GERMAN HODGKIN STUDY GROUP PHASE I TRIAL OF DOXORUBICIN, VINBLASTINE, DACARBAZINE, AND LENALIDOMIDE (AVD-REV) FOR ELDERLY HODGKIN LYMPHOMA PATIENTS ? FINAL ANALYSIS
Author(s): ,
Boris Boell
Affiliations:
Hematology,GHSG, University Hospital,Cologne,Germany
,
Annette Pluetschow
Affiliations:
Hematology,GHSG,Cologne,Germany
,
Dennis Eichenauer
Affiliations:
Hematology,GHSG,Cologne,Germany
,
Bastian von Tresckow
Affiliations:
Hematology,GHSG,Cologne,Germany
,
Johannes Atta
Affiliations:
hematology,University Hospital,frankfurt,Germany
,
Michael Pfreundschuh
Affiliations:
Hematology,University Hospital,Homburg,Germany
,
Feuring-Buske Michaela
Affiliations:
Hematology,University Hospital,Ulm,Germany
,
Martin Vogelhuber
Affiliations:
Hematology,University Hospital,Regensburg,Germany
,
Martin Sökler
Affiliations:
hematology,University Hospital,Tuebingen,Germany
,
Michael Fuchs
Affiliations:
Hematology,GHSG,Cologne,Germany
,
Andreas Engert
Affiliations:
Hematology,GHSG,Cologne,Germany
Peter Borchmann
Affiliations:
Hematology,GHSG,Cologne,Germany
EHA Library. Boell B. 06/14/15; 103189; S805 Disclosure(s): German Hodgkin Study Group
Hematology
Boris Boell
Boris Boell
Contributions
Abstract
Abstract: S805

Type: Oral Presentation

Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15

Location: Room Lehar 3 + 4

Background
About 30% of all Hodgkin Lymphoma (HL) patients are ≥60 years old. ABVD is standard of care for these patients, although outcome and feasibility are poor, one limitation being bleomycin-induced pulmonary toxicity. 

Aims
We thus replaced bleomycin with lenalidomide (Revlimid®), and initiated the AVD-Rev phase-I trial (NCT01569204) for 60-75 year-old patients with 1st diagnosis of early unfavorable- or advanced-stage HL, good performance status (ECOG/WHO ≤2), and no severe organ dysfunction.

Methods
Depending on stage and response at interim staging, patients received 4-8 cycles of AVD-Rev followed by radiotherapy with prophylactic anticoagulation (ASA or heparin). The daily lenalidomide dose for the first patient was 5mg; possible dose levels ranged from 5 to 40mg. Thromboembolism ≥CTC II°, hematological toxicity as severe cytopenia (ANC< 500/μl >7days with G-CSF and thrombocytopenia < 25.000/μl), and complications as neutropenic fever and prolonged therapy delay were considered as dose limiting toxicities (DLT) if they occurred during the first 4 cycles.

Results
 25 patients (median age: 67, range 61-76) and a CIRS-G comorbidity score of up to 7 points (range 0-7) were assigned to dose levels 5mg (n=1), 10mg (n=1), 15mg (n=1), 20mg (n=6), and 25mg (n=16). 15 patients were male, 68% had advanced stage-HL, and 80% had B-symptoms.?After DLT evaluation of 20 patients, a pre-specified stopping criterion was reached with a recommended dose for a phase II trial of 25mg.?Dose delivery was high with a median relative dose intensity of 97% (range 49%>104%; mean 91%). However, CTC III°-IV° toxicities occurred in all 22 patients treated at the 20mg and 25mg dose levels. DLTs were observed in 1 of 6 and 5 of 16 patients at 20mg and 25mg, respectively, and were mainly hematologic but included 3 thromboembolic events despite ASA prophylaxis. No DLT occurred in patients receiving < 20mg lenalidomide. Of note in these vulnerable patients, no treatment related deaths occurred.?Overall response rates were 80% for all patients (20/25) and 86% (19/22) for patients receiving ≥20mg lenalidomide. At 19 months median observation time, 5 patients had disease progression and 4 patients died. The one-year estimates for progression-free (PFS) and overall survival (OS) are 75% [95%> CI: 53-88%] and 92% [95%>CI: 71-98%], respectively. Final results on PFS and OS with two years follow-up will be presented at the EHA congress 2015.

Summary
AVD-Rev is toxic but feasible and highly effective in this vulnerable population of elderly HL patients. 

Keyword(s): Chemotherapy, Elderly, Imids, Immunotherapy

Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects
Abstract: S805

Type: Oral Presentation

Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15

Location: Room Lehar 3 + 4

Background
About 30% of all Hodgkin Lymphoma (HL) patients are ≥60 years old. ABVD is standard of care for these patients, although outcome and feasibility are poor, one limitation being bleomycin-induced pulmonary toxicity. 

Aims
We thus replaced bleomycin with lenalidomide (Revlimid®), and initiated the AVD-Rev phase-I trial (NCT01569204) for 60-75 year-old patients with 1st diagnosis of early unfavorable- or advanced-stage HL, good performance status (ECOG/WHO ≤2), and no severe organ dysfunction.

Methods
Depending on stage and response at interim staging, patients received 4-8 cycles of AVD-Rev followed by radiotherapy with prophylactic anticoagulation (ASA or heparin). The daily lenalidomide dose for the first patient was 5mg; possible dose levels ranged from 5 to 40mg. Thromboembolism ≥CTC II°, hematological toxicity as severe cytopenia (ANC< 500/μl >7days with G-CSF and thrombocytopenia < 25.000/μl), and complications as neutropenic fever and prolonged therapy delay were considered as dose limiting toxicities (DLT) if they occurred during the first 4 cycles.

Results
 25 patients (median age: 67, range 61-76) and a CIRS-G comorbidity score of up to 7 points (range 0-7) were assigned to dose levels 5mg (n=1), 10mg (n=1), 15mg (n=1), 20mg (n=6), and 25mg (n=16). 15 patients were male, 68% had advanced stage-HL, and 80% had B-symptoms.?After DLT evaluation of 20 patients, a pre-specified stopping criterion was reached with a recommended dose for a phase II trial of 25mg.?Dose delivery was high with a median relative dose intensity of 97% (range 49%>104%; mean 91%). However, CTC III°-IV° toxicities occurred in all 22 patients treated at the 20mg and 25mg dose levels. DLTs were observed in 1 of 6 and 5 of 16 patients at 20mg and 25mg, respectively, and were mainly hematologic but included 3 thromboembolic events despite ASA prophylaxis. No DLT occurred in patients receiving < 20mg lenalidomide. Of note in these vulnerable patients, no treatment related deaths occurred.?Overall response rates were 80% for all patients (20/25) and 86% (19/22) for patients receiving ≥20mg lenalidomide. At 19 months median observation time, 5 patients had disease progression and 4 patients died. The one-year estimates for progression-free (PFS) and overall survival (OS) are 75% [95%> CI: 53-88%] and 92% [95%>CI: 71-98%], respectively. Final results on PFS and OS with two years follow-up will be presented at the EHA congress 2015.

Summary
AVD-Rev is toxic but feasible and highly effective in this vulnerable population of elderly HL patients. 

Keyword(s): Chemotherapy, Elderly, Imids, Immunotherapy

Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects

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