NCCN Guidelines for B-Cell Lymphomas V.1.

2021 – Annual – 09/22/20

Diagnosis
Guideline Page Institution Vote
Panel Discussion/References
and Request YES NO ABSTAIN ABSENT
DIAG-1 Based on a review of the data and discussion, the panel 0 27 0 4
External request did not use the language proposed in the submission.
Submission request from Adaptive However, the panel supported adding the following
Biotechnologies (09/01/20) language: “…(immunohistochemistry [IHC], flow cytometry,
a. Current language: PCR for IGHV molecular analysis to detect B-cell receptor
‘(immunohistochemistry, flow [BCR] and T-cell receptor [TCR] gene rearrangement,
cytometry, or PCR for IGHV karyotype, and or FISH for major translocations) may be
and TCR gene sufficient for diagnosis.”
rearrangements…)’.
i. We believe there may be a
small error here in that PCR
cannot be used for the • See Submission for references.
assessment of IGHV mutations,
but sequencing (NGS) can be
used.
b. Suggested language:
‘(immunohistochemistry, flow
cytometry, or PCR or NGS for
IGHV BCR and TCR gene
rearrangements, or NGS for
IGHV mutational
assessment…)’.
i. We attempted to clarify that
NGS or PCR can be used to
assess BCR/TCR gene
rearrangements while only
NGS can be used for IGHV
assessment.
NCCN Guidelines for B-Cell Lymphomas V.1.2021 – Annual – 09/22/20

Follicular Lymphoma (FOLL)

Guideline Page
and Request
FOLL-7 and FOLL-8
Internal request
Comment to consider the
removal of ibritumomab
tiuxetan as an option for 1)
histologic transformation of FL
to DLBCL (after minimal or no
prior therapies) with no
response or progressive
disease after
chemoimmunotherapy and 2)
as an option for histologic
transformation of FL to DLBCL
(after multiple lines of prior
therapies).
Institution Vote
Panel Discussion/References
YES NO ABSTAIN ABSENT
Based on the discussion, the panel consensus was to remove 27 0 0 4
ibritumomab tiuxetan as an option in the following settings due
to its limited clinical use:
• histologic transformation of FL to DLBCL (after minimal or
no prior therapies) for no response or progressive disease
after chemoimmunotherapy
• histologic transformation of FL to DLBCL (after multiple
lines of prior therapies)

FOLL-B and MZL-A Based on a review of the data and discussion, the panel 0 27 0 4
External request consensus did not support the inclusion of axicabtagene
Submission request from Kite ciloleucel as an option under second-line and subsequent
(09/18/20): Consider the therapy for follicular lymphoma (FOLL-B 2 OF 4) and second-
addition of axicabtagene line or subsequent therapy for marginal zone lymphomas
ciloleucel under second-line (MZL-A 2 OF 3) due to insufficient available data.
and subsequent therapy for
follicular lymphoma (FOLL-B 2
OF 4) and second-line or • See Submission for references.
subsequent therapy for
marginal zone lymphomas
(MZL-A 2 OF 3).
NCCN Guidelines for B-Cell Lymphomas V.1.2021 – Annual – 09/22/20
Marginal Zone Lymphoma (MZL)
Guideline Page
and Request
MZL-A
Internal request
Consider the inclusion of the
following footnote for second-
line and subsequent therapy of
marginal zone lymphomas:
Consider alternate BTKi
(acalabrutinib or zanubrutinib) in
patients with intolerance or
contraindications to ibrutinib.
Mantle Cell Lymphoma (MANT)
Guideline Page
and Request
MANT-A
Internal request
Comment to consider the
inclusion of “rituximab,
bendamustine followed by
rituximab, high-dose
cytarabine” as an induction
therapy (aggressive therapy)
for mantle cell lymphoma
(MCL).
MANT-A
Internal request
Comment to consider the
inclusion of “bendamustine +
rituximab + cytarabine
(RBAC500) (if not previously
given)” as a second-line and
subsequent therapy option for
MCL.
Institution Vote
Panel Discussion/References
YES NO ABSTAIN ABSENT
Based on the noted data and discussion, the panel
consensus supported the inclusion of following footnote for 27 0 0 4
second-line and subsequent therapy of marginal zone
lymphomas: “Consider alternate BTKi (acalabrutinib or
zanubrutinib) in patients with intolerance or contraindications
to ibrutinib.” These agents were added as a category 2A
recommendation.
Institution Vote
Panel Discussion/References YES NO ABSTAIN ABSENT
Based on a review of the noted data and discussion, the panel 27 0 0 4
consensus supported the inclusion of “rituximab, bendamustine
followed by rituximab, high-dose cytarabine” as an induction
therapy (aggressive therapy) for MCL. This is a category 2A,
preferred recommendation.
• Merryman R, Edwin N, Redd R, et al.
Rituximab/bendamustine and rituximab/cytarabine induction
therapy for transplant-eligible mantle cell lymphoma. Blood
Adv 2020;45:858-867.
Based on the noted data and discussion, the panel consensus 27 0 0 4
supported the inclusion of "bendamustine + rituximab +
cytarabine (RBAC500) (if not previously given)" as a second-
line and subsequent therapy option for MCL. This was added
as a category 2A, useful in certain circumstances
recommendation.
Visco C, Chiappella A, Nassi L, et al. Rituximab, bendamustine,
and low-dose cytarabine as induction therapy in elderly patients
NCCN Guidelines for B-Cell Lymphomas V.1.2021 – Annual – 09/22/20

with mantle cell lymphoma: a multicentre, phase 2 trial from

Fondazione Italiana Linfomi. Lancet Haematol 2017;4:e15-e23.
MANT-A Based on the discussion, the panel consensus supported the 27 0 0 4
Internal request inclusion of "± rituximab” to “venetoclax” as a second-line and
Comment to consider subsequent therapy option for MCL. This was added as a
changing “venetoclax” to category 2A, useful in certain circumstances recommendation.
"venetoclax ± rituximab" as a
second-line and subsequent
therapy option for MCL.
MANT-A Based on the discussion, the panel consensus supported the 27 0 0 4
Internal request change of “bendamustine ± rituximab (if not previously given)”
Comment to consider to “bendamustine + rituximab (if not previously given).” This is
changing “bendamustine ± as a category 2A, useful in certain circumstances
rituximab (if not previously recommendation.
given)” to “bendamustine +
rituximab (if not previously
given)" as a second-line and
subsequent therapy option.
MANT-A Based on the discussion, the panel consensus supported the
Internal request removal of following as second-line therapy options due to their 27 0 0 4
Comments to consider the limited clinical use:
removal of the following as • Bendamustine, bortezomib, and rituximab
second-line therapy options: • PEPC (prednisone, etoposide, procarbazine,
• Bendamustine, cyclophosphamide) ± rituximab
bortezomib, and rituximab • RCHOP
(category 2B) • VRCAP
• PEPC (prednisone, • Link to regimens on BCEL-C 2 of 5 for second-line therapy
etoposide, procarbazine, o ESHAP
cyclophosphamide) ± o GDP
rituximab (category 2B) o CEOP
• RCHOP or VRCAP (if not o ICE
previously given) (category o MINE
2B) o DAEPOC,
• Link to regimens on BCEL- o Gemcitabine + vinorelbine
C 2 of 5 for second-line
therapy

Diffuse Large B-Cell Lymphoma (DLBCL)

NCCN Guidelines for B-Cell Lymphomas V.1.2021 – Annual – 09/22/20

Guideline Page Institution Vote

and Request Panel Discussion/References YES NO ABSTAIN ABSENT
BCEL-B 1 of 3
Internal request The panel consensus supported the removal of dose-dense 27 0 0 4
Comment to consider the RCHOP-14 as a first-line therapy option for DLBCL due to
removal of dose-dense limited clinical use in this setting.
RCHOP-14 as an option for
DLBCL as a first-line therapy.

Primary Mediastinal Large B-Cell Lymphoma

Guideline Page Institution Vote
and Request Panel Discussion/References YES NO ABSTAIN ABSENT
BCEL-B 1 of 3
External request Based on the discussion, the panel consensus was to not
Submission request from include dosing recommendations for pembrolizumab. Dosing 0 27 0 4
Merck & Co., Inc. (05/29/20) recommendations are not included in the guidelines for other
for the inclusion of the regimens recommended for PMBL.
updated dosing
recommendations for • See Submission for references.
pembrolizumab, either 200
mg every 3 weeks or 400 mg
every 6 weeks administered
as a 30-minute intravenous
(IV) infusion until disease
progression, unacceptable
toxicity, or up to 24 months for
the treatment of adult patients
with primary mediastinal large
B-cell lymphoma (PMBL).

Castleman’s Disease
Guideline Page Institution Vote
and Request Panel Discussion/References YES NO ABSTAIN ABSENT
CD-3 Based on the discussion of data in the provided references 27 0 0 4
External request the panel consensus supported the removal of the qualifying
Submission request from language, “for plasmacytic/mixed histology” and
NCCN Guidelines for B-Cell Lymphomas V.1.2021 – Annual – 09/22/20

Castleman Disease corresponding footnote “Patients with hyaline vascular

Collaborative Network’s (CDCN) histology do not benefit from siltuximab.”
Scientific Advisory
Board, (09/08/20): Insufficient • See Submission for references.
evidence exists to use
histopathologic subtype to guide
treatment of iMCD. Therefore,
we strongly suggest that
histopathological subtype should
not be used to guide treatment
decisions of iMCD and that
siltuximab should be
recommended first line for all
iMCD patients regardless of
histopathological subtype
assigned (changed from the
current NCCN recommendation
against its use for patients
categorized as having hyaline
vascular histopathology; see
page CD-3, preferred iMCD
treatment, footnote p).
CD-3 Based on the discussion of data in the provided references 27 0 0 4
Internal request the panel consensus supported the removal of the qualifying
Comment to consider the language, “hyaline vascular histology” from primary treatment
removal of qualifier, option, thalidomide, cyclophosphamide, prednisone.
“hyaline vascular histology” from
primary treatment option, See Submission for references.
thalidomide, cyclophosphamide,
prednisone.

Principles of Radiation Therapy

Guideline Page Institution Vote
and Request Panel Discussion/References YES NO ABSTAIN ABSENT
NHODG-D 3 of 4 The panel consensus was to include, “4 Gy in 2 fractions may 27 0 0 4
External request be considered in select patients (ie, the elderly or patients
with Sjogren syndrome) for whom the increased risk of late
NCCN Guidelines for B-Cell Lymphomas V.1.2021 – Annual – 09/22/20

Submission request from orbital toxicity outweighs the documented efficacy of definitive
Oncology Analytics Inc, dose schedules (24 Gy).”
(02/08/20): Under “Definitive
treatment (1.5-2.0 Gy daily • See Submission for references.
fractions),” please include “2 Gy
x 2 fractions” as an option for
orbital FL, MZL and early-stage
MCL. Currently, the NCCN
Guidelines recommend definitive
treatment with “24-30 Gy” for FL
and MZL and “24-36 Gy” for
early-stage MCL, with no
anatomic site specified for the
dose recommendations. The
NCCN Guidelines only
recommend the use of 2 Gy x 2
fractions for FL/MZL/MCL/SLL
under “Palliative RT.”

Special Considerations for the Use of Small Molecule Inhibitors

Guideline Page Institution Vote
and Request Panel Discussion/References YES NO ABSTAIN ABSENT
NCCN Guidelines for B-Cell Lymphomas V.1.2021 – Annual – 09/22/20

NHODG-D 3 of 4 Based on the discussion of data in the provided references, 27 0 0 4

External request the panel consensus was to include infection prophylaxis for
Submission request from other BTK inhibitors: acalabrutinib and ibrutinib.
BeiGene, Ltd., (04/17/20):
(1) The addition to the • See Submission for references.
Guidelines of the rates of
infection and the need to
consider prophylaxis for all three
BTK inhibitors, for parity in risk
communication across the class.
OR
(2) The removal of the following
information from the
zanubrutinib listing under
Special Considerations for the
Use of Small Molecule Inhibitors
(NHODG-E): Infections: Grade
3 or higher infections occurred in
23% of patients treated with
zanubrutinib monotherapy.
Consider prophylaxis for herpes
simplex virus, PJP, and other
infections according to standard
of care in patients who are at
increased risk for infections.