original articles
Annals of Oncology
Annals of Oncology 24: 2887–2892, 2013
doi:10.1093/annonc/mdt271
Published online 16 July 2013
Modified cisplatin, etoposide, and ifosfamide (PEI)
salvage therapy for male germ cell tumors: long-term
efficacy and safety outcomes†
A. Necchi1, N. Nicolai2, L. Mariani3, D. Raggi1, E. Farè1, P. Giannatempo1, M. Catanzaro2,
D. Biasoni2, T. Torelli2, S. Stagni2, A. Milani2, L. Piva2, G. Pizzocaro4, A. M. Gianni1,5 & R. Salvioni2
Departments of 1Medical Oncology; 2Surgery, Urology Unit; 3Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan;
4
Urology Unit, San Giuseppe Hospital, Milan; 5University of Milan School of Medicine, Milan, Italy
Received 23 February 2013; revised 8 May 2013; accepted 3 June 2013
Background: Since 1985, we introduced a modified combination of etoposide, ifosfamide, and cisplatin (PEI) as
second-line therapy of adult male germ cell tumors with the aim to reduce toxic effect while maintaining efficacy over
the original regimen.
Patients and Methods: Patients received four cycles of ifosfamide at 2.5 g/m2 on days 1–2, etoposide, and cisplatin
at 100 and 33 mg/m2, respectively, on days 3–5 every 21 days, followed by surgery. Results were stratified according to
the International Germ Cell Consensus Classification Group-2 (IGCCCG-2).
Results: From February 1985 to January 2012, 189 patients were treated. 72.6% were IGCCCG-2 intermediate-to-very
high risk. Thirty-five patients (18.5%) had a complete response, 67 (35.4%) a marker normalization (PRm−). Median
follow-up was 122.1 months (inter-quartile range [IQR]: 71.4–232.0). Two-year progression-free and 5-year overall
survival were 34.3% [95% confidence interval (CI) 28.1% to 41.9%] and 42.1% (95% CI 35.3% to 50.2%), respectively.
Survival estimates compared favorably with those obtained by conventional dose chemotherapy (CDCT) regimens in
each prognostic category. 70.4% of grade 3–4 neutropenia (25.5% febrile neutropenia), 48.1% thrombocytopenia,
21.2% anemia, 3.2% neurotoxic effect, and no severe renal toxic effect were recorded.
Conclusion: Dose-modified Italian PEI should be considered as an appropriate benchmark for CDCT in the first salvage
setting.
Key words: combination chemotherapy, salvage therapies, testicular neoplasms
introduction
First-salvage chemotherapy for relapsing or progressing male
germ cell tumors (GCT) is a debated issue as neither a standard
regimen nor a superior strategy between conventional dose
(CDCT) and high-dose chemotherapy (HDCT) was definitely
established. Since the early 1990s, available options for secondline attempt are constituted by the combination of cisplatin and
ifosfamide with either etoposide (VIP) or vinblastine (VeIP)
[1–7]. Results of these regimens are obtained from long-dated
series consisting of small number of patients and comparing
across studies is fraught with difficulty, either when focusing on
efficacy outcomes or even more when dealing with safety and
toxic effect. Taken together, regimens conventionally used in the
Correspondence to: Dr Andrea Necchi, Department of Medical Oncology, Medical
Oncology 2 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1,
20133 Milano, Italy. Tel: +39-02-2390-2402; Fax: +39-02-2390-3150;
E-mail: [email protected]
†
Presented at the 2013 Genitourinary Cancers Symposium, Conquer Cancer Foundation
of ASCO Merit Award recipient, 14–16 February 2013, Orlando, FL, USA.
pre-taxane era resulted in a complete response (CR) rate in the
range of 35%–50% and a maintained CR-rate approximating
20%–25%. Very promising results were further reported with
the introduction of paclitaxel in combination with ifosfamide
and cisplatin (TIP) in a selected population of 46 patients with
good clinical features as 70% of CR were obtained, 65% of
patients being progression-free at 2 years [8]. In the second half
of the 1980s, we treated a pilot cohort of 36 consecutive male
patients with a modified VIP regimen with the aim to reduce
toxic effect while preserving activity over the original regimen.
Ifosfamide was given at a reduced dose (2.5 g/m2) the first
2 days followed by a slightly reduced total dose of etoposide
(100 mg/m2) combined with a slightly increased dose of
cisplatin (40 mg/m2) given for the remaining three days.
Substitution of etoposide with vinblastine (PVI) at the dose of
6 mg/m2 was provided in this series to patients pretreated with
cisplatin, etoposide, and bleomycin (PEB). Overall side-effects
were moderate and a maintained remission rate of 42% was
obtained, that improved to 70% for those who had responded to
primary chemotherapy, at a long-term follow-up [9]. PVI was
© The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: [email protected].
original articles
abandoned after the first eight patients due to poor activity. We
then further modified VIP combination by reducing the dose of
cisplatin as described below and since then this regimen, called
PEI combination, was actually introduced as the second-line
therapy at Fondazione IRCCS Istituto Nazionale dei Tumori,
Milan.
materials and methods
Since 1985, PEI chemotherapy was administered in all consecutive
patients failing first-line regimen consisting of at least three cycles of the
combination of cisplatin and bleomycin plus either etoposide (PEB) or
vinblastine (PVB), followed by surgery in all eligible cases. Regimen
consisted of the administration of ifosfamide at the dose of 2.5 g/m2 on
days 1 and 2 (with intravenous mesna protection at 600 mg/m2 q6 h days
1,2) followed by cisplatin at 33 mg/m2 and etoposide at 100 mg/m2 both
on days 3–5. Granulocyte- or granulocyte-macrophage colony-stimulating
factor (G-CSF or GM-CSF) were administered following chemotherapy in
case of grade 3–4 neutropenia up to November 2008. Since then,
prophylactic use of pegylated G-CSF (Peg-GCSF) was administered on
day 6 of each cycle as a standard policy. Program provided four cycles of
PEI every 3 weeks, followed by surgery in all responding cases with
resectable disease. Baseline assessments included serum tumor markers
[STM, alpha-fetoprotein (AFP), beta-human choriogonadotropin (HCG),
and lactate dehydrogenase], and a total body computed tomography scan,
to be repeated before each cycle (STM), and after two cycles and at the
end of treatment (radiologic restaging). A CR was defined as a complete
disappearance of all clinical, radiographic, and biochemical evidence of
disease for a minimum of 4 weeks. A partial response with negative
markers (PRm−) was defined as a normalization of tumor markers
without surgery of residuals while a PR-positive markers (PRm+) was
defined as an incomplete marker negativization in patients without a
surgical procedure for a residual mass. PRm− patients undergoing
surgery were further categorized as having fibrosis and necrosis, viable
residual tumor, or teratoma. Stable disease (SD) was defined in all cases
which were not deemed to be judged as response nor as disease
progression. Patients who achieved a CR, PR, or SD were not considered
to have had an event in the progression-free survival (PFS) analysis until
they developed evidence of disease progression, defined by rising STM,
increasing size of nonteratomatous tumor masses or development of new
tumor masses.
Disease was considered cisplatin refractory when at least tumor
stabilization or a remission had been achieved, but tumor progression
occurred again within four weeks of the last cisplatin administration.
Disease progressing under chemotherapy was defined as absolutely
refractory. Side-effects were graded according to the updating versions of the
National Cancer Institute–Common Terminology Criteria for Adverse
Events (NCI-CTCAE) [10].
statistical analysis
Tumor response to treatment was assessed according to the intent-totreat principle and two patients with missing information were
considered as failures. Exact 95% confidence interval (CI) of response
proportion was calculated based on the binomial distribution.
Event times were calculated starting from the date of PEI chemotherapy
initiation up to the date of event occurrence, and censored at the date of last
contact for event-free patients. For each end point, survival curves were
obtained with the Kaplan–Meier method considering the overall series or
with stratification for the International Germ Cell Consensus Classification
Group-2 (IGCCCG-2) risk score [11], and the log-rank test was used for
 | Necchi et al.
Annals of Oncology
comparison across different risk categories. A Cochran–Armitage test
for trend was used to assess the association between response rate (CR and
PRm−) and IGCCCG-2 risk category. Multivariable analysis based on Cox
regression models was also undertaken to evaluate the prognostic effect
of the following prespecified factors: tumor primary site, Memorial
Sloan–Kettering Cancer Center (MSKCC) risk category (good versus poor)
[8, 12], IGCCCG prognostic category [13], IGCCCG-2, late relapse, presence
of liver, bone, or brain (LBB) metastases, value of elevated markers at
relapse, and response to first-line therapy (CR or PRm− versus incomplete
response). Because of the strong correlation between IGCCCG and
IGCCCG–2, these two factors were alternatively entered into the Cox
models.
The analyses were carried out using the SAS® and R software (http://www.
r-project.org/, last access 20 December 2012), and the results were
considered statistically significant whenever a two-sided P-value below 5%
was achieved.
results
From February 1985 to January 2012, 189 consecutive patients
were treated after failure of either PVB (N = 25) or PEB
(N = 164). Table 1 presents their principal characteristics;
briefly, median age was 30 years (IQR: 25–35), 31 of them
(16.7%) were late relapses, 13 (6.9%) had a primary mediastinal
GCT, and 72.6% of them presented with IGCCCG-2
intermediate-to-very high-risk score, 41 (21.7%) had LBB
metastases, and 28 (14.8%) had a cisplatin resistant disease
(e.g. had a refractory or absolutely refractory disease). Median
number of administered cycles was 4 (IQR: 3.4) and no
permanent discontinuations due to toxic effect were observed.
Eighty-one patients (42.9%) had a dose reduction of one drug
(N = 47) or more (N = 34) for at least one cycle, 78% of them
being treated before 2000. Most frequent reduction consisted of
the administration of ifosfamide at the 75%–80% of total dose,
either alone (N = 41) or with concomitant reduction to 75%
cisplatin (N = 11). CR to chemotherapy was achieved in 35
patients (18.5%; 95% CI 13.3% to 24.8%) while 67 patients
(35.4%; 95% CI 28.6% to 42.7%) obtained a PRm−, 41 of them
being radically resected. Therefore, the resulting total diseasefree (NED) rate after chemotherapy plus surgery was 40.2%
(95% CI 33.2% to 47.6%, Table 2). Fourteen patients (7.4%)
yielded neither evidence of residual disease nor teratoma in the
resected tissue. Responses ranged between 23.5% in the very
high-risk category to 72.7% in the very low-risk one (P < 0.001).
Median follow-up was 122.1 months (IQR: 71.4–232.0).
A total of 133 progressions and 114 deaths were recorded.
Median PFS was 7.2 months (95% CI 6.2–9.5) while 2-year PFS
was 34.3% (95% CI 28.1% to 41.9%). Median survival was
21.7 months (95% CI 16.7–69.5) while 5-year overall survival
(OS) was 42.1% (95% CI 35.3% to 50.2%) (Table 3 and
Figure 1A and B). Two-year PFS ranged from 63.6%
(95% CI 40.7% to 99.5%) in the very low-risk category to 5.5%
(95% CI 0.8% to 37.3%) in the very high-risk one while five-year
OS ranged 72.7% (95% CI 50.6% to 100.0%) to 5.6% (95% CI
0.8% to 37.3%). Differences across IGCCCG-2 categories were
statistically significant (P < 0.001) (Table 3, Figure 1C and D).
At multivariable analysis (MVA) extragonadal primary
(HR: 2.53, 95% CI 1.44–4.44), presence of LBB metastases (HR:
1.68, 95% CI 1.09–2.57), and HCG >1000 mIU/ml (HR: 1.70,
Volume 24 | No. 11 | November 2013
original articles
Annals of Oncology
Table 1. Patient characteristics at baseline
Table 2. Results with PEI chemotherapy (N = 189a)
Characteristic
No. of patients
Total no. of patients
Age: median (IQR), years
Time frame
Late relapse
Tumor primary
Gonadal
Mediastinal
Extragonadal
IGCCCG category
Good
Intermediate
Poor
Not assessable
IGCCCG-2 category
Very low risk
Low risk
Intermediate risk
High risk
Very high risk
Not assessable
Platinum sensitivity
Sensitive
Refractory
Absolutely refractory
Not assessable
LBB metastases
First-line regimen
PEB
PVB
Markers pre-PEI
AFP > 1000 IU/ml
HCG > 1000 IU/l
Disease sites pre-PEI
Retroperitoneum
Lung
Liver
Mediastinum
Brain
Bone
Markers only
No. of metastatic sites pre-PEI
0–1
2
>2
189
30 (25–35)
February 1985–January 2012
31
%
16.7
166
13
10
87.8
6.9
5.3
103
32
44
10
54.5
17.0
23.2
5.3
11
36
93
26
18
5
5.8
19.0
49.2
13.8
9.6
2.6
157
22
6
4
41
83.1
11.6
3.2
2.1
21.7
164
25
86.8
13.2
18
20
9.5
10.6
102
83
24
48
11
11
5
53.9
43.9
12.7
25.4
5.8
5.8
2.6
112
51
26
59.2
27.0
13.8
–
AFP, Alpha-Fetoprotein; CDDP, cisplatin; HCG, Human Chorionic
Gonadotropin; IGCCCG, International Germ Cell Consensus Classification
Group; IQR, inter-quartile range; IU, International Unit; LBB, Liver, Bone,
and Brain metastases; PEB, cysplatin, etoposide, and bleomycin; PEI,
cisplatin, etoposide, and ifosfamide; PVB, cisplatin, vinblastine, and
bleomycin.
95% CI 1.02–2.86) were significant for PFS while tumor
primary (HR: 3.06, 95% CI 1.68–5.58), LBB metastases (HR:
2.02, 95% CI 1.30–3.16), and AFP > 1000 IU/ml (HR: 2.78, 95%
CI 1.51–5.14) were in relation to OS (Supplementary Table S1,
available at Annals of Oncology online). No treatment-related
deaths were observed, grade 3–4 hematologic toxic effect was
Volume 24 | No. 11 | November 2013
Response
No. of patients
%
CR to chemotherapy alone
PRm−
PRm− radically resected
Fibrosis and necrosis
Viable cancer
Teratoma
Total NED rate after treatment
Incomplete response (PRm+/SD)
Disease progression
35
67
41
14
14
13
76
46
39
18.5
35.4
21.6
7.4
7.4
6.8
40.2
24.3
20.6
CR, complete response; NED, disease-free; PEI, cisplatin, etoposide, and
ifosfamide; PRm−, partial response with normal/normalized markers;
PRm+, partial response with markers still elevated; SD, stable disease.
a
Two patients were not assessable for response.
seen in 133 patients (70.4%) who developed neutropenia (25.5%
febrile neutropenia), 40 patients (21.2%) anemia, and 91
(48.1%) thrombocytopenia. Nonhematologic toxic effect was
mild, as there were no severe renal side-effects, the rate of severe
neurotoxicity (including ototoxicity) as well as of
gastrointestinal toxic effect was <5% (Supplementary Table S2,
available at Annals of Oncology online).
discussion
To the best of our knowledge, this is the largest series relative to
a single-salvage chemotherapy regimen for patients with GCT,
including HDCT experiences. Despite the shortcomings
attributable to the long-dated series and the retrospective
quality, results should be viewed in the light of continuing
improvements of supportive care and the use of myeloid growth
factors, and one may argue that the side-effect rate, as well as the
yet relatively high dose intensity we achieved, might be further
improved in the prospective population.
Retrospective bias may particularly reflect on toxic effect
reporting as side-effects were not uniformly and thoroughly
evaluated outside of a clinical trial setting. This may result in
underestimating events and under-representing extrahematologic toxic effect, and this is the reason why we
reported on the severe side-effects only. Of note, reduction in
dose of ifosfamide and etoposide compared with the original
schedules determined a very low rate of febrile neutropenia
and extra-hematologic toxic effect, particularly regarding
neurologic and renal side-effects. A comparison of side-effects
across different regimens is very hard and perhaps the
benchmark is provided by the standard-dose arm (VIP/VeIP)
of the IT-94 trial [14]. In the 136 patients of the latter, an
overall rate of 88.2% and 55.6% of severe neutropenia and
thrombocytopenia, respectively and 49.3% of febrile
neutropenia were reported, far beyond what we reported with
PEI through the years. Moreover, four toxic deaths were
observed in this arm.
As for the efficacy results achievable with CDCT in the pure
second line, the options currently available and based on large
series are relative to VeIP chemotherapy on 135 patients, and
the standard-dose arm regimen of the IT-94 trial on 136
doi:10.1093/annonc/mdt271 | 
original articles
Annals of Oncology
Table 3. Survival according to IGCCCG-2 risk score in patients treated with PEI chemotherapy
Prognostic group of
treatment
Progression-free survival
No. of
Median PFS
events
(months)
2-year PFS
(%)
95% CI
(%)
P**
All patients
Very low risk
Low risk
Intermediate risk
High risk
Very high risk
133
5
23
67
21
17
34.3
63.6
38.7
37.8
23.1
5.5
28.1–41.9
40.7–99.5
25.6–58.5
29.2–48.9
11.4–46.6
0.8–37.3
<0.001 114
4
19
58
16
17
7.2
>43.2
10.8
7.9
4.5
3.55
Overall survival
No. of
Median OS
events
(months)
21.7
>86.4
79.6
28.5
13.3
8.4
5-year OS
(%)
95% CI
(%)
P
42.1
72.7
56.1
41.9
34.0
5.6
35.3–50.2
50.6–100
41.6–75.6
32.7–53.8
18.9–61.0
0.8–37.3
<0.001
CI, confidence interval; IGCCCG-2, International Germ Cell Consensus Classification Group-2; OS, overall survival; PEI, cisplatin, etoposide, ifosfamide;
PFS, progression-free survival; **P, Log-rank test P-value.
Figure 1. Kaplan–Meier curves of progression-free and overall survival in the entire set (A and B) and in each of the five prognostic categories according to
IGCCCG-2 score (C and D). IGCCCG-2, International Germ Cell Consensus Classification Group-2.
patients. Additional published reports using VIP/VeIP are based
on limited number of patients: 48 (1986) [2], 40 (1990) [5],
30 (1991) [3], 54 (1996) [6], and 56 (1997) [7]. Since the
introduction of a paclitaxel-containing regimen (TIP) in recent
 | Necchi et al.
years, this was felt as the most suitable option for patients not
cured by PEB but, again, information available is relative to
46 patients only and with good prognostic features as they were
selected among those with favorable prognosis according to
Volume 24 | No. 11 | November 2013
original articles
Annals of Oncology
MSKCC [8]. Of note, a multicenter British Medical Research
Council-sponsored trial using a modified TIP schedule with a
slight reduction in paclitaxel total dose mirrored the results of
the pre-taxane era in an unselected patient population [15]. In
the last years, the renaissance of the salvage HDCT approach
basically entailing the administration of a double course of highdose carboplatin and etoposide or three-courses of the same
combination preceded by an induction with two cycles of
paclitaxel and ifosfamide (TI-CE) raised the need for a
reassessment of the first-salvage strategy [16, 17]. Actually, up to
70% of second-line and 50% of multirelapsing/refractory
patients benefited from durable responses in Einhorn’s series
while 5-year PFS and OS with TI-CE were 48 and 52%,
respectively. The major pitfall when considering possible
implications of the use of HDCT in an earlier disease setting
(e.g. the first-salvage attempt) is the lacking evidence of
superiority coming from a randomized trial. Yet, the only
randomized trial comparing four cycles of VIP/VeIP to
three cycles of the same chemotherapy followed by one
HDCT course with carboplatin, etoposide, and
cyclophosphamide (CarboPEC) failed to meet the primary
efficacy end point [14].
The availability of new prognostic categories (very low risk,
low risk, intermediate risk, high risk, and very high risk) in
the second-line setting currently allows a more reliable
comparison and stratification of results not only between the
two treatment modalities but also within each one of them.
For our purposes, the benchmark for CDCT was taken from
the retrospective international comparison of conventional
dose versus HDCT including a multiplicity of regimens [18].
Survival estimates in terms of 2-year PFS and 5-year OS in
the different prognostic categories are open to discussion. Of
note, efficacy with PEI compares favorably with that reported
in almost all IGCCCG-2 risk categories: in particular, 2-year
PFS with PEI is of 23.1% and 5.5% in the high- to very highrisk categories compared with 17.2% and 1.9%, while 5-year
OS is 34.0% and 5.6% versus 23.0% and 3.4%, respectively. In
the category of high-risk patients, results are comparable with
those reported with the use of a HDCT strategy. Looking
again at the IT-94 cohort, a similar rate of CR was achieved
(23% versus 18.5% with PEI) but a lower rate of PRm− (17%
versus 35.4% with PEI) with comparable survival
outcomes. Unfortunately, a categorization of results
according to IGCCCG-2 score is not available in Einhorn’s
and TI-CE series.
Taken together, these results confirmed the good premises we
achieved in the pilot population of patients and lended support
to the rationale of modifying the original VIP schedule in order
to improve tolerability while preserving (or perhaps improving)
efficacy. Interestingly, despite we initially reported poorer results
in the cohort of patients who were cisplatin refractory, efficacy
in the present series seems to be maintained even in the
categories of patients at higher risk. At MVA, the presence of
LBB metastases confirmed as one of the most negative
prognostic factors of either PFS or OS. Moreover, a trend toward
a poorer prognosis was observed for patients presenting with
high levels of AFP (95% CI levels at the limit of significance for
PFS and a hazard ratio of 2.78 for OS, with a 95% CI value of
5.14 at the upper bound).
Volume 24 | No. 11 | November 2013
It is commonly perceived that, in the absence of a
randomized comparison, it will be impossible to drive a
roadmap for the first-salvage setting. If tandem or triple courses
of high-dose carboplatin and etoposide seem recommended
options, the excellent tolerability and good efficacy of the
modified PEI regimen described here prompt its use as a
convenient alternative to similarly effective, yet more toxic
salvage regimens. Consistency of results in relation to the
sample size provides a compelling argument for a randomized
comparison with either a CDCT regimen or HDCT.
funding
This work was not supported by any grant funding.
disclosure
The authors have declared no conflicts of interest.
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L. Zhang8, K. Prandi8, J. Li8 & T. E. Witzig9*
1
Institute of Hematology ‘Seràgnoli’, University of Bologna, Bologna, Italy; 2Section of Hematology/Oncology, Nebraska Medical Center, Omaha, USA; 3Department of
Medicine, Lymphoma/Myeloma Service, Roswell Park Cancer Institute, Buffalo, USA; 4Department of Medicine, Division of Hematology, Mayo Clinic Arizona, Scottsdale,
USA; 5Lymphoid Blood Diseases Unit, Hôpital Henri Mondor, Créteil, France; 6Department of Hematology/Oncology, Southern California Kaiser Permanente, San Diego,
USA; 7Hematology Service, Centre Henri Becquerel, Rouen, France; 8Celgene Corporation, Summit, USA; 9Department of Medicine, Division of Hematology, Mayo Clinic,
Rochester, USA
Received 6 February 2013; revised 20 July 2013; accepted 23 July 2013
Background: Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin lymphoma with poor overall
prognosis, requiring the development of new therapies. Lenalidomide is an immunomodulatory agent demonstrating
antitumor and antiproliferative effects in MCL. We report results from a long-term subset analysis of 57 patients with
relapsed/refractory MCL from the NHL-003 phase II multicenter study of single-agent lenalidomide in patients with
aggressive lymphoma
Design: Lenalidomide was administered orally 25 mg daily on days 1–21 every 28 days until progressive disease (PD) or
intolerability. The primary end point was overall response rate (ORR).
Results: Fifty-seven patients with relapsed/refractory, advanced-stage MCL had a median of three prior therapies. The
ORR was 35% [complete response (CR)/CR unconfirmed (CRu) 12%], with a median duration of response (DOR) of
16.3 months (not yet reached in patients with CR/CRu) by blinded independent central review. The median time to first
response was 1.9 months. Median progression-free survival was 8.8 months, and overall survival had not yet been
reached. The most common grade 3/4 adverse events (AEs) were neutropenia (46%), thrombocytopenia (30%), and
anemia (13%).
Conclusions: These results show the activity of lenalidomide in heavily pretreated, relapsed/refractory MCL.
Responders had a durable response with manageable side-effects. Clinical trial number posted on www.clinicaltrials.gov
NCT00413036.
Key words: lenalidomide, mantle cell lymphoma, non-Hodgkin lymphoma
introduction
Mantle cell lymphoma (MCL) is an uncommon type of nonHodgkin lymphoma (NHL) comprising <10% of all newly
diagnosed patients [1, 2]. Classified as an aggressive NHL
*Correspondence to: Dr Thomas E. Witzig, Department of Medicine, Division of
Hematology, Mayo Clinic, Stabile 628, 200 First Street, SW, Rochester, MN 55905-0002,
USA. Tel: +1-507-266-2040; Fax: +1-507-266-9277; E-mail: [email protected]
subtype, MCL has the worst prognosis of B-cell subtypes owing
to its aggressive clinical disease course and incurability with
standard chemotherapy. Conventional first-line therapy for
bulky or advanced disease primarily consists of chemotherapy
combined with rituximab, with possible consolidation with
autologous stem cell transplantation (ASCT) for younger
patients in remission to improve overall patient outcomes.
However, options for relapsed MCL are limited although several
© The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an Open Access article distributed under the
terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution,
and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]