UPDATES ON EFFICACY AND SAFETY OF DOSE-DENSE AND DOSE-INTENSE (DD-DI) ABVD AS FRONTLINE THERAPY OF ADVANCED CLASSICAL HODGKIN LYMPHOMA (HL).
(Abstract release date: 05/19/16)
EHA Library. De Lorenzo S. 06/09/16; 135370; LB2259
Dr. Sonya De Lorenzo
Contributions
Contributions
Abstract
Abstract: LB2259
Type: Eposter Presentation
Background
The optimal therapeutic upfront strategy in advanced classic HL hasn’t yet been standardized. In recent years, the scientific community has given greater attention to the concept of dose-intensity and several studies demonstrated that intensifying therapy through dose-escalation of drugs and shortening cycle intervals yields best results than standard ABVD. However, the best frontline approach is still debated and the dispute remains between 2 strategies: 1)The “first hit principle” followed by dose reduction in early responders, 2) The “standard dose” followed by the “second hit” in poor responders.
Aims
Based on the promising results of our recent experience (D’Arco et al, 2015) and of a phase II trial of DD-DI ABVD in advanced HL (Russo et al, 2014) we expanded our previous series and updated follow-up to confirm our findings.
Methods
We treated in frontline, 22 consecutive cases of advanced HL with the ABVD DD-DI protocol (Russo et al, 2014), between June 2011 and December 2015. The drugs were given on days 1 and 11, at the doses of standard ABVD except for doxorubicin (escalated to 35 mg/m2, in the first 4 of 6 cycles). Cycles were administered every 21 days plus granulocyte-colony stimulating growth factors. Patients received prophylaxis with cotrimoxazole and lamivudine (as required).
Results
22 patients were treated in frontline. The median age was 43 years (range: 23-67) and unfavourable risk factors such as erytrocyte sedimentation rate>50 mm/h, ≥3 nodal areas, International Prognostic Score≥3 were present in 68%, 77%, 59% of patients, respectively. All patients completed the planned six courses of therapy without dose reductions or delay. Toxicities were: grade III-IV neutropenia and anemia (9%). Other relevant toxicities were: grade 2 mucocutaneous changes (23%) consisting of skin rash, skin hyperpigmentation and nail alterations, grade 2 transaminases elevation (14%), grade 2 and 3 vomiting (27%) and grade 2 fatigue (18%). We didn’t observe severe or prolonged infections or acute/delayed cardiac or pulmonary toxicities. The overall response rate (ORR) was 100%, complete response (CR) were 91%, partial response (PR) were 9%. In patients with bulky disease, 83% achieved CR at the end of treatment. Positron emission tomography (PET) after 2 and 4 cycles was negative in 68% and 91% patients, respectively. Only 2 patients were in PR at the end of cycle 6 and underwent to consolidation treatment: 1) Radiotherapy (RT); 2) High-dose therapy followed by autologous stem cell transplantation (ASCT), improving PR, then salvage with brentuximab vedotin, reaching CR. At a median follow-up of 31.5 months (range: 4-53), all patients were alive and in continuous CR and the median progression free survival (mPFS) hasn’t been reached.
Conclusion
On a larger series, we confirm the safety and feasibility of ABVDDD-DI, in the context of “real life” clinical practice. This intensified schedule seems to be promising in increasing the efficacy of standard ABVD, in the subset of advanced, high risk HL, in frontline therapy. Our results reinforce the critical role of dose-intensity to achieve CR and probably to reduce the need for salvage therapy followed by ASCT. Probably, the role of RT may be limited to patients with positive PET disease sites, at the end of treatment, as already demonstrated for BEACOPPescalated in the same context (Engert et al, 2012). Finally, even with a longer median follow-up (31.5 months), mPFS hasn’t yet been reached and relevant toxicities haven’t been highlighted.
Session topic: E-poster
Keyword(s): Chemotherapy, Dose intensity, High risk, Hodgkin's lymphoma
Type: Eposter Presentation
Background
The optimal therapeutic upfront strategy in advanced classic HL hasn’t yet been standardized. In recent years, the scientific community has given greater attention to the concept of dose-intensity and several studies demonstrated that intensifying therapy through dose-escalation of drugs and shortening cycle intervals yields best results than standard ABVD. However, the best frontline approach is still debated and the dispute remains between 2 strategies: 1)The “first hit principle” followed by dose reduction in early responders, 2) The “standard dose” followed by the “second hit” in poor responders.
Aims
Based on the promising results of our recent experience (D’Arco et al, 2015) and of a phase II trial of DD-DI ABVD in advanced HL (Russo et al, 2014) we expanded our previous series and updated follow-up to confirm our findings.
Methods
We treated in frontline, 22 consecutive cases of advanced HL with the ABVD DD-DI protocol (Russo et al, 2014), between June 2011 and December 2015. The drugs were given on days 1 and 11, at the doses of standard ABVD except for doxorubicin (escalated to 35 mg/m2, in the first 4 of 6 cycles). Cycles were administered every 21 days plus granulocyte-colony stimulating growth factors. Patients received prophylaxis with cotrimoxazole and lamivudine (as required).
Results
22 patients were treated in frontline. The median age was 43 years (range: 23-67) and unfavourable risk factors such as erytrocyte sedimentation rate>50 mm/h, ≥3 nodal areas, International Prognostic Score≥3 were present in 68%, 77%, 59% of patients, respectively. All patients completed the planned six courses of therapy without dose reductions or delay. Toxicities were: grade III-IV neutropenia and anemia (9%). Other relevant toxicities were: grade 2 mucocutaneous changes (23%) consisting of skin rash, skin hyperpigmentation and nail alterations, grade 2 transaminases elevation (14%), grade 2 and 3 vomiting (27%) and grade 2 fatigue (18%). We didn’t observe severe or prolonged infections or acute/delayed cardiac or pulmonary toxicities. The overall response rate (ORR) was 100%, complete response (CR) were 91%, partial response (PR) were 9%. In patients with bulky disease, 83% achieved CR at the end of treatment. Positron emission tomography (PET) after 2 and 4 cycles was negative in 68% and 91% patients, respectively. Only 2 patients were in PR at the end of cycle 6 and underwent to consolidation treatment: 1) Radiotherapy (RT); 2) High-dose therapy followed by autologous stem cell transplantation (ASCT), improving PR, then salvage with brentuximab vedotin, reaching CR. At a median follow-up of 31.5 months (range: 4-53), all patients were alive and in continuous CR and the median progression free survival (mPFS) hasn’t been reached.
Conclusion
On a larger series, we confirm the safety and feasibility of ABVDDD-DI, in the context of “real life” clinical practice. This intensified schedule seems to be promising in increasing the efficacy of standard ABVD, in the subset of advanced, high risk HL, in frontline therapy. Our results reinforce the critical role of dose-intensity to achieve CR and probably to reduce the need for salvage therapy followed by ASCT. Probably, the role of RT may be limited to patients with positive PET disease sites, at the end of treatment, as already demonstrated for BEACOPPescalated in the same context (Engert et al, 2012). Finally, even with a longer median follow-up (31.5 months), mPFS hasn’t yet been reached and relevant toxicities haven’t been highlighted.
Session topic: E-poster
Keyword(s): Chemotherapy, Dose intensity, High risk, Hodgkin's lymphoma
Abstract: LB2259
Type: Eposter Presentation
Background
The optimal therapeutic upfront strategy in advanced classic HL hasn’t yet been standardized. In recent years, the scientific community has given greater attention to the concept of dose-intensity and several studies demonstrated that intensifying therapy through dose-escalation of drugs and shortening cycle intervals yields best results than standard ABVD. However, the best frontline approach is still debated and the dispute remains between 2 strategies: 1)The “first hit principle” followed by dose reduction in early responders, 2) The “standard dose” followed by the “second hit” in poor responders.
Aims
Based on the promising results of our recent experience (D’Arco et al, 2015) and of a phase II trial of DD-DI ABVD in advanced HL (Russo et al, 2014) we expanded our previous series and updated follow-up to confirm our findings.
Methods
We treated in frontline, 22 consecutive cases of advanced HL with the ABVD DD-DI protocol (Russo et al, 2014), between June 2011 and December 2015. The drugs were given on days 1 and 11, at the doses of standard ABVD except for doxorubicin (escalated to 35 mg/m2, in the first 4 of 6 cycles). Cycles were administered every 21 days plus granulocyte-colony stimulating growth factors. Patients received prophylaxis with cotrimoxazole and lamivudine (as required).
Results
22 patients were treated in frontline. The median age was 43 years (range: 23-67) and unfavourable risk factors such as erytrocyte sedimentation rate>50 mm/h, ≥3 nodal areas, International Prognostic Score≥3 were present in 68%, 77%, 59% of patients, respectively. All patients completed the planned six courses of therapy without dose reductions or delay. Toxicities were: grade III-IV neutropenia and anemia (9%). Other relevant toxicities were: grade 2 mucocutaneous changes (23%) consisting of skin rash, skin hyperpigmentation and nail alterations, grade 2 transaminases elevation (14%), grade 2 and 3 vomiting (27%) and grade 2 fatigue (18%). We didn’t observe severe or prolonged infections or acute/delayed cardiac or pulmonary toxicities. The overall response rate (ORR) was 100%, complete response (CR) were 91%, partial response (PR) were 9%. In patients with bulky disease, 83% achieved CR at the end of treatment. Positron emission tomography (PET) after 2 and 4 cycles was negative in 68% and 91% patients, respectively. Only 2 patients were in PR at the end of cycle 6 and underwent to consolidation treatment: 1) Radiotherapy (RT); 2) High-dose therapy followed by autologous stem cell transplantation (ASCT), improving PR, then salvage with brentuximab vedotin, reaching CR. At a median follow-up of 31.5 months (range: 4-53), all patients were alive and in continuous CR and the median progression free survival (mPFS) hasn’t been reached.
Conclusion
On a larger series, we confirm the safety and feasibility of ABVDDD-DI, in the context of “real life” clinical practice. This intensified schedule seems to be promising in increasing the efficacy of standard ABVD, in the subset of advanced, high risk HL, in frontline therapy. Our results reinforce the critical role of dose-intensity to achieve CR and probably to reduce the need for salvage therapy followed by ASCT. Probably, the role of RT may be limited to patients with positive PET disease sites, at the end of treatment, as already demonstrated for BEACOPPescalated in the same context (Engert et al, 2012). Finally, even with a longer median follow-up (31.5 months), mPFS hasn’t yet been reached and relevant toxicities haven’t been highlighted.
Session topic: E-poster
Keyword(s): Chemotherapy, Dose intensity, High risk, Hodgkin's lymphoma
Type: Eposter Presentation
Background
The optimal therapeutic upfront strategy in advanced classic HL hasn’t yet been standardized. In recent years, the scientific community has given greater attention to the concept of dose-intensity and several studies demonstrated that intensifying therapy through dose-escalation of drugs and shortening cycle intervals yields best results than standard ABVD. However, the best frontline approach is still debated and the dispute remains between 2 strategies: 1)The “first hit principle” followed by dose reduction in early responders, 2) The “standard dose” followed by the “second hit” in poor responders.
Aims
Based on the promising results of our recent experience (D’Arco et al, 2015) and of a phase II trial of DD-DI ABVD in advanced HL (Russo et al, 2014) we expanded our previous series and updated follow-up to confirm our findings.
Methods
We treated in frontline, 22 consecutive cases of advanced HL with the ABVD DD-DI protocol (Russo et al, 2014), between June 2011 and December 2015. The drugs were given on days 1 and 11, at the doses of standard ABVD except for doxorubicin (escalated to 35 mg/m2, in the first 4 of 6 cycles). Cycles were administered every 21 days plus granulocyte-colony stimulating growth factors. Patients received prophylaxis with cotrimoxazole and lamivudine (as required).
Results
22 patients were treated in frontline. The median age was 43 years (range: 23-67) and unfavourable risk factors such as erytrocyte sedimentation rate>50 mm/h, ≥3 nodal areas, International Prognostic Score≥3 were present in 68%, 77%, 59% of patients, respectively. All patients completed the planned six courses of therapy without dose reductions or delay. Toxicities were: grade III-IV neutropenia and anemia (9%). Other relevant toxicities were: grade 2 mucocutaneous changes (23%) consisting of skin rash, skin hyperpigmentation and nail alterations, grade 2 transaminases elevation (14%), grade 2 and 3 vomiting (27%) and grade 2 fatigue (18%). We didn’t observe severe or prolonged infections or acute/delayed cardiac or pulmonary toxicities. The overall response rate (ORR) was 100%, complete response (CR) were 91%, partial response (PR) were 9%. In patients with bulky disease, 83% achieved CR at the end of treatment. Positron emission tomography (PET) after 2 and 4 cycles was negative in 68% and 91% patients, respectively. Only 2 patients were in PR at the end of cycle 6 and underwent to consolidation treatment: 1) Radiotherapy (RT); 2) High-dose therapy followed by autologous stem cell transplantation (ASCT), improving PR, then salvage with brentuximab vedotin, reaching CR. At a median follow-up of 31.5 months (range: 4-53), all patients were alive and in continuous CR and the median progression free survival (mPFS) hasn’t been reached.
Conclusion
On a larger series, we confirm the safety and feasibility of ABVDDD-DI, in the context of “real life” clinical practice. This intensified schedule seems to be promising in increasing the efficacy of standard ABVD, in the subset of advanced, high risk HL, in frontline therapy. Our results reinforce the critical role of dose-intensity to achieve CR and probably to reduce the need for salvage therapy followed by ASCT. Probably, the role of RT may be limited to patients with positive PET disease sites, at the end of treatment, as already demonstrated for BEACOPPescalated in the same context (Engert et al, 2012). Finally, even with a longer median follow-up (31.5 months), mPFS hasn’t yet been reached and relevant toxicities haven’t been highlighted.
Session topic: E-poster
Keyword(s): Chemotherapy, Dose intensity, High risk, Hodgkin's lymphoma
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