R-CHOP, either with or without autoSCT. This
study found that in patients younger than 65,
R-CHOP followed by autoSCT or R-hyper-CVAD
without autoSCT resulted in similar PF and OS,
but was superior to R-CHOP alone for newly diagnosed MCL patients. 35 These data support more
intensive regimens in younger and fitter patients.
Several other prospective and randomized studies
have demonstrated clinical benefit for patients
with MCL undergoing autoSCT in first remission.
Of particular importance is the seminal phase
3 study of the European MCL Network, which
established the role of autoSCT in this setting.61
In this prospective randomized trial involving 122
newly diagnosed MCL patients who responded
to CHOP-like induction, patients in CR derived a
greater benefit from autoSCT.
More recent studies have demonstrated similar benefits using cytarabine-based autoSCT. The
Nordic MCL2 study evaluated 160 patients using
R-CHOP, alternating with rituximab and high-dose cytarabine, followed by autoSCT. This study
used “maxi-CHOP,” an augmented CHOP regimen (cyclophosphamide 1200 mg/m2, doxorubicin 75 mg/m2, but standard doses of vincristine
[ 2 mg] and prednisone [100 mg days 1–5]), alternating with 4 infusions of cytarabine at 2 g/m2
and standard doses of rituximab (375 mg/m2).
Patients then received conditioning with BEAM
and autoSCT. Patients were evaluated for the
presence of minimal residual disease (MRD)
and for the t( 11; 14) or clonal immunoglobulin
heavy chain gene rearrangement with poly-merase chain reaction (PCR). Patients with
MRD were offered therapy with rituximab at
375 mg/m2 weekly for 4 doses. This combination resulted in 10-year OS rates of 58%. 36 In
a multicenter study involving 78 patients from
the Cancer and Leukemia Group B (CALGB),
R-CHOP followed by high-dose cytarabine
and BEAM-based autoSCT resulted in a 5-year
OS of 64%. 37 A single-arm phase 2 study from
the Netherlands also tested R-CHOP followed
by high-dose cytarabine and BEAM-based
autoSCT. Nonhematologic toxicities were 22%
after high-dose cytarabine, and 55% after
BEAM. The ORR was 70%, with a 64% CR rate
and 66% OS at 4 years. 38 The French GELA
group used 3 cycles of R-CHOP and 3 cycles of
R-DHAP in a phase 2 study of young (under age
66) MCL patients. Following R-CHOP, the ORR
was 93%, and following R-DHAP the ORR was
95%. Five-year OSA was 75%. 39 A large randomized phase 3 study by Hermine and colleagues
of the EMCLN confirmed the benefit of this
approach in 497 patients with newly diagnosed
MCL. R-CHOP for 6 cycles followed by autoSCT
was compared to R-CHOP for 3 cycles alternating with R-DHAP for 3 cycles and autoSCT with a
cytarabine-based conditioning regimen. The addition of cytarabine significantly increased rates
of CR, TTF, and OS, without increasing toxicity. 40
CASE CONTINUED
The patient is treated with R-CHOP chemotherapy for 3 cycles followed by R-DHAP.
His course is complicated by mild tinnitus and
acute kidney injury from cisplatin that promptly
resolves. Three weeks following treatment, a
restaging PET/CT scan shows resolution of
all lymphadenopathy, with no hypermetabolic
uptake, consistent with a complete remission.
A repeat bone marrow biopsy shows no involvement with MCL. He subsequently undergoes
an autoSCT, and restaging CT/PET 3 months
following autoSCT shows continued remission.
He is monitored every 3 to 6 months over the
next several years.
He has a 4.5-year disease remission, after
which he develops growing palpable lymphadenopathy on exam and progressive anemia
and thrombocytopenia. A bone marrow biopsy is repeated, which shows recurrent MCL.
Restaging diagnostic imaging with a CT scan
reveals lymphadenopathy above and below the
diaphragm. An axillary lymph node biopsy also
demonstrates recurrent MCL. At this time the
patient is otherwise in fairly good health, except
for feeling fatigued. His ECOG performance
status is 1. He begins therapy with bortezomib
