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ADJUSTMENT OF THERAPY FOR HODGKIN LYMPHOMA BASED ON INTERIM PET IS BENEFICIAL AND RADIOTHERAPY MAY BE SUBSTITUTED WITH CHEMOTHERAPY IN PATIENTS WITH NEGATIVE INTERIM STUDY: FINAL RESULTS OF H2 TRIAL
Author(s): ,
Eldad J Dann
Affiliations:
Blood Bank and Apheresis Unit,RAMBAM HEALTH CARE CAMPUS,Haifa,Israel
,
Osnat Bairey
Affiliations:
Rabin Medical Center,Petach Tikva,Israel
,
Rachel Bar-Shalom
Affiliations:
Shaare Zedek Medical Center,Jerusalem ,Israel
,
Tania Mashiach
Affiliations:
RAMBAM HEALTH CARE CAMPUS,Haifa,Israel
,
Elinor Barzilai
Affiliations:
RAMBAM HEALTH CARE CAMPUS,Haifa,Israel
,
Abraham Korenberg
Affiliations:
Assaf Harofeh Medical Center,Zerifin,Israel
,
Luiza Akria
Affiliations:
Galil Medical Center,Nahariya,Israel
,
Tamar Tadmor
Affiliations:
Bnai Zion Medical Center,Haifa,Israel
,
Kalman Filanovsky
Affiliations:
Kaplan Medical Center,Rehovot,Israel
,
Uri Abadi
Affiliations:
Meir Medical Center,Kfar Saba,Israel
,
Olga Kagna
Affiliations:
RAMBAM HEALTH CARE CAMPUS,Haifa,Israel
,
Rosa Ruchlemer
Affiliations:
Shaare Zedek Medical Center,Jerusalem ,Israel
,
Roxolyana Abdah-Bortnyak
Affiliations:
RAMBAM HEALTH CARE CAMPUS,Haifa,Israel
,
Neta Goldschmidt
Affiliations:
Hadassah Medical Center,Jerusalem ,Israel
,
Ron Epelbaum
Affiliations:
RAMBAM HEALTH CARE CAMPUS,Haifa,Israel
,
Netanel A Horowitz
Affiliations:
RAMBAM HEALTH CARE CAMPUS,Haifa,Israel
,
David Lavie
Affiliations:
Hadassah Medical Center,Jerusalem ,Israel
,
Dina Ben-Yehuda
Affiliations:
Hadassah Medical Center,Jerusalem ,Israel
,
Ofer Shpilberg
Affiliations:
Assuta Medical Center,Tel-Aviv,Israel
Ora Paltiel
Affiliations:
Hadassah Medical Center,Jerusalem ,Israel
(Abstract release date: 05/19/16) EHA Library. Dann E. 06/10/16; 135140; S107
Prof. Eldad Dann
Prof. Eldad Dann
Contributions
Abstract
Abstract: S107

Type: Oral Presentation

Presentation during EHA21: On Friday, June 10, 2016 from 12:00 - 12:15

Location: Hall A2

Background
 The main goal of therapy for Hodgkin lymphoma (HL) is to maximize response while minimizing long-term treatment-related toxicity.

Aims
The study aimed to explore the effect of therapy adjustment based on  early interim PET/CT (PET-2) on the HL patient outcome.

Methods
This prospective multicenter study recruited patients (pts) between 9/2006-8/2013. Pts with classic HL aged 18-60 years, stages I-IV were eligible. Early HL (ED) was categorized into favorable (EF) and unfavorable (EU) disease. After 2 ABVD cycles, pts with EF and negative PET-2 underwent involved site radiation therapy (ISRT) and EU pts received 2 more ABVD cycles (total 4) followed by ISRT In pts with negative PET-2, ISRT could be substituted by two further ABVD courses. Pts with positive PET-2 received a total 4 or 6 ABVD courses for EF and EU, respectively, followed by obligatory ISRT. Pts with advanced HL (AD) (B symptoms or stages III/IV) were assigned to therapy based on IPS: those with IPS 0-2 initially received ABVDx2 while pts with IPS ≥ 3 received escalated BEACOPP (EB) x2. If PET-2 was negative, therapy was completed using ABVDx4. If PET-2 was positive, therapy was escalated to EB with ISRT given to bulky mediastinal masses. A dynamic visual score (DS) comparing PET-2 to baseline PET was used for decision-making regarding therapeutic changes  (Dann et al, Haematologica, 2010).Briefly, for pts with an initial single site of uptake, PET-2 was considered positive if the intensity of residual uptake was ≥ normal mediastinal or liver blood pool (the hottest of the two). For pts with multiple initial sites of HL, disappearance of uptake in all sites or a residual single site uptake with markedly lower intensity on PET-2 was considered a negative result. The Deauville score (performed post-hoc) less or equal to 3 was defined as negative.

Results
HL progression was documented in 50 out of 355 pts, of whom 42 relapsed and 8 had primary progressive disease. PET-2 was negative in 86% and positive in 7% of pts, according to both DS and Deauville score (93% concordance by both systems; kappa 0.627).  At a median follow-up of 47 months (4-114), among  170 ED pts a highly significant difference in the 5-year progression-free survival (PFS) was demonstrated between those with negative and positive PET-2 [0.91 and 0.68, respectively; hazard ratio (HR) 3.66; 95% CI 1.4-9.7; p=0.009] by DS. The differences were even more marked after re-assessment using the Deauville criteria (0.91 compared to 0.47,HR 7.6; 95% CI 2.7-21.4 P<0.001). The 5-year PFS for pts with a negative PET-2 who did not receive ISRT was 0.94 compared to 0.89 for the group receiving ISRT. In the AD group (n=185), 18% (n=33) of pts progressed and 15% (n=27) had a positive PET-2. The 5-year PFS for the whole group, PET-2 negative and positive subgroups was 0.80, 0.82 and 0.68, respectively (p=0.07).  The 5-year OS for ED and AD groups was 0.99 and 0.97, respectively.

Conclusion
Seventy six percent of relapses still occur in pts with a negative PET-2. A positive PET-2 portends an adverse prognosis at all stages of HL. ED pts with positive PET-2 have a poor prognosis if their therapy is continued with ABVD followed by ISRT. ISRT does not appear to improve the outcome for ED pts with negative PET-2. The prognosis of AD patients with positive PET-2 could be improved with administration of 4 additional EB cycles. If PET-2 is negative, EB can be safely changed to ABVD in AD pts.

Session topic: First-line treatment of Hodgkin Lymphoma

Keyword(s): Hodgkin's lymphoma, PET
Abstract: S107

Type: Oral Presentation

Presentation during EHA21: On Friday, June 10, 2016 from 12:00 - 12:15

Location: Hall A2

Background
 The main goal of therapy for Hodgkin lymphoma (HL) is to maximize response while minimizing long-term treatment-related toxicity.

Aims
The study aimed to explore the effect of therapy adjustment based on  early interim PET/CT (PET-2) on the HL patient outcome.

Methods
This prospective multicenter study recruited patients (pts) between 9/2006-8/2013. Pts with classic HL aged 18-60 years, stages I-IV were eligible. Early HL (ED) was categorized into favorable (EF) and unfavorable (EU) disease. After 2 ABVD cycles, pts with EF and negative PET-2 underwent involved site radiation therapy (ISRT) and EU pts received 2 more ABVD cycles (total 4) followed by ISRT In pts with negative PET-2, ISRT could be substituted by two further ABVD courses. Pts with positive PET-2 received a total 4 or 6 ABVD courses for EF and EU, respectively, followed by obligatory ISRT. Pts with advanced HL (AD) (B symptoms or stages III/IV) were assigned to therapy based on IPS: those with IPS 0-2 initially received ABVDx2 while pts with IPS ≥ 3 received escalated BEACOPP (EB) x2. If PET-2 was negative, therapy was completed using ABVDx4. If PET-2 was positive, therapy was escalated to EB with ISRT given to bulky mediastinal masses. A dynamic visual score (DS) comparing PET-2 to baseline PET was used for decision-making regarding therapeutic changes  (Dann et al, Haematologica, 2010).Briefly, for pts with an initial single site of uptake, PET-2 was considered positive if the intensity of residual uptake was ≥ normal mediastinal or liver blood pool (the hottest of the two). For pts with multiple initial sites of HL, disappearance of uptake in all sites or a residual single site uptake with markedly lower intensity on PET-2 was considered a negative result. The Deauville score (performed post-hoc) less or equal to 3 was defined as negative.

Results
HL progression was documented in 50 out of 355 pts, of whom 42 relapsed and 8 had primary progressive disease. PET-2 was negative in 86% and positive in 7% of pts, according to both DS and Deauville score (93% concordance by both systems; kappa 0.627).  At a median follow-up of 47 months (4-114), among  170 ED pts a highly significant difference in the 5-year progression-free survival (PFS) was demonstrated between those with negative and positive PET-2 [0.91 and 0.68, respectively; hazard ratio (HR) 3.66; 95% CI 1.4-9.7; p=0.009] by DS. The differences were even more marked after re-assessment using the Deauville criteria (0.91 compared to 0.47,HR 7.6; 95% CI 2.7-21.4 P<0.001). The 5-year PFS for pts with a negative PET-2 who did not receive ISRT was 0.94 compared to 0.89 for the group receiving ISRT. In the AD group (n=185), 18% (n=33) of pts progressed and 15% (n=27) had a positive PET-2. The 5-year PFS for the whole group, PET-2 negative and positive subgroups was 0.80, 0.82 and 0.68, respectively (p=0.07).  The 5-year OS for ED and AD groups was 0.99 and 0.97, respectively.

Conclusion
Seventy six percent of relapses still occur in pts with a negative PET-2. A positive PET-2 portends an adverse prognosis at all stages of HL. ED pts with positive PET-2 have a poor prognosis if their therapy is continued with ABVD followed by ISRT. ISRT does not appear to improve the outcome for ED pts with negative PET-2. The prognosis of AD patients with positive PET-2 could be improved with administration of 4 additional EB cycles. If PET-2 is negative, EB can be safely changed to ABVD in AD pts.

Session topic: First-line treatment of Hodgkin Lymphoma

Keyword(s): Hodgkin's lymphoma, PET

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