Adcetris – Brentuximab Vedotin
NCCN – National Comprehensive Cancer Network
ADC- Antibody Drug Conjugate
NHL – Non-Hodgkin’s Lymphoma
NLPHL - nodular lymphocyte-predominant Hodgkin lymphoma
cHL- classical Hodgkin’s Lymphoma
CD-30- Antibody expressed in certain cancers
sALCL- systemic Anaplastic Large Cell Lymphoma
PTCL – Peripheral T-Cell Lymphoma
PTCL-NOS – Peripheral T-Cell Lymphoma Not Otherwise Specified.
Auto-HSCT – Autologous Hematopoietic Stem Cell Transplantation
AITL – Angioimmunoblastic T-Cell Lymphoma
ATLL – Adult T-Cell Leukemia/Lymphoma
EATL – Enteropathy associated T-Cell Lymphoma
SPA - Special Protocol Assessment
EMA - European Medicines Agency
CHP – Cyclophosphamide Doxorubicin & Prednisone
CHOP - Cyclophosphamide Doxorubicin Vincristine & Prednisone
CHOEPMF – Mycoides Fungoides
MMAE- Microtubule-disrupting agent Monomethyl Auristatin E
LDH – Serum Lactate Dehydrogenase
HSCT – Human Stem Cell Treatment?
PFS – Progression-Free Survival
mPFS – Modified Progression-free survival --- a more rigorous measure of the effectiveness of frontline therapy versus
standard PFS. Standard PFS may overestimate the effectiveness of frontline therapy due to the inclusion of patients who
may have benefited from additional chemotherapy and/or radiotherapy following frontline treatment
EFS – Event-free Survival
FFS – Failure-Free Survival
CR – Complete Remission
ALK –
eBEACOPP - escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
auto-HSCT or HCT - autologous hematopoietic stem cell transplantation.
ABVD - doxorubicin, bleomycin, vinblastine, dacarbazine – Most common chemo treatment for stage III-IV cHL
MOPP - mechlorethamine, vincristine, procarbazine, and prednisone
Hodgkins Lymphoma
KEY CONCEPTS
Hodgkin lymphoma (HL) is a type of lymphoma, or a hematologic malignancy, that arises in the
lymphatic system.
There are 2 main histologic subtypes of HL, classical HL and NLPHL, which have different malignant
cells, clinical presentations, and disease courses.
In 2017 in the United States, there will be an estimated 8260 new cases of HL and 1070 deaths due to HL.
Classical HL staging is based on the Ann Arbor staging system, which primarily classifies HL by the
number of lymph nodes affected and their location.
Approximately 40% of patients have stage III or IV disease at diagnosis.
Based on the Ann Arbor stage and the presence or absence of risk factors, clinicians categorize patients
to 1 of 3 treatment groups: early-stage favorable, early-stage unfavorable, or advanced stage.
Patients with advanced classical HL are at a significant risk of treatment failure and have shorter
lifespans compared to individuals with early-stage disease:
• The 5-year overall survival rates are 80% and 65% for patients with stage III and IV disease,
respectively, compared to up to 90% in patients with stage I or II disease.
• Up to 30% of patients with advanced classical HL relapse following frontline treatment.
Frontline Treatment of cHL
KEY CONCEPTS
Advanced stage classical HL is typically treated with chemotherapy alone and may be followed by
radiation therapy for patients with residual disease.
The ABVD regimen, which is summarized in Table 1, is the standard of care frontline treatment for
advanced classical HL.
The escalated BEACOPP regimen and Stanford V regimen are additional chemotherapy option
available to treat frontline, advanced classical HL, however ABVD remains standard of care due to
efficacy and tolerability.
Early interim PET scan may help identify patients who are not responding to frontline therapy.
• The NCCN guidelines recommendations to perform interim PET/CT restaging was based on the
results from the RATHL clinical trials; however, the NCCN guidelines also state that the value of
interim PET is unclear in many clinical scenarios.
• Interpreting outcomes of PET/CT staging involves the use of the Deauville criteria, a 5-point scale
that helps clinicians assess responses to treatment.
• There are some limitations of a PET-adapted approach, including the fact that three-quarters of the
PFS events in the SWOG S0816 clinical trial occurred in the PFS-negative population.
According to the NCCN guidelines, ABVD is the standard of care frontline treatment for classical HL,
and using early interim PET restaging is the preferred approach for guiding frontline therapy.
The role of consolidative radiation after frontline chemotherapy in patients with stage III-IV HL is not
well-defined.
ECHELON-1 Design and Data
ADCETRIS is an ADC that binds to CD30-expressing cells, is internalized as part of the ADC-CD30
complex, and then releases its covalently linked MMAE molecule. MMAE disrupts the cell’s
microtubule network, leading to cell-cycle arrest and apoptosis.
The phase 1 SGN35-009 trial was critical in determining that ADCETRIS cannot be safely combined with
bleomycin but is generally well tolerated when combined with AVD, leading to a high level of activity
and durable responses.
The phase 3 ECHELON-1 trial demonstrated:
• A+AVD significantly improved modified PFS compared with ABVD
• There was a 23% reduction in the risk of frontline treatment failure in patients treated with A+AVD
compared with ABVD
• When combined with G-CSF primary prophylaxis, A+AVD demonstrated a manageable safety profile
• There was a lower incidence of pulmonary toxicity and associated mortality with A+AVD compared
with ABVD
• One-third fewer patients in the A+AVD arm received subsequent salvage chemotherapy, high-dose
chemotherapy, and transplant versus those in the ABVD treatment arm