In this issue of Leukemia and Lymphoma, Dr. Mocikova and colleagues present the results of a retrospective Czech experience with positron emission tomography (PET or PET/computed tomography [CT]) after induction chemotherapy in patients undergoing high-dose chemotherapy with autologous stem cell support (HD + ASCT) for relapsed or refractory Hodgkin lymphoma (HL) [Citation1]. They included 76 patients treated between 2000 and 2009 in the analysis. Most patients were scanned with CT and single-modality PET (n = 42), while the remaining, more recent patients had dual-modality PET/CT. After salvage therapy, 11 relapses occurred in 20 PET-positive patients and 14 relapses occurred in 56 PET-negative patients. The 2-year progression-free survival (PFS) was significantly higher in PET-negative patients (72.7%) than in PET-positive patients (31.6%). The 2-year overall survival (OS) was also significantly higher in PET-negative patients (90.3% vs. 61.4%). Neither the German Hodgkin Study Group’s secondary clinical risk score nor a complete remission (CR) on CT after induction chemotherapy was significantly associated with PFS or OS.
The results of the present study are in line with previous studies of pre-transplant functional imaging in relapsed patients with HL. Jabbour and co-workers retrospectively studied 211 relapsing patients with HL who were evaluated with PET or gallium scans before HD + ASCT. The 3-year PFS was 69% in patients with negative functional imaging (FI) and 23% in patients with positive FI, while the 3-year OS was 87% and 58%, respectively [Citation2]. More recently, Moskowitz and colleagues published their experience with gallium scanning and PET after induction chemotherapy and before HD + ASCT for relapsed HL. They reported a 5-year event-free survival (EFS) rate of 75% for FI-negative patients and 31% for FI-positive patients [Citation3]. It is noteworthy that both the present study and the previously published studies report a large number of patients in partial remission on CT among the PET-negative patients.
So while a negative pre-transplant PET carries a good prognosis with PFS rates around 70%, the PFS for PET-positive patients seems to be around 30%. The rather poor prognosis of PET-positive patients does not suggest that these patients should not receive HD + ASCT. The Memorial Sloan Kettering Cancer Center’s transplant team have reported favorable outcomes from a strategy where the intensity of induction chemotherapy is based on pretreatment risk stratification [Citation4]. A PET-response adapted salvage therapy could be another way to improve survival for poor-prognosis patients, but there are yet no data to support such a strategy.
In first-line HL therapy, PET seems to have a high prognostic value already after a single cycle of chemotherapy [Citation5]. This could also be true for patients with relapsed HL, and if so, this could allow for non-responding patients to switch to a different, non-cross-resistant induction regimen. From this perspective, a study of PET or PET/CT very early during induction chemotherapy would be interesting.
A number of interesting novel drugs, particularly histone deacetylase (HDAC) inhibitors and SGN-35 (brentuximab vedotin), have shown promising results in heavily pretreated patients with HL [Citation6]. In the near future, these agents are likely to be tested in conjunction with standard induction regimens in order to improve the lymphoma control before HD + ASCT. Large randomized trials are required to demonstrate whether improved tumor control before HD + ASCT will translate into improved survival rates. The results of the current study show PET results as a reliable surrogate for PFS and OS in patients with HL on salvage therapy. This may suggest that the PET-negative rate could be a valid endpoint in phase II trials investigating the addition of novel drugs to the existing induction regimens.
Potential conflict of interest:
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References
- Mocikova H, Pytlik R, Markova J, et al. Pre-transplant positron emission tomography in patients with relapsed Hodgkin lymphoma. Leuk Lymphoma 2011;52:In press.
- Jabbour E, Hosing C, Ayers G, et al. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cancer 2007;109:2481–2489.
- Moskowitz AJ, Yahalom J, Kewalramani T, et al. Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Blood 2010;116:4934–4937.
- Moskowitz CH, Yahalom J, Zelenetz AD, et al. High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol 2010;148:890–897.
- Kostakoglu L, Goldsmith SJ, Leonard JP, et al. FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease. Cancer 2006;107: 2678–2687.
- Jona A, Younes A. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma. Blood Rev 2010; 24:233–238.