A SINGLE CENTRE EXPERIENCE OF DPACE-BASED THERAPY WITH LENALIDOMIDE OR THALIDOMIDE +/- BORTEZOMIB PRIOR TO AUTOLOGOUS TRANSPLANT IN MYELOMA
(Abstract release date: 05/19/16)
EHA Library. Parker T. 06/09/16; 134895; PB1995
Dr. Tracey Parker
Contributions
Contributions
Abstract
Abstract: PB1995
Type: Publication Only
Background
DPACE (infusional Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide and oral Dexamethasone) with Thalidomide and Bortezomib is used within the Arkansas Total Therapy Regimen for myeloma. We have used DPACE-based therapy for high-risk and poorly responsive myeloma prior to autologous transplant (ASCT).
Aims
To establish the toxicity and efficacy of DPACE based chemotherapy with a combination of thalidomide or lenalidomide and/or bortezomib as a stand alone therapy or prior to consolidation with autologous stem cell transplant in high risk or poorly responsive myeloma.
Methods
We conducted a retrospective review of 22 patients treated at a single centre with DPACE-based therapy between 2010-2015 incuding two who received DPACE-based therapy as two separate treatment lines. Overall survival and time to next treatment from commencement of DPACE-based therapy were estimated using a Kaplan-Meier method and the impact of categorical variables assessed using a log rank analysis. Median follow-up was 2.1 years.
Results
PS was 0 (72.7%) or 1 (27.3%). ISS at commencement of DPACE was I (27.3%), II (22.7%) and III (36.4%). 15 of 22 patients had FISH performed prior to DPACE of which 40% had 2 or more adverse abnormalities (gain 1q, loss 1p, loss 17p, t(4;14), t(14;16), t(14;20)). Patients received DPACE with an Immunomodulatory agent (Lenalidomide 62.5% or Thalidomide 37.5%) and 66% received Bortezomib. DPACE-based therapy was used as primary therapy in 4/24 (16.6%) for and as salvage for suboptimal response in 20/24 (83.3%). Two cycles were given in 22/24 (92%).Patients received a median of 2 units of red cells per cycle (range 0-8 in cycle 1, 0-12 in cycle 2). Median platelets transfusions equalled 1.5 (0-6) in cycle 1 and 3.5 (0-9) in cycle 2. All patients experienced grade 4 neutropenia with median duration of 6 days in cycle 1 and 5 days in cycle 2. Grade 3-4 sepsis occurred in 9/24 (37.5%) in cycle 1 and 7/22 (31.8%) in cycle 2. All planned patients harvested successfully.From start of DPACE-based therapy, median OS was 23.3 months. Median TTNT was 12.6 months.Treatment-related mortality was 1/24 (4.1%) due to sepsis. Following DPACE-based therapy, 12/24 (50.0%) achieved CR or VGPR. 15/24 (62.5%) were consolidated with transplant (one allogeneic). Consolidation with ASCT demonstrated a clearly superior OS (77.1% vs 0% at 2 years, p<0.001) and improved TTNT (median 33.1 vs 4.3 months, p=0.007). Lenalidomide did not impact on toxicity or response rates. There were no reported second primary malignancies in any patients.
Conclusion
DPACE-based therapy is an effective induction or salvage therapy prior to ASCT in high risk or poorly responsive myeloma. Toxicity is manageable and stem cell harvest is achievable. Time to next treatment and overall survival is significantly longer in those consolidated with stem cell transplant indicating that there is limited value in using PACE-based chemotherapy without stem cell transplant. Initial data does not indicate a difference between Lenalidomide or Thalidomide in toxicity, response rates or survival although longer follow-up is warranted to investigate this further.
Session topic: E-poster
Keyword(s): Bortezomib, Immunomodulatory thalidomide analog, Myeloma
Type: Publication Only
Background
DPACE (infusional Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide and oral Dexamethasone) with Thalidomide and Bortezomib is used within the Arkansas Total Therapy Regimen for myeloma. We have used DPACE-based therapy for high-risk and poorly responsive myeloma prior to autologous transplant (ASCT).
Aims
To establish the toxicity and efficacy of DPACE based chemotherapy with a combination of thalidomide or lenalidomide and/or bortezomib as a stand alone therapy or prior to consolidation with autologous stem cell transplant in high risk or poorly responsive myeloma.
Methods
We conducted a retrospective review of 22 patients treated at a single centre with DPACE-based therapy between 2010-2015 incuding two who received DPACE-based therapy as two separate treatment lines. Overall survival and time to next treatment from commencement of DPACE-based therapy were estimated using a Kaplan-Meier method and the impact of categorical variables assessed using a log rank analysis. Median follow-up was 2.1 years.
Results
PS was 0 (72.7%) or 1 (27.3%). ISS at commencement of DPACE was I (27.3%), II (22.7%) and III (36.4%). 15 of 22 patients had FISH performed prior to DPACE of which 40% had 2 or more adverse abnormalities (gain 1q, loss 1p, loss 17p, t(4;14), t(14;16), t(14;20)). Patients received DPACE with an Immunomodulatory agent (Lenalidomide 62.5% or Thalidomide 37.5%) and 66% received Bortezomib. DPACE-based therapy was used as primary therapy in 4/24 (16.6%) for and as salvage for suboptimal response in 20/24 (83.3%). Two cycles were given in 22/24 (92%).Patients received a median of 2 units of red cells per cycle (range 0-8 in cycle 1, 0-12 in cycle 2). Median platelets transfusions equalled 1.5 (0-6) in cycle 1 and 3.5 (0-9) in cycle 2. All patients experienced grade 4 neutropenia with median duration of 6 days in cycle 1 and 5 days in cycle 2. Grade 3-4 sepsis occurred in 9/24 (37.5%) in cycle 1 and 7/22 (31.8%) in cycle 2. All planned patients harvested successfully.From start of DPACE-based therapy, median OS was 23.3 months. Median TTNT was 12.6 months.Treatment-related mortality was 1/24 (4.1%) due to sepsis. Following DPACE-based therapy, 12/24 (50.0%) achieved CR or VGPR. 15/24 (62.5%) were consolidated with transplant (one allogeneic). Consolidation with ASCT demonstrated a clearly superior OS (77.1% vs 0% at 2 years, p<0.001) and improved TTNT (median 33.1 vs 4.3 months, p=0.007). Lenalidomide did not impact on toxicity or response rates. There were no reported second primary malignancies in any patients.
Conclusion
DPACE-based therapy is an effective induction or salvage therapy prior to ASCT in high risk or poorly responsive myeloma. Toxicity is manageable and stem cell harvest is achievable. Time to next treatment and overall survival is significantly longer in those consolidated with stem cell transplant indicating that there is limited value in using PACE-based chemotherapy without stem cell transplant. Initial data does not indicate a difference between Lenalidomide or Thalidomide in toxicity, response rates or survival although longer follow-up is warranted to investigate this further.
Session topic: E-poster
Keyword(s): Bortezomib, Immunomodulatory thalidomide analog, Myeloma
Abstract: PB1995
Type: Publication Only
Background
DPACE (infusional Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide and oral Dexamethasone) with Thalidomide and Bortezomib is used within the Arkansas Total Therapy Regimen for myeloma. We have used DPACE-based therapy for high-risk and poorly responsive myeloma prior to autologous transplant (ASCT).
Aims
To establish the toxicity and efficacy of DPACE based chemotherapy with a combination of thalidomide or lenalidomide and/or bortezomib as a stand alone therapy or prior to consolidation with autologous stem cell transplant in high risk or poorly responsive myeloma.
Methods
We conducted a retrospective review of 22 patients treated at a single centre with DPACE-based therapy between 2010-2015 incuding two who received DPACE-based therapy as two separate treatment lines. Overall survival and time to next treatment from commencement of DPACE-based therapy were estimated using a Kaplan-Meier method and the impact of categorical variables assessed using a log rank analysis. Median follow-up was 2.1 years.
Results
PS was 0 (72.7%) or 1 (27.3%). ISS at commencement of DPACE was I (27.3%), II (22.7%) and III (36.4%). 15 of 22 patients had FISH performed prior to DPACE of which 40% had 2 or more adverse abnormalities (gain 1q, loss 1p, loss 17p, t(4;14), t(14;16), t(14;20)). Patients received DPACE with an Immunomodulatory agent (Lenalidomide 62.5% or Thalidomide 37.5%) and 66% received Bortezomib. DPACE-based therapy was used as primary therapy in 4/24 (16.6%) for and as salvage for suboptimal response in 20/24 (83.3%). Two cycles were given in 22/24 (92%).Patients received a median of 2 units of red cells per cycle (range 0-8 in cycle 1, 0-12 in cycle 2). Median platelets transfusions equalled 1.5 (0-6) in cycle 1 and 3.5 (0-9) in cycle 2. All patients experienced grade 4 neutropenia with median duration of 6 days in cycle 1 and 5 days in cycle 2. Grade 3-4 sepsis occurred in 9/24 (37.5%) in cycle 1 and 7/22 (31.8%) in cycle 2. All planned patients harvested successfully.From start of DPACE-based therapy, median OS was 23.3 months. Median TTNT was 12.6 months.Treatment-related mortality was 1/24 (4.1%) due to sepsis. Following DPACE-based therapy, 12/24 (50.0%) achieved CR or VGPR. 15/24 (62.5%) were consolidated with transplant (one allogeneic). Consolidation with ASCT demonstrated a clearly superior OS (77.1% vs 0% at 2 years, p<0.001) and improved TTNT (median 33.1 vs 4.3 months, p=0.007). Lenalidomide did not impact on toxicity or response rates. There were no reported second primary malignancies in any patients.
Conclusion
DPACE-based therapy is an effective induction or salvage therapy prior to ASCT in high risk or poorly responsive myeloma. Toxicity is manageable and stem cell harvest is achievable. Time to next treatment and overall survival is significantly longer in those consolidated with stem cell transplant indicating that there is limited value in using PACE-based chemotherapy without stem cell transplant. Initial data does not indicate a difference between Lenalidomide or Thalidomide in toxicity, response rates or survival although longer follow-up is warranted to investigate this further.
Session topic: E-poster
Keyword(s): Bortezomib, Immunomodulatory thalidomide analog, Myeloma
Type: Publication Only
Background
DPACE (infusional Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide and oral Dexamethasone) with Thalidomide and Bortezomib is used within the Arkansas Total Therapy Regimen for myeloma. We have used DPACE-based therapy for high-risk and poorly responsive myeloma prior to autologous transplant (ASCT).
Aims
To establish the toxicity and efficacy of DPACE based chemotherapy with a combination of thalidomide or lenalidomide and/or bortezomib as a stand alone therapy or prior to consolidation with autologous stem cell transplant in high risk or poorly responsive myeloma.
Methods
We conducted a retrospective review of 22 patients treated at a single centre with DPACE-based therapy between 2010-2015 incuding two who received DPACE-based therapy as two separate treatment lines. Overall survival and time to next treatment from commencement of DPACE-based therapy were estimated using a Kaplan-Meier method and the impact of categorical variables assessed using a log rank analysis. Median follow-up was 2.1 years.
Results
PS was 0 (72.7%) or 1 (27.3%). ISS at commencement of DPACE was I (27.3%), II (22.7%) and III (36.4%). 15 of 22 patients had FISH performed prior to DPACE of which 40% had 2 or more adverse abnormalities (gain 1q, loss 1p, loss 17p, t(4;14), t(14;16), t(14;20)). Patients received DPACE with an Immunomodulatory agent (Lenalidomide 62.5% or Thalidomide 37.5%) and 66% received Bortezomib. DPACE-based therapy was used as primary therapy in 4/24 (16.6%) for and as salvage for suboptimal response in 20/24 (83.3%). Two cycles were given in 22/24 (92%).Patients received a median of 2 units of red cells per cycle (range 0-8 in cycle 1, 0-12 in cycle 2). Median platelets transfusions equalled 1.5 (0-6) in cycle 1 and 3.5 (0-9) in cycle 2. All patients experienced grade 4 neutropenia with median duration of 6 days in cycle 1 and 5 days in cycle 2. Grade 3-4 sepsis occurred in 9/24 (37.5%) in cycle 1 and 7/22 (31.8%) in cycle 2. All planned patients harvested successfully.From start of DPACE-based therapy, median OS was 23.3 months. Median TTNT was 12.6 months.Treatment-related mortality was 1/24 (4.1%) due to sepsis. Following DPACE-based therapy, 12/24 (50.0%) achieved CR or VGPR. 15/24 (62.5%) were consolidated with transplant (one allogeneic). Consolidation with ASCT demonstrated a clearly superior OS (77.1% vs 0% at 2 years, p<0.001) and improved TTNT (median 33.1 vs 4.3 months, p=0.007). Lenalidomide did not impact on toxicity or response rates. There were no reported second primary malignancies in any patients.
Conclusion
DPACE-based therapy is an effective induction or salvage therapy prior to ASCT in high risk or poorly responsive myeloma. Toxicity is manageable and stem cell harvest is achievable. Time to next treatment and overall survival is significantly longer in those consolidated with stem cell transplant indicating that there is limited value in using PACE-based chemotherapy without stem cell transplant. Initial data does not indicate a difference between Lenalidomide or Thalidomide in toxicity, response rates or survival although longer follow-up is warranted to investigate this further.
Session topic: E-poster
Keyword(s): Bortezomib, Immunomodulatory thalidomide analog, Myeloma
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