differences were observed among groups. This
study underscores that deferred treatment can
be an acceptable alternative in selected MCL patients for a short period of time. In practice, the
type of patient who would be appropriate for
this approach is someone who is frail, elderly,
and with multiple comorbidities. Additionally,
expectant observation could be considered for
patients with limited-stage or low-volume MCL,
low Ki-67 index, and low-risk MIPI scores.
Approach to Therapy
Treatment of MCL is generally approached
by evaluating patient age and fitness for treatment. While there is no accepted standard, for
younger patients healthy enough to tolerate aggressive approaches, treatment often involves an
intensive cytarabine-containing regimen, which
is consolidated with an autoSCT. This approach
results in the longest remission duration, with
some series suggesting a plateau in survival after
5 years, with no relapses. 21 Nonintensive conventional chemotherapy alone is often reserved for
the frailer or older patient. Given that remission
durations with chemotherapy alone in MCL are
short, goals of treatment focus on maximizing
benefit and remission duration and minimizing
risk of toxicity.
Standard Chemotherapy: Elderly and/or Frail
Patients
Conventional chemotherapy alone for the
treatment of MCL results in a 70% to 85% over-
all response rate (ORR) and 7% to 30% com-
plete response (CR) rate. 22 Rituximab, a mouse
humanized monoclonal IgG1 anti-CD20 anti-
body, is used as standard of care in combination
with chemotherapy, since its addition has been
found to increase response rates and extend
both progression-free survival (PFS) and OS
compared to chemotherapy alone. 23, 24 However,
chemoimmunotherapy approaches do not pro-
vide long-term control of MCL and are consid-
ered noncurative. Various regimens have been
studied and include anthracycline-containing
regimens such as R-CHOP (rituximab with
cyclophosphamide, doxorubicin, vincristine,
prednisone), 22 combination chemotherapy with
antimetabolites such as R-hyper-CVAD (hyper-
fractionated rituximab with cyclophosphamide,
vincristine, doxorubicin, dexamethasone, al-
ternating with methotrexate and cytarabine), 25
purine analogue–based regimens such as R-FC
(rituximab with fludarabine and cyclophospha-
mide), 26 bortezomib-containing regimens, 27 and
alkylator-based treatment with BR (bendamus-
tine and rituximab) (Table 1). 28, 29 Among these,
the most commonly used are R-CHOP and BR.
Two large randomized studies compared
R-CHOP for 6 cycles to BR for 6 cycles in patients
with indolent NHL and MCL. Among MCL
patients, BR resulted in superior PFS compared
to R-CHOP (69 months versus 26 months) but
no benefit in OS. 28, 29 The ORR to R-CHOP was
approximately 90%, with a PFS of 21 months in
the Rummel et al study. 29 This study included
more than 80 centers in Germany and enrolled
549 patients with MCL, follicular lymphoma,
Table 1. Commonly Used Standard First-line Chemotherapy Approaches for Mantle Cell Lymphoma
Regimen ORR/CR PFS OS Reference
R-CHOP 91% Median PFS 21 mo NA Rummel et al29
R-CHOP + maintenance rituximab 86% Median PFS 4 yr 4-yr OS 87% Kluin-Nelemans et al26
R-CHOP + bortezomib 91% 2-yr PFS 44% 2-yr OS 86% Ruan et al31
Bendamustine + rituximab 93% Median PFS 35 mo NA Rummel et al29
97% NA NA Flinn et al28
CR = complete response; NA = not available; ORR = overall response rate; OS = overall survival; PFS = progression-free survival; R-CHOP = rituximab
with cyclophosphamide, doxorubicin, vincristine, prednisone.
