a month,” said Paul G. Richardson, MD, Director
of Clinical Research at the Jerome Lipper Multiple
Myeloma Center, Dana-­Farber Cancer Institute. “Based
on our findings, melphalan flufenamide is an important
addition to the treatment armamentarium, with the
potential to meaningfully improve outcomes in an area
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 FDA ONCOLOGY UPDATE
of important unmet medical need.”
The FDA approval was based on results from the
multicenter, single-arm HORIZON clinical trial. Of
157 patients with relapsed or refractory multiple myelo-
ma, 97 patients had triple-refractory disease and had
received ≥4 lines of therapy. The FDA approval was
based on the subpopulation of 97 patients. Patients re-
ceived intravenous melphalan flufenamide 40 mg on
day 1 and oral dexamethasone 40 mg on days 1, 8, 15,
and 22 of every 28-day cycle, until disease progression
or until unacceptable toxicity.
“Research has shown melphalan
flufenamide to be a novel and
innovative therapeutic option, which is
active in refractory disease and has
manageable toxicity, with the
convenience of being administered by
infusion once a month.”
—Paul G. Richardson, MD
The main efficacy outcome measures were overall
response rate (ORR) and duration of response (DOR).
The ORR in the subgroup was 23.7% (95% confidence
interval [CI], 15.7-33.4), and the median DOR was 4.2
months (95% CI, 3.2-7.6).
The safety of melphalan flufenamide was evaluated
in the total study population of 157 patients. The most
common (>20%) adverse reactions were fatigue, nau-
sea, diarrhea, pyrexia, and respiratory tract infection.
The most common (≥50%) laboratory abnormalities
were decreased leukocytes, platelets, lymphocytes, neu-
trophils, and hemoglobin, and increased creatinine.
Cosela First CDK4/6 Inhibitor FDA
Approved to Reduce Chemotherapy-
Induced Myelosuppression
On February 12, 2021, the FDA approved trilaci-
clib (Cosela; G1 Therapeutics), as a first-in-class cyclin-­
dependent kinase (CDK)4/6 inhibitor to reduce the
frequency of chemotherapy-induced myelosuppression
in adults with extensive-stage small-cell lung cancer,
when used before a platinum plus etoposide regimen or
a topotecan-containing regimen. Trilaciclib may pre-
vent damage to bone marrow cells by inhibiting the
CDK4/6 enzyme. The FDA granted trilaciclib priority
review and a breakthrough therapy designation.
“For patients with extensive-stage small-cell lung
cancer, protecting bone marrow function may help
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106 Journal of Hematology Oncology Pharmacy l www.JHOPonline.com
make their chemotherapy safer and allow them to com-
plete their course of treatment on time and according
to plan,” said Albert Deisseroth, MD, PhD, Supervisory
Medical Officer at the FDA’s Center for Drug Evalua-
tion and Research. “Today’s approval of Cosela will
give patients a treatment option that can reduce the
occurrence of a common, harmful side effect of chemo-
therapy.”
The FDA approved trilaciclib based on data from 3
randomized, double-­ blind, placebo-controlled studies
with a total of 245 patients who were randomized to in-
travenous trilaciclib or to placebo before chemotherapy.
The study compared the incidence rate and duration of
severe neutropenia in the first cycle of chemotherapy.
In all 3 studies, patients who received trilaciclib had
a lower risk for severe neutropenia than those who re-
ceived placebo, as well as a shorter duration of severe
neutropenia.
“Today’s approval of Cosela will give
patients a treatment option that can
reduce the occurrence of a common,
harmful side effect of chemotherapy.”
—Albert Deisseroth, MD, PhD
The most common (≥10%) adverse events were fa-
tigue, increased levels of aspartate aminotransferase,
headache, pneumonia, and deficiencies in calcium, po-
tassium, and phosphate. The grade 3 or 4 hematologic
adverse reactions to trilaciclib included neutropenia
(32%), thrombocytopenia (18%), anemia (16%), leuko­
penia (4%), and febrile neutropenia (3%). Trilaciclib
therapy is associated with the risk for acute drug hyper-
sensitivity, interstitial lung disease, and pneumonitis.
FDA Approved Breyanzi, Novel CAR T-Cell
Therapy, for Large B-Cell Lymphoma
On February 5, 2021, the FDA approved lisocabta-
gene maraleucel (Breyanzi; Juno Therapeutics), a new
CD19-­ directed chimeric antigen receptor (CAR)
T-cell therapy, for the treatment of adults with relapsed
or refractory large B-cell lymphoma (LBCL) after ≥2
previous lines of systemic therapy. The FDA granted
lisocabtagene maraleucel priority review, as well as
breakthrough therapy, orphan drug, and regenerative
medicine advanced therapy designations.
“Today’s approval represents another milestone in the
rapidly progressing field of gene therapy by providing an
additional treatment option for adults with certain types
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 FDA ONCOLOGY UPDATE
of cancer affecting the blood, bone marrow, and lymph
nodes,” said Peter Marks, MD, PhD, Director of the
FDA’s Center for Biologics Evaluation and Research.
This approval was based on data from the single-arm,
open-label, multicenter TRANSCEND clinical trial of
192 adults with relapsed or refractory LBCL who had
received lymphodepleting chemotherapy and ≥2 lines
of therapy.
“Today’s approval represents another
milestone in the rapidly progressing
field of gene therapy.”
—Peter Marks, MD, PhD
The overall response rate was 73% (95% confidence
interval [CI], 67-80), including 54% (N = 104) com-
plete responses (95% CI, 47-61). The median time to
first response was 1 month. Of those who had a com-
plete response, the duration of response (DOR) was ≥6
months in 65% and ≥9 months in 62%. The median
DOR was 1.4 months in the patients with a partial re-
sponse and was not reached in those with complete
responses (95% CI, 16.7-not reached).
The most common (46%) adverse event was cyto-
kine release syndrome (CRS), and 35% of all patients
had a neurologic adverse event (grade ≥3, 12%), in-
cluding 3 fatal cases. Other grade ≥3 adverse reactions
included cytopenia (31%) and infection (19%). Be-
cause lisocabtagene maraleucel is associated with a risk
for life-threatening CRS and other neurologic effects,
the drug is only available through a REMS program.
Ukoniq, New Targeted Therapy, FDA
Approved for Marginal-Zone and
Follicular Lymphoma
On February 5, 2021, the FDA approved umbralisib
(Ukoniq; TG Therapeutics), an oral kinase inhibitor,
for the treatment of adults with relapsed or refractory
marginal-zone lymphoma (MZL) or with relapsed or
refractory follicular lymphoma (FL). Umbralisib is indi-
cated for MZL after ≥1 CD20-directed regimens, and
for FL after ≥3 lines of systemic therapy.
Umbralisib is the first dual inhibitor of PI3K-delta
and CK1-epsilon to be approved by the FDA, which
granted it priority review for MZL and an orphan drug
designation for MZL and FL.
“MZL and FL remain incurable diseases, with limited
treatment options for patients who relapse after previ-
ous therapy and no defined standard of care. With the
approval of umbralisib we now have a targeted, oral,
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Vol 11 | No 2 l April 2021 www.JHOPonline.com
once daily option, offering a needed treatment alterna-
tive for patients,” said Nathan H. Fowler, MD, Profes-
sor of Medicine, The University of Texas M.D. Ander-
son Cancer Center.
This FDA approval of umbralisib was based on 2
single-arm cohorts of the open-label, multicenter
UNITY clinical trial that included 69 patients with
MZL and 117 patients with FL who have received sev-
eral lines of previous therapy. In the study, all patients
received oral umbralisib 800 mg once daily until disease
progression or until unacceptable toxicity. The efficacy
outcome measures were overall response rate (ORR)
and duration of response (DOR).
“MZL and FL remain incurable diseases,
with limited treatment options for
patients who relapse after previous
therapy….With the approval of
umbralisib we now have a targeted,
oral, once daily option.”
—Nathan H. Fowler, MD
The ORR was 49% among the patients with MZL
(95% confidence interval [CI], 37-61.6), with 16%
reaching a complete response; the median DOR was not
reached (95% CI, 9.3-not estimable). In the patients
with FL, the ORR was 43% (95% CI, 33.6-52.2) and 3%
achieved a complete response; the median DOR was
11.1 months (95% CI, 8.3-16.4).
The most common (≥15%) adverse reactions with
umbralisib were increased creatinine, diarrhea/colitis,
fatigue, nausea, neutropenia, transaminase elevation,
musculoskeletal pain, anemia, thrombocytopenia,
upper respiratory tract infection, vomiting, abdominal
pain, decreased appetite, and rash.
Serious adverse reactions occurred in 18% of pa-
tients, and most often resulted from diarrhea/colitis and
infection. Diarrhea/colitis and transaminase elevation
were the most common reasons for dose modifications.
NEW INDICATIONS
Vyxeos Now Indicated for Pediatric
Patients with AML
On March 30, 2021, the FDA approved a new indi-
cation for daunorubicin and cytarabine (Vyxeos; Jazz
Pharmaceuticals) for the treatment of pediatric patients
aged ≥1 years with newly diagnosed, therapy-related
acute myeloid leukemia (AML) or patients with AML
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 FDA ONCOLOGY UPDATE
and myelodysplasia-related changes. Daunorubicin and
cytarabine is a liposomal combination of an anthracy-
cline topoisomerase inhibitor (daunorubicin) and a
nucleoside metabolic inhibitor (cytarabine).
The FDA has previously approved the combination
of daunorubicin and cytarabine for the treatment of
adults with newly diagnosed, therapy-related AML or
AML with myelodysplasia-related changes.
The FDA approved this new indication in pediatric
patients based on safety data from 2 single-arm clinical
trials: the AAML1421 study and the CPX-MA-1201
study, as well as on efficacy evidence shown in a previous
clinical trial in adults.
“The expansion of the Vyxeos label to include chil-
dren is a welcome and necessary advancement in sup-
port of some of our most vulnerable patients,” said Ed-
ward Anders Kolb, MD, Director of the Center for
Cancer and Blood Disorders at Nemours/Alfred I. Du-
Pont Hospital for Children, and Chair of the Myeloid
Disease Committee of the Children’s Oncology Group.
In all, 38 pediatric patients aged 1 year to 21 years
with AML who were in first relapse were enrolled in the
phase 1/2 AAML1421 study, and 27 patients aged 1 year
to 19 years with relapsed or refractory hematologic ma-
lignancies were enrolled in the phase 1 CPX-MA-1201
study. In both studies, no differences were found in the
safety profile of daunorubicin and cytarabine based on
the patients’ age.
The most common (≥25%) adverse reactions with
daunorubicin and cytarabine include bleeding events,
fever, rash, swelling, nausea, sores in the mouth or
throat, diarrhea, constipation, muscle pain, tiredness,
stomach pain, difficulty breathing, headache, cough,
decreased appetite, irregular heartbeat, pneumonia,
blood infection, chills, sleep disorders, and vomiting.
Yescarta First CAR T-Cell Therapy
Approved for Follicular Lymphoma
On March 5, 2021, the FDA approved a new indi-
cation for axicabtagene ciloleucel (Yescarta; Kite Phar-
ma), a chimeric antigen receptor (CAR) T-cell thera-
py, for the treatment of patients with relapsed or
refractory follicular lymphoma (FL) who have received
≥2 lines of systemic therapy. The FDA granted this in-
dication a priority review as well as breakthrough ther-
apy and orphan drug designations.
Axicabtagene ciloleucel was the first CAR T-cell
therapy to be approved by the FDA when it was ap-
proved for large B-cell lymphoma. The new approval
makes it the first CAR T-cell therapy for indolent FL.
“For follicular patients in the third line of therapy,
the 5-year survival rate is only 20%, highlighting the
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108 Journal of Hematology Oncology Pharmacy l www.JHOPonline.com
urgent need for treatments that offer a real chance for
durable remission. Impressively, 91% of follicular lym-
phoma patients in the ZUMA-5 study responded to a
single infusion of axicabtagene ci­loleucel, including an
estimated 74% of patients in a continued remission at
18 months,” said Caron A. Jacobson, MD, MMSc,
Medical Director, Immune Effector Cell Therapy Pro-
gram, Dana-Farber Cancer Institute.
“Impressively, 91% of follicular
lymphoma patients in the ZUMA-5
study responded to a single infusion of
axicabtagene ciloleucel, including an
estimated 74% of patients in a
continued remission at 18 months.”
—Caron A. Jacobson, MD, MMSc
The FDA approval was based on efficacy results from
the single-arm, open-label, multicenter ZUMA-5 clin-
ical trial of 146 patients with relapsed or refractory FL
who had received ≥2 lines of therapy; 81 of them were
evaluable for efficacy. Axicabtagene ciloleucel was ad-
ministered as a single infusion after lymphodepleting
chemotherapy.
The main efficacy measures were overall response
rate (ORR) and duration of response (DOR). The ORR
in the 81 evaluable patients was 91% (95% confidence
interval [CI], 83%-96%), including 60% complete re-
missions. The median time to response was 1 month,
the median DOR was not reached, and the 1-year rate
of ongoing remission was 76.2%. In the 146 total study
patients, the ORR was 89% (95% CI, 83%-94%), in-
cluding 62% complete responses.
The most common (≥20%) adverse reactions with
axicabtagene ciloleucel in this study were cytokine re-
lease syndrome, fever, hypotension, encephalopathy,
tachycardia, fatigue, headache, febrile neutropenia,
nausea, infection, decreased appetite, chills, diarrhea,
tremor, musculoskeletal pain, cough, hypoxia, consti-
pation, vomiting, arrhythmias, and dizziness.
Lorbrena Now FDA Approved
for First-Line Treatment of
Metastatic NSCLC
On March 3, 2021, the FDA approved a new indi-
cation for lorlatinib (Lorbrena; Pfizer), a third-genera-
tion ALK inhibitor, for the first-line treatment of pa-
tients with non–small-cell lung cancer (NSCLC) and
ALK mutation.
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 FDA ONCOLOGY UPDATE
The FDA has previously approved lorlatinib based
on the CROWN study for the second- or third-line
treatment of patients with ALK-positive NSCLC, as
detected by an FDA-approved test. This new indica-
tion also converts the previous accelerated approval to
a full approval.
The expanded indication for lorlatinib was based on
the results from the phase 3 CROWN clinical trial,
which compared lorlatinib and crizotinib (Xalkori) in
treatment-naïve patients with metastatic, ALK-­
positive NSCLC. The results showed a 72% reduction
(hazard ratio, 0.28; 95% confidence interval, 0.19-0.41;
P <.0001) in the risk for disease progression or death
with lorlatinib versus crizotinib.
“The CROWN data have shown Lorbrena can sig-
nificantly improve outcomes in the first-line treatment
of ALK-positive non-small cell lung cancer, including
those who present with brain metastases,” said Benja-
min Solomon, MD, Department of Medical Oncology,
Peter MacCallum Cancer Centre. “This approval is
meaningful for my patients, because we now have a
highly effective treatment option that can delay the
progression of a typically aggressive disease.”
The most common (≥20%) adverse events of any
grade with lorlatinib were edema, weight gain, periph-
eral neuropathy, cognitive effects, diarrhea, dyspnea,
and hypertriglyceridemia. Treatment discontinuation
because of adverse events occurred in 6.7% of people.
Libtayo Receives 2 New Indications: For
Basal-Cell Carcinoma and for NSCLC
On February 9, 2021, the FDA approved a new in-
dication for cemip­ limab-rwlc (Libtayo; Regeneron/
sanofi­-aventis) for the treatment of locally advanced or
metastatic basal-cell carcinoma (BCC) in patients who
had received or are ineligible to receive a hedgehog
inhibitor. The FDA granted cemiplimab a priority re-
view and accelerated its approval for this indication.
Cemiplimab was previously approved for metastatic or
locally advanced cutaneous squamous-cell carcinoma.
This FDA approval of cemiplimab for BCC was based
on results from Study 1620, a multicenter, nonrandom-
ized, open-label clinical trial of 84 patients with locally
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advanced BCC and 28 patients with metastatic BCC.
The main efficacy measures were objective response
rate (ORR) and duration of response (DOR).
The ORR was 29% (95% confidence interval [CI],
19-40) in those with locally advanced BCC, and the
median DOR was not reached; 79% of the patients
maintained their responses for ≥6 months. Among the
patients with metastatic BCC, the confirmed ORR was
21% (95% CI, 8-41), and the median DOR was not
reached; all the responders maintained their response
for ≥6 months.
The most common (≥20%) adverse reactions were
fatigue, musculoskeletal pain, diarrhea, rash, and pruri-
tus. Severe adverse reactions were immune-mediated
adverse reactions (ie, pneumonitis, hepatitis, colitis,
adrenal insufficiency, hypo- and hyperthyroidism, dia-
betes, and nephritis) and infusion reactions.
On February 22, 2021, the FDA approved cemi-
plimab for the first-line treatment of patients with ad-
vanced or metastatic non–small-cell lung cancer
(NSCLC) who are not candidates for resection or de-
finitive chemoradiation and whose tumors have high
PD-L1 expression and no EGFR, ALK, or ROS1 muta-
tions. The FDA granted this indication priority review.
The approval was based on data from Study 1624, a
multicenter, randomized, open-label clinical trial of
710 patients with metastatic NSCLC or patients with
advanced NSCLC who were not candidates for resec-
tion or chemoradiation. The patients were randomized
to cemiplimab 350 mg intravenously every 3 weeks for
108 weeks or to platinum-­based chemotherapy. The
main end points were overall survival (OS) and pro-
gression-free survival (PFS).
The median OS was 22.1 months (95% confidence
interval [CI], 17.7-not estimable) with cemiplimab
versus 14.3 months (95% CI, 11.7-19.2) with chemo-
therapy. The median PFS was 6.2 months (95% CI,
4.5-8.3) with cemip­limab versus 5.6 months (95% CI,
4.5-6.1) with chemotherapy. The overall response rate
was 37% (95% CI, 32%-42%) with cemiplimab and
21% (95% CI, 17%-25%) with chemotherapy.
The most common (≥10%) adverse reactions with
cemiplimab were musculoskeletal pain, rash, anemia,
fatigue, decreased appetite, pneumonia, and cough.
l Journal of Hematology Oncology Pharmacy 109