European Journal of Haematology 93 (18)

REVIEW ARTICLE

Antibodies and antibody-drug conjugates in the treatment of

Hodgkin lymphoma
Dennis A. Eichenauer1,2, Andreas Engert1,2
1

First Department of Internal Medicine, University Hospital Cologne, Cologne; 2German Hodgkin Study Group (GHSG), Cologne, Germany

Abstract
Hodgkin lymphoma (HL) is a B cell-derived lymphoid malignancy most often affecting young adults. More
than 80% of HL patients achieve long-term remission after appropriate first-line treatment consisting of
multiagent chemotherapy and/or radiotherapy (RT). In addition, approximately 50% of patients with disease
recurrence remain relapse-free after salvage therapy with high-dose chemotherapy followed by autologous
stem cell transplantation (ASCT). However, patients with multiple relapses are mostly in a palliative
situation, and novel drugs for this patient group are needed. Furthermore, novel less toxic but equally
effective first-line and second-line approaches are required as therapy-related late sequelae represent a
relevant cause of morbidity and mortality in HL survivors. Several antibodies and antibody-drug conjugates
(ADC) targeting CD30 and CD20 have recently been evaluated in HL. Excellent response rates in heavily
pretreated patients were observed with the ADC brentuximab vedotin directed against CD30. Thus,
ongoing trials investigate brentuximab vedotin in different additional indications. One example is the firstline treatment of advanced HL where the drug is currently being evaluated in combination with variants of
the first-line protocols ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP
(bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). Anti-CD20
antibodies given either as single agent or in combination with conventional chemotherapy have also been
investigated and still undergo investigation in prospective studies including HL patients. This article
reviews the available data on treatment approaches including antibodies and ADC in HL patients.
Key words classical Hodgkin lymphoma; nodular lymphocyte-predominant Hodgkin lymphoma; antibody; antibody-drug conjugate;
CD20; CD30
Correspondence Dennis A. Eichenauer, MD, First Department of Internal Medicine, University Hospital Cologne, D-50937 Cologne,
Germany. Tel: +0049 (0)221 478 0; Fax: +0049 (0)221 478 88188; e-mail: dennis.eichenauer@uk-koeln.de
Accepted for publication 10 April 2014

Hodgkin lymphoma (HL) is a B cell-derived lymphoid

malignancy with an incidence of 23/100 000/yr. Young
adults aged 2040 are most often affected. Histologically,
classical HL (cHL) accounting for about 95% of all HL
cases is distinguished from nodular lymphocyte-predominant
HL (NLPHL) representing about 5% of all HL cases (1).
The two histological subtypes substantially differ in terms of
immunophenotype and clinical course. While the
disease-dening Hodgkin and Sternberg-Reed (H-RS) cells
in cHL consistently express CD15 and CD30, occasionally
stain positive for CD20 and lack CD45, the malignant
lymphocyte-predominant cells (LP) in NLPHL are positive
for CD20 and CD45 but lack CD15 and CD30 (2). The

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

doi:10.1111/ejh.12347

clinical course of NLPHL often resembles low-grade nonHodgkin lymphoma (NHL) and is thus more indolent than
in cHL (3).
Due to the development of highly active multiagent chemotherapy regimens such as ABVD (adriamycin, bleomycin,
vinblastine, dacarbazine) or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine,
procarbazine, prednisone) as well as the optimization of
radiotherapy (RT) eld and doses, HL has become highly
curable and about 80% of patients remain relapse-free after
adequate rst-line treatment. Even in case of relapse, up to
50% of patients can be salvaged successfully and achieve
long-term remission with aggressive second-line treatment

Antibodies and ADC in HL

consisting of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) (4). In contrast,
patients with disease recurrence after high-dose chemotherapy have a dismal prognosis and treatment options are limited (57). Thus, there is a need for novel approaches in this
patient group. Such approaches may include antibodies and
antibody-drug conjugates (ADC) (Fig. 1). In cHL, particularly CD30 targeting appears promising as this antigen is
highly and almost selectively expressed on the malignant HRS cells (8).
Patients with newly diagnosed cHL may also benet from
the use of immunotherapy directed against CD30 as the rate
of therapy-related acute and long-term toxicity might be
lower than with conventional chemotherapy due to the targeted mode of action. Thus, prospective studies currently
evaluate variants of ABVD and BEACOPPescalated in combination with the ADC brentuximab vedotin directed against
CD30 as frontline treatment in patients with newly diagnosed cHL (9, 10).
Given the consistent expression of CD20 on the malignant
LP cells, the activity of single-agent anti-CD20 antibody
treatment has been investigated in several smaller phase II
studies including NLPHL patients. Response rates were
close to 100% in both newly diagnosed and relapsed
patients, but remissions were often not durable (1113).
Therefore, it is necessary to optimize the use of anti-CD20
antibodies in NLPHL.
This article gives an overview of recent prospective studies evaluating antibodies and ADC in HL.
Targeting CD30
Monoclonal antibodies

After it had been shown that CD30 is almost selectively

expressed on H-RS cells in cHL, efforts were made to use
this antigen as therapeutic target (14). Several monoclonal

Figure 1 Mechanism of action of antibody-drug conjugates (ADC).

Eichenauer and Engert

anti-CD30 antibodies were prospectively evaluated in phase

I and phase II studies.
The chimeric anti-CD30 antibody SGN-30 underwent clinical evaluation after preclinical data had shown promise (15,
16). Safety and feasibility of SGN-30 treatment were shown
in a phase I dose escalation study including 21 HL patients
and three patients with CD30-positive non-Hodgkin lymphoma (NHL) so that a phase II study including 38 HL
patients and 41 patients with anaplastic large cell lymphoma
(ALCL) was initiated (17, 18). Patients were heavily pretreated and had a median of three prior lines of treatment.
Generally, results were disappointing. Among the HL
patients included, no objective response was observed. Disease stabilization was seen in 29% (11/38) of cases.
A randomized phase II study also evaluated SGN-30 in
combination with the GVD (gemcitabine, vinorelbine, pegylated liposomal doxorubicin) regimen in patients with
relapsed HL. The trial had to be closed prematurely due to
an increased rate of pulmonary events. In terms of efcacy,
the response rate among patients receiving the combination
treatment did not differ from the response rate observed in
patients treated with GVD alone (19). Given these data, no
further clinical studies investigating of SGN-30 either alone
or in combination with conventional chemotherapy were
conducted.
The fully human anti-CD30 antibody MDX-060 had
shown promising preclinical activity and was subsequently
investigated in a phase I/II study including a total of 72
patients with HL (n = 63) or CD30-positive NHL (n = 9)
(20, 21). Patients had received a median of four prior lines
of treatment including high-dose chemotherapy and ASCT
in most cases. Treatment with MDX-060 was well tolerated.
However, the observed clinical activity was limited. Only
6% (4/63) of the HL patients treated within the study
responded.
More recently, trials with second-generation anti-CD30
antibodies were conducted. An interim analysis of a phase I
trial evaluating the defucosylated fully human anti-CD30
antibody MDX-1401 included 12 HL patients. While the tolerability was good, the clinical activity was poor again with
no patient achieving an objective response; eight patients
had disease stabilization; and four patients progressed under
treatment (22). XmAb2513 is another second-generation
anti-CD30 antibody that underwent clinical evaluation in
HL. At present, preliminary feasibility and response data
from 13 patients enrolled in a phase I study are available.
Treatment was well tolerated, and tumor reduction was
observed in three cases (23). Final results of both the MDX1401 trial and the XmAb2513 study are pending.
With the aim to increase the cytotoxic potential by recruiting natural killer (NK), bispecic antibodies targeting CD30
and CD16 were developed and investigated in clinical studies. A total of 15 patients with relapsed or refractory HL
were included in a phase I/II study already conducted in the

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Eichenauer and Engert

1990s. Treatment-related side effects were rare, and some

activity (1 complete remission (CR), one partial remission
(PR), three minor responses, one mixed response) was
observed. However, nine patients developed anti-mouse antibodies so that immunogenicity represented a relevant problem precluding prolonged and repeated treatment (24).
A bispecic molecule consisting of fragments derived
from the anti-CD30 antibody Ki-4 and the anti-CD64 antibody H22 was also evaluated in a phase I study including
10 patients with relapsed and refractory HL. Treatment with
the molecule was well tolerated with only mild and transient
side effects. Responses or disease stabilization were seen in
some patients (one CR, two PR and four stable diseases
(SD)) (25). However, no further investigation of the drug
was undertaken.
More recently, the bispecic antibody AFM-13 directed
against CD30 and CD16a was investigated in a phase I
study including 28 patients with relapsed HL. Patients were
heavily pretreated and had a median of six prior therapies. A
total of two patients achieved PR, and 13 patients had disease stabilization (26). Given these results, the drug will
undergo further investigation in a phase II trial. Based on
the pharmacokinetic data obtained from the phase I study,
the dosing schedule within the phase II study will be modied to optimize the therapeutic efcacy.
Immunotoxins and antibody-drug conjugates (ADC)

Immunotoxins composed of antibodies and cytotoxic plant

or bacterial toxins were evaluated in clinical trials in the
1990s. In patients with relapsed and refractory HL or ALCL,
an immunotoxin consisting of deglycosylated ricin A-chain
and the anti-CD30 antibody Ki-4 was investigated in a phase
I dose escalation study including 17 patients. Among 15
evaluable patients, one PR, one minor response and two SD
were observed. Side effects occurred frequently and included
vascular leak syndrome, fatigue, tachycardia and others. In
addition, some patients developed anti-ricin and anti-mouse
antibodies (27). Due to the moderate clinical activity and the
rather frequent development of side effects, this immunotoxin did not undergo further evaluation.
In 2003, initial data from cell line and mouse experiments
evaluating an ADC consisting of the anti-CD30 antibody
cAC10 and the antimitotic agent monomethyl auristatin E
(MMAE) became available (28). The results were convincing and led to the investigation of the drug within prospective clinical studies. Within these studies, the drug was used
under the name brentuximab vedotin. A dose escalation
phase I study included 45 patients with heavily pre treated
CD30-positive lymphomas (42 HL, two ALCL, one angioimmunoblastic T-cell lymphoma (AITL)) who received
brentuximab vedotin every 3 wks at doses between 0.1 and
3.6 mg/kg of body weight. The maximum tolerated dose
was 1.8 mg/kg. In this trial, there were 17 responses (11

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Antibodies and ADC in HL

CR, seven PR), and tumor regression was observed in 86%

of all patients. The median progression-free survival (PFS)
was 5.9 months. Adverse events including peripheral neuropathy, fatigue, pyrexia and neutropenia were mostly mild
and manageable (29).
The excellent results from the phase I study were the basis
for a pivotal phase II study including 102 HL patients who
had failed high-dose chemotherapy followed by ASCT. The
majority of patients within this phase II study presented with
poor-risk features. Thus, the median time to relapse after
ASCT was only 6.7 months. Study treatment consisted of
brentuximab vedotin at 1.8 mg/kg every 3 wks. Up to 16
cycles were given. The overall response rate (ORR) was
75% with 34% of patients achieving CR. Tumor reductions
were observed in 94% of study participants (Fig. 2). After a
median follow-up of 18.5 months, the median overall PFS
was 5.6 months and thus similar to the phase I study. However, among patients achieving a CR, the median PFS was
21.7 months (30). These results compared favorably with
those observed with other novel drugs such as the immunomodulatory drug lenalidomide, the histone deacetylase
(HDAC) inhibitor panobinostat and the mammalian target of
rapamycin (mTOR) inhibitor everolimus that recently underwent clinical evaluation in HL patients with multiple
relapses (3133). Therefore, brentuximab vedotin was
approved for the treatment of HL patients relapsing after
high-dose chemotherapy and ASCT by the Food and Drug
Administration (FDA) and the European Medicine Agency
(EMEA).
Further analyses performed by different groups conrmed
the results from the pivotal phase II study (34, 35). In addition, brentuximab vedotin was shown to exhibit signicant
activity in transplant-nave patients, patients prior to allogeneic stem cell transplantation (aSCT), patients relapsing after
aSCT and patients aged above 60 yr (3640). Recently,
results of a prospective study investigating brentuximab vedotin retreatment in HL and ALCL were published. A total

Figure 2 Tumor reduction after single-agent brentuximab vedotin

treatment in cHL patients failing high-dose chemotherapy and autologous stem cell transplantation (ASCT).

Antibodies and ADC in HL

Eichenauer and Engert

of 29 patients (21 HL, eight ALCL) who had relapsed after

achieving CR or PR with brentuximab vedotin within a previous trial were included in this study. Median time from
the last brentuximab vedotin dose to enrollment in the retreatment study was 8 months. Among the 20 HL patients
who were evaluable for efcacy analysis, 12 (60%) had
responded (six CR, six PR). The median response duration
among patients responding to brentuximab vedotin retreatment was 9.4 months. Side effects were similar to those
seen after initial treatment. However, the rate of peripheral
neuropathy appeared to be higher than after initial brentuximab vedotin treatment so that extended brentuximab vedotin exposure should be closely monitored for this adverse
effect (41).
Ongoing or recently nished clinical trials investigate
brentuximab vedotin in further indications ranging from
rst-line treatment to the treatment of patients with multiple
relapses. A phase III trial (NCT01712490) randomly compares classical ABVD with a combination of brentuximab
vedotin and AVD in patients with newly diagnosed
advanced HL (Table 1). Previously, a phase I/II study had
shown an excellent response rate of 95% for the combination of brentuximab vedotin and ABVD or AVD in this
patient group. However, the combination of brentuximab
vedotin and ABVD was associated with an unacceptably
high rate of serious pulmonary events. Therefore, the protocol was modied, and patients subsequently received brentuximab vedotin combined with AVD until accrual was
completed. Response rates appeared not to be compromised
by the omission of bleomycin, and no more pulmonary
events occurred after switching from ABVD to AVD (9). Of
note, brentuximab vedotin is given at a dose of 1.2 mg/kg
every 2 wks when combined with AVD.
A randomized phase II trial (NCT01569204) that completed recruitment recently evaluated brentuximab vedotin in
combination with two variants based on a BEACOPPescalated
backbone (Table 1). According to data from an interim
analysis, these regimens might be equally effective and less
toxic as compared with conventional BEACOPPescalated (10).
However, mature results are pending.
Two trials (NCT01508312 and NCT01393717) aim at
answering the question whether single-agent brentuximab

vedotin is sufcient as salvage therapy prior to high-dose

chemotherapy and ASCT in patients with relapsed HL. Data
from these trials are not yet available.
Within the randomized AETHERA trial (NCT01100502)
that already nished accrual, high-risk patients with relapsed
HL who underwent high-dose chemotherapy and ASCT
were randomized between brentuximab vedotin maintenance
at a dose of 1.8 mg/kg every 3 wks for up to 16 cycles or
placebo. Results from this trial are awaited in the near
future.
In addition, several ongoing trials including HL patients
with multiple relapses investigate brentuximab vedotin in
combination with other novel drugs such as temsirolimus
(NCT01902160) or ipilimumab (NCT01896999) and conventional chemotherapeutics such as bendamustine
(NCT01874054) or gemcitabine (NCT01780662) (Table 1).
Targeting CD20
Anti-CD20 antibodies in cHL

Although the disease-dening H-RS cells do not consistently

express CD20, there appears to be a rationale for the use of
anti-CD20 antibodies in cHL. This is due to the fact that
cells of the tumor microenvironment in HL were shown to
play an important role for tumor survival and progression.
These cells are frequently positive for CD20.
The MD Anderson Cancer Center (MDACC) conducted a
pilot study investigating single-agent rituximab in 22 heavily
pretreated cHL patients (Table 2). After six weekly doses of
rituximab at 375 mg/m2, 22% of patients had responded.
The median duration of response was 7.8 months, and
response did not correlate with the CD20 status on the H-RS
cells (42).
Within a phase II study also conducted at the MDACC,
rituximab was evaluated in combination with gemcitabine
(Table 2). A total of 33 relapsed patients with a median of
three prior therapies were enrolled. Eighteen of them had
failed high-dose chemotherapy and ASCT. Treatment consisted of rituximab at 375 mg/m2 given for six consecutive
weeks and gemcitabine at 1250 mg/m2 given on days 1 and
8 of each 21-day cycle for a maximum of six cycles. An

Table 1 Ongoing clinical studies evaluating brentuximab vedotin in combination with conventional chemotherapy or novel drugs
Regimen

Patient group

Study

Reference

Brentuximab vedotin + AVD

Newly diagnosed,
advanced stages
Newly diagnosed,
advanced stages
Relapsed
Relapsed
Relapsed
Relapsed

Randomized phase III

NCT01712490

Randomized phase II

(10) (NCT01569204)

Single-arm phase I/II

Single-arm phase I/II
Phase I
Phase I

NCT01874054
NCT01780662
NCT01902160
NCT01896999

Brentuximab vedotin + BEACOPP variants

Brentuximab
Brentuximab
Brentuximab
Brentuximab

vedotin + bendamustine
+ gemcitabine
vedotin + temsirolimus
vedotin + ipilimumab

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Eichenauer and Engert

Antibodies and ADC in HL

Table 2 Clinical studies with rituximab in cHL and NLPHL

Histology

Patient group

Treatment

cHL
cHL
cHL
cHL/NLPHL

Relapsed
Relapsed
Newly diagnosed, advanced stages
Newly diagnosed, advanced stages
with positive PET after 2 cycles of
BEACOPPescalated
Relapsed
Newly diagnosed, stage IA without RF
Newly diagnosed and relapsed, all stages

Rituximab
Rituximab
Rituximab
Rituximab

NLPHL
NLPHL
NLPHL

objective response was seen in 48% of patients. However,

with a median of 2.7 months, responses were not durable.
Thus, tumor control with the combination of rituximab and
gemcitabine was worse than expected (43).
The combination of rituximab and classical rst-line regimens was also investigated in clinical trials. In two singlearm phase II studies, patients with newly diagnosed cHL
were treated with rituximab in combination with ABVD
(R-ABVD) (Table 2). The smaller trial included 49 patients
with stage II-IV disease (20 stage II, 18 stage III, 11 stage
IV). Treatment consisted of six cycles of R-ABVD in 48
patients and two cycles of R-ABVD in one patient. Rituximab was given on days 1, 8, 15 and 22 of the rst cycle of
ABVD and on day 1 of the 2nd, 4th and 6th cycle. After a
median follow-up of 33 months, the 3-year estimates for
EFS and OS were 83% and 98%, respectively. Of note, only
four patients treated within this trial required consolidating
RT after R-ABVD treatment (44).
The larger study included 85 patients with advanced cHL
of whom 78 (28 stage II, 24 stage III, 26 stage IV) were eligible for the nal analysis. Treatment consisted of a total of
six cycles of ABVD. In addition, standard dose rituximab
was given for six consecutive weeks. The rst rituximab
dose was given on day 1 of the rst cycle of ABVD. Within
this study, 93% of patients achieved CR or CR unconrmed
(CRu). After a median follow-up of 68 months, the 5-yr
EFS and OS rates were 83% and 96%, respectively (45).
Based on these results, a randomized phase II study
(NCT00654732) (Table 2) comparing the conventional
ABVD protocol and R-ABVD in patients with poor-risk
(International Prognostic Score (IPS) >2) advanced cHL was
initiated. The trial already nished recruitment but results
are pending.
Within the ongoing GHSG HD18 trial (NCT00515554),
patients with newly diagnosed advanced HL initially
receive two cycles of BEACOPPescalated.Then, interim PET
is performed, and patients are randomized (Table 2). The
standard arm of the study consists of a total of six cycles
of BEACOPPescalated irrespective of the result of the interim
PET. In the experimental arm, patients with a complete
metabolic response receive a total of only four cycles of

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Reference
alone
+ gemcitabine
+ ABVD
+ BEACOPPescalated

Rituximab alone
Rituximab alone
Rituximab alone (limited or
extended schedule)

(42)
(43)
(44, 45) (NCT00654732)
(NCT00515554)

(11)
(12)
(13)

BEACOPPescalated. In contrast, patients with metabolically

active residual disease after two cycles of BEACOPPescalated
received a total of six cycles of escalated BEACOPP supplemented by rituximab in the cycles given after the
interim PET until this study arm was closed according to
plan.
Anti-CD20 antibodies in NLPHL

In contrast to cHL, the malignant LP cells in NLPHL consistently express CD20. Thus, anti-CD20 antibody treatment
represents a promising approach in this rare histological subtype. Several smaller phase II studies evaluating rituximab
and follow-up products in relapsed and newly diagnosed
NLPHL have been initiated.
A phase II study conducted by the GHSG included 15
patients with biopsy-proven relapsed NLPHL (Table 2).
Patients received four weekly standard doses of rituximab.
The ORR was 94%. After a median follow-up of 63 months,
the median time to progression was 33 months, and the
median OS was not reached (11). Treatment results of 11
relapsed NLPHL patients included in a phase II trial conducted by the Stanford Group (Table 2) and treated with
four weekly standard doses of rituximab were slightly worse.
The ORR was 100%, and the median PFS 41 months. After
a median follow-up of 9.8 yr, 5-yr PFS and OS rates were
36.4% and 90.9%, respectively. Within this trial, seven additional patients with relapsed NLPHL were treated with four
weekly standard doses of rituximab followed by rituximab
maintenance consisting of four weekly doses every 6 months
for 2 yr. After a median follow-up of 4.2 yr, 5-yr PFS and
OS rates were both 71.4%. The median PFS was 76 months
(13). Given the results of the GHSG and the Stanford Group
studies, rituximab alone represents a reasonable treatment
option for patients with relapsed NLPHL, particularly for
those with a low tumor burden at relapse. However, to shed
more light on the role of anti-CD20 antibodies in relapsed
NLPHL, the GHSG initiated a trial investigating the fully
human anti-CD20 antibody ofatumumab (NCT01187303).
This trial recently completed recruitment, and rst results are
expected within the near future.

Antibodies and ADC in HL

In newly diagnosed NLPHL, treatment with single-agent

rituximab was also investigated in prospective studies.
Examples include a GHSG phase II study including 28
patients with newly diagnosed stage IA NLPHL who were
treated with four weekly rituximab doses at 375 mg/m2
(Table 2). All patients responded. However, after a median
follow-up of 43 months, 25% of patients had relapsed (12).
Thus, the relapse rate was higher than with the current standard of care for stage IA NLPHL consisting of RT alone so
that rituximab alone was not adopted as novel treatment of
choice in this setting (46, 47). The Stanford Group trial
mentioned above included 21 patients with previously
untreated stage I-III NLPHL. The 5-yr PFS and OS rates
were 41.7% and 100%, respectively, for patients treated with
four standard doses of rituximab and 51.9% and 100%,
respectively, for patients receiving four standard doses of rituximab followed by rituximab maintenance every 6 months
for 2 yr. The median PFS rates were 21 months and
67 months for patients receiving limited and extended rituximab treatment, respectively (13). Thus, single-agent rituximab appears to be associated with a signicantly poorer
tumor control as compared with conventional chemotherapy
and/or RT when given in newly diagnosed NLPHL (3). In
contrast, the combination of rituximab with conventional
chemotherapy seems to be effective in the rst-line treatment
of NLPHL as suggested by a retrospective analysis from the
MDACC including a total 20 patients treated with R-CHOP
(rituximab, cyclophosphamide, adriamycin, vincristine, prednisone) optionally followed by involved-eld RT (IF-RT).
All patients had responded, and no relapses had occurred
after a median follow-up of 42 months (48). However, these
results were not yet conrmed by a prospective study.
Summary

In HL, antibodies and ADC directed against CD30 and CD20

have been evaluated in prospective clinical studies either as
single agent or in combination with conventional chemotherapy. While treatment results among cHL patients treated with
naked anti-CD30 antibodies were disappointing, excellent
response rates were observed with the ADC brentuximab vedotin when given as single agent in heavily pretreated patients.
Thus, brentuximab vedotin is currently undergoing further
prospective investigation in different indications and will
likely become part of future treatment strategies in both newly
diagnosed and relapsed cHL. The role of anti-CD20 antibodies
in cHL is unclear. However, results from prospective studies
evaluating rituximab in combination with conventional chemotherapy regimens will become available soon and possibly
allow valid conclusions regarding the value of anti-CD20
antibodies in the treatment of cHL.
In NLPHL, response rates after single-agent treatment with
the anti-CD20 antibody rituximab are excellent. In relapsed
disease, anti-CD20 antibody treatment alone appears to be

Eichenauer and Engert

sufcient in a relevant proportion of patients and results are

similar to those observed with high-dose chemotherapy followed by ASCT (49). In newly diagnosed NLPHL, the standard of care still consists of chemotherapy and/or RT due to
the better tumor control in comparison with rituximab alone.
Due to the lack of CD30 on the malignant LP cells in
NLPHL, anti-CD30 antibodies or ADC directed against
CD30 do not represent a treatment option in NLPHL.
Generally, the implementation of antibodies and ADC into
treatment algorithms in HL may not only improve the treatment efcacy. The risk of acute and long-term toxicity might
also be reduced. This is particularly important as late sequelae including infertility, heart failure and secondary solid
and hematological malignancies do not only impair the quality of life but are also responsible for a relevant proportion
of deaths among HL survivors (5054).
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