Page 1376 - Hematology_ Basic Principles and Practice ( PDFDrive )

1222 Part VII Hematologic Malignancies

bulky disease who may benefit from irradiation. In the GHSG HD15 Deauville 5-Point Scale for the Interpretation of
trial, following six to eight cycles of standard BEACOPP chemo- TABLE Interim and End of Treatment FDG-PET Imaging in
therapy, patients with residual PET-positive disease received IFRT. 75.7 Patients with Hodgkin Lymphoma
PFS at 1 year was 96% for the PET-negative patients who did not
receive IFRT and 85% for the PET-positive group who did receive FDG-PET Uptake Deauville Score
IFRT (p = .011), suggesting a possible role for consolidative RT in No uptake above background 1
this subgroup.
Before any sound conclusions can be made, however, long-term Uptake equal to or below mediastinum 2
follow-up data from these prospective randomized trials are needed Uptake higher than mediastinum but equal to or 3
to better evaluate the risks and benefits of adjuvant RT after initial lower than liver
chemotherapy in this patient population, particularly when consider- Uptake moderately higher than liver 4
ing the late toxicities that are associated with its use, including sec-
ondary malignancy within the treated field and cardiovascular disease Uptake significantly higher than liver and/or 5
(see Long-Term Complications of Treatment in Hodgkin Lymphoma presence of new lesions
section, later). New areas of uptake/New FDG-PET avid lesions X
FDG, F-2-deoxyglucose; PET, positron emission tomography.
18
Consolidative Autologous Transplant
PET-positive after two cycles of initial ABVD, while the GHSG’s
The function of ASCT to enhance outcome in patients with advanced HD18 trial is evaluating the effect of reducing therapy from eight
HL immediately following standard chemotherapy has been investi- cycles of escalated BEACOPP to four cycles of escalated BEACOPP
gated in a number of clinical studies. However, no survival benefit in patients who are interim PET-negative. Results of both of these
with this approach has been demonstrated. Instead, current practice trials are eagerly awaited.
is to reserve high-dose chemotherapy and ASCT for those patients Collectively, these data have indicated that early interim PET is a
who have either progressed through, or relapsed after, first-line powerful predictor of treatment failure for patients with advanced HL
therapy (see Relapsed and Refractory Hodgkin Lymphoma section, and may effectively discriminate individuals with different risk profiles
later). and therefore different treatment needs. The recent Lugano Classifica-
tion recommends PET/CT as standard practice for response assess-
ment in all patients with FDG-avid HL both at the end of treatment
New Directions in the Treatment of Advanced and early on during treatment using the highly reproducible Deauville
2
Hodgkin Lymphoma 5-point scale (Table 75.7). At interim analysis, a score of 1 or 2 rep-
resents complete metabolic response, whereas a score of 4 or 5 repre-
sents partial metabolic response. A score of 3 may or may not reflect
Interim PET a favorable prognosis depending on the timing of assessment, clinical
background, and treatment used. At the end of treatment, residual
The identification of reliable and consistent risk factors is crucial for disease denoted by a score of 4 or 5 represents treatment failure.
the future development of more specific, and therefore more success- The strategy of subsequently utilizing PET response to deescalate
ful, treatment approaches for patients with advanced HL, in which ongoing treatment in the best responders to avoid late toxicity, or to
therapy is tailored to the needs of the individual. Interim PET analysis intensify treatment in patients with suboptimal response, holds great
early on during first-line chemotherapy is being widely investigated potential for the future management of patients with advanced HL;
as a potential means of enhancing this risk-directed approach by however, at present this approach still remains investigational. Long-
allowing initial therapy to be modified according to response. term prospective data from randomized clinical trials are crucial to
The significance of residual FDG-avid disease during treatment evaluate the impact of PET-directed alteration of therapy on OS,
for patients with advanced HL has been well described: In an early before it is considered standard of care for this patient population.
prospective study of patients with newly diagnosed advanced HL, a
positive PET following two cycles of standard ABVD was associated
with a 2-year PFS of 12.8% compared with 95% for those achieving Novel Therapies in Advanced Hodgkin Lymphoma
a PET-negative response (p < .0001). Furthermore, in multivariate
analyses interim PET was found to be more predictive of outcome Although effective, the intensification of chemotherapy based on
15
than IPS score (p < .0001). These early observations have been improved risk-stratification techniques may not be appropriate for all
reproduced in parallel studies using escalated BEACOPP. patients with HL. The development of novel targeted therapies has
Clinical studies have since explored the role of interim PET as a recently led to important advances in cancer care by allowing the
tool for directing early, response-based, treatment modifications and provision of effective specific biologic agents which are not associated
have attempted to investigate the effect of this on patient outcome. with the same toxic complications as traditional chemotherapy. This
15a
In a retrospective analysis by Gallamini et al in 2011, the outcome approach may be particularly beneficial for those with less favorable
of patients remaining PET-positive following two cycles of standard performance scores in whom traditional doses of intensive chemo-
ABVD, who went on to receive treatment intensification with therapy are deemed intolerable. One approach, which is currently
BEACOPP, was better than that of ABVD-treated historic controls. being evaluated to further improve outcomes in patients with
15b
In a contrasting study by Avigdor et al in 2010, patients achieving advanced HL, is the incorporation of novel targeted agents into less
a PET-negative remission following two cycles of escalated BEACOPP intense frontline chemotherapy regimens.
underwent deescalation of treatment to ABVD and in this group, The recent success of BV in the treatment of relapsed/refractory
despite attenuation of treatment, the 4-year PFS was maintained at HL (see Relapsed and Refractory Hodgkin Lymphoma section, later)
87%, implying that in this PET-negative population similar efficacy has prompted efforts to explore its role when combined with standard
can be achieved with a less toxic approach. chemotherapy in the upfront treatment of newly diagnosed advanced
At present two large randomized control trials are underway to HL. In a phase I safety study including patients with newly diagnosed,
further determine the role of PET-directed therapy in the future treatment-naive advanced HL, escalating doses of Brentuximab
management of patients with advanced HL. The RATHL trial Vedotin were added to either an ABVD or modified-AVD backbone
(Response Adapted Therapy using FDG-PET Imaging in Advanced (without bleomycin) for up to six cycles. The maximum tolerated
Hodgkin Lymphoma), conducted by the UK NCRI, is evaluating dose (MTD) of brentuximab when combined with ABVD or AVD
intensification of therapy with BEACOPP in patients who remain was 1.2 mg/kg. In this study CR was achieved in 95% of those