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Bendamustine Based Conditioning Regime (BACE-Bendamustine, Cytarabine, Cyclophosphamide and Etoposide) for Patients with Lymphoma Undergoing Autologous Stem Cell Transplant
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
Figure 1. Overall (top) and Progression-free (bottom) survival of patients with SCNSL following autologous cell transplantation with TBC conditioning.
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Figure 2. Overall (top) and Progression-free (bottom) survival of patients with SCNSL according to number of treatment courses prior to autologous cell transplantation.
138 We identified 24 patients between 2008-2014 with systemic B-cell NHL and synchronous CNS involvement transplanted with TBC conditioning. Median follow-up for survivors was 4.3 y. Most patients (75%) had diffuse large B-cell lymphoma; one had mantle cell lymphoma, one had Burkitt lymphoma, two had CLL, and two had follicular lymphoma (Table 1). The most common site of CNS involvement was leptomeningeal disease. Most received RCHOP based systemic therapy (67%), and high-dose methotrexate CNS-directed therapy (63%). 21 of 24 patients were transplanted after first response; 86% were in remission, although 43% received more than 1 line of therapy prior to transplant. The other 3 patients had relapsed and were in second remission at transplant. During follow-up, 5 relapsed and 5 died. Three died from relapsed disease, all with CNS involvement; one died of lung abscess and stroke, and one of MRSA pneumonia. At 3 years, OS was 78%, and PFS was 74% (Figure 1). Of the 12 patients who achieved CR1 with initial treatment and then went to transplant, OS and PFS were 83% and 83% at 3 years (Figure 2). Given historically poor outcomes of this patient population, our data supports autologous transplantation with TBC conditioning in first remission for patients with systemic B-cell NHL and synchronous CNS involvement.
Bendamustine Based Conditioning Regime (BACEBendamustine, Cytarabine, Cyclophosphamide and Etoposide) for Patients with Lymphoma Undergoing Autologous Stem Cell Transplant Neelesh Jain 1, Amrita Chakravarti 2, Nitin Sood 3, Anil Arabandi 4, Kasturi Sengupta 5, Joydeep Chakrabartty 6. 1 apollo Glenagles hospital, kolkata, India; 2 Apollo Gleanagles hospital, kolkata, India; 3 Medanta medi city, Delhi, India; 4 Indo American Hospital, Hyderabad, India; 5 Tata Medical centre, kolkata, India; 6 Haematology and stem cell transplant, AMRI hospitals, kolkata, India Background: Autologous Stem Cell Transplantation (ASCT) is standard of care in relapsed diffuse large B-cell lymphoma (DLBCL) and other lymphoproliferative disorders. Carmustine, etoposide, ARA-C, melphalan (BEAM) and lomustine, ARA-C, cyclophosphamide, etoposide (LACE) are commonly used conditioning regimes. Bendamustine has already been shown to be a feasible part of a modified BeEAM (bendamustine, etoposide, cytarabine, melphalan) ASCT conditioning regimen. In a retrospective multi center analysis LACE is a better tolerated regimen with lesser toxicity, earlier engraftment and comparable survival rates. Here we propose that replacing Lomustine with Bendamustine will increase the efficacy and also be tolerable in these patients needing an autograft Aim: To study the safety and efficacy of bendamustine based conditioning regimen.
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Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
Materials and Methods: 17 patients (12 males and 5 females) of Non Hodgkin’s Lymphoma (NHL) and Hodgkin’s Disease (HD), previously treated with multiple combinations of chemotherapy had been included in the study conducted from June 2012 to May 2014. The conditioning regimes used were R-BACE for B-cell and BACE for T-cell lymphoma. RBACE-regime consist of: Rituximab- 375 mg/m2 on day-6, Bendamustine e 200 mg/m2 on day-6, Etoposide 1000mg/ m2 on day-6, ARA-C 2000 mg/m2 on day-5 and day-4 and Cyclophosphamide 1,800mg/m2 on day-3 to day-1. Except rituximab the rest of the regime is same for T-cell lymphoma. Autologous stem cells were infused on day 0. PET-CT follow up has been done and still going on. Result: Of the 17 patients, twelve were DLBCL, two were having relapsed mantle cell lymphoma, and three were diagnosed as relapsed hodgkin’s disease. Overall fourteen patients were in complete remission and three were in partial remission who underwent autologous stem cell transplant. The median number of CD34 positive cells infused were 3.84 million per kg body weight of patient. Median time taken for myeloid engraftment was 13 days, and for platelet engraftment 19 days from the day of stem cell infusion. Fourteen (82.3%) patients developed neutropenic sepsis during the engraftment period, which was managed adequately with broad spectrum I.V. antibiotics. Eight patients developed MDR (multi drug resistant) klebsiella infections but was managed with appropriate antibiotics. No pulmonary toxicity was seen and mucositis was significantly less than than Melphalan containing regime. All patients are still in remission. Conclusion: BACE as conditioning regime followed by ASCT is feasible and effective in patients with NHL and HD. But the incidence of MDR bacterial infections are very high in India and urgent measures are needed here. Thus, the use of Bendamustine in lymphoma conditioning regimen can be recommended on the basis of its high anti-lymphoma activity with a lower toxicity.
139 BEAM Conditioning Is Well Tolerated and Yields Similar Survival in Obese and Non-Obese Patients with Lymphoma: A Case Against Weight-Based Dose Modifications Christina Fair 1, John Rogosheske 2, Ryan Shanley 3, Veronika Bachanova 3. 1 Fairview Health Services, University of Minnesota, Minneapolis, MN; 2 Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN; 3 University of Minnesota Medical Center, Minneapolis, MN Background: BEAM (carmustine, etoposide, cytarabine, melphalan) is the most common high-dose chemotherapy regimen used in autologous hematopoietic cell transplantation (HCT) for lymphoma. Evidence on chemotherapy dosing in obese patients receiving BEAM is limited. The aim of this study was to compare toxicities and transplant outcomes of obese versus non-obese lymphoma patients treated with BEAM without arbitrary weight-based dose adjustment. Methods: We studied 64 consecutive patients uniformly treated with BEAM (carmustine 300 mg/m2 IV day -6, etoposide 100 mg/m2 IV twice daily days -5 to -2, cytarabine 100 mg/m2 IV twice daily days -5 to -2, melphalan 140 mg/m2 IV once day -1) followed by autologous HCT. BEAM dose was calculated using body surface area based on actual body weight (BW). Patients were discharged on day +1 post-HCT, started G-CSF on day +5, and were followed daily as outpatients until engraftment. We compared transplant
Table Outcomes of obese versus non-obese patients with lymphoma after BEAM without weight adjustment followed by autologous HCT Obese Readmission rate (95% CI) TPN (95% CI) Bacteremia density through day 100 Events/100 patient days (95% CI) Median days to ANC recovery (IQR) Median days to platelet 20K (IQR) 1-year PFS (95% CI) 1-year relapse (95% CI)
Non-obese
P
60% (41-77) 65% (46-80) 0.80 27% (12-46) 21% (7-34) 0.77 0.41 (0.21-0.72) 0.48 (0.28-0.78) 0.71
11 (10-11)
10 (10-11)
0.25
19 (17-21)
18.5 (16-21)
0.12
79% (58-90) 18% (6-32)
63% (44-77) 33% (17-49)
0.24 0.19
outcomes between obese patients (n¼30; ideal BW >125%; median body mass index (BMI) 32; range 24-46) and nonobese patients (n¼34; ideal BW<125%; median BMI 25; range18-29). Results: Median age was 59 years (range 29-74). All patients had non-Hodgkin lymphoma, and two-thirds were in complete remission. Performance status and co-morbidities were similar between weight groups. Median follow-up was 1 year (range 3-25 months). Nearly two-thirds of all patients in both groups were readmitted with complications, with a quarter requiring total parenteral nutrition (Table). Median days in the hospital for obese and non-obese patients was 13.5 (interquartile range 11-19) and 12 (7-14) days (p¼0.07). Bacteremia density during the first 100 days and neutrophil/platelet engraftment were similar for the two groups (Table). One obese patient died from complications. Overall survival at 1 year was 86% (95% CI 68-95) for obese patients and 70% (95% CI 49-84; p¼0.36) for non-obese patients. One-year progression-free survival and relapse rate were similar (Table). Conclusion: Our results suggest that BEAM chemotherapy used without drug dose-modifications for obesity yields comparable survival and toxicity in obese and non-obese lymphoma patients undergoing autologous HCT. Future investigations should study strategies to reduce morbidity and re-admissions in all patients treated with BEAM.
140 Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma Utilizing a Reduced Fixed Dose of Plerixafor and a Unique Mobilization Algorithm is Feasible and Maximizes Day 1 Collection Yield Omotayo Fasan 1, Eric Chow 2, Saad Usmani 1, Jigar S. Trivedi 2, Dragos Plesca 2, Margaret Croom 2, Carlos G. Lee 3, Samantha M. Carter 3, Manisha Bhutani 4, Belinda Avalos 1, Edward A. Copelan 5. 1 Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC; 2 Pharmacy, Levine Cancer Institute, Charlotte, NC; 3 Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC; 4 Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC, Andorra; 5 Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC Background: Peripheral blood progenitor cell (PBPC) mobilization and collection is an important first step in autologous hematopoietic cell transplantation. The ideal mobilization strategy should maximize day 1 collection yield. Mobilization with filgrastim and plerixafor can achieve this, however the high cost of plerixafor limits its widespread utilization.
Figure 1. Overall (top) and Progression-free (bottom) survival of patients with SCNSL following autologous cell transplantation with TBC conditioning.
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Figure 2. Overall (top) and Progression-free (bottom) survival of patients with SCNSL according to number of treatment courses prior to autologous cell transplantation.
138 We identified 24 patients between 2008-2014 with systemic B-cell NHL and synchronous CNS involvement transplanted with TBC conditioning. Median follow-up for survivors was 4.3 y. Most patients (75%) had diffuse large B-cell lymphoma; one had mantle cell lymphoma, one had Burkitt lymphoma, two had CLL, and two had follicular lymphoma (Table 1). The most common site of CNS involvement was leptomeningeal disease. Most received RCHOP based systemic therapy (67%), and high-dose methotrexate CNS-directed therapy (63%). 21 of 24 patients were transplanted after first response; 86% were in remission, although 43% received more than 1 line of therapy prior to transplant. The other 3 patients had relapsed and were in second remission at transplant. During follow-up, 5 relapsed and 5 died. Three died from relapsed disease, all with CNS involvement; one died of lung abscess and stroke, and one of MRSA pneumonia. At 3 years, OS was 78%, and PFS was 74% (Figure 1). Of the 12 patients who achieved CR1 with initial treatment and then went to transplant, OS and PFS were 83% and 83% at 3 years (Figure 2). Given historically poor outcomes of this patient population, our data supports autologous transplantation with TBC conditioning in first remission for patients with systemic B-cell NHL and synchronous CNS involvement.
Bendamustine Based Conditioning Regime (BACEBendamustine, Cytarabine, Cyclophosphamide and Etoposide) for Patients with Lymphoma Undergoing Autologous Stem Cell Transplant Neelesh Jain 1, Amrita Chakravarti 2, Nitin Sood 3, Anil Arabandi 4, Kasturi Sengupta 5, Joydeep Chakrabartty 6. 1 apollo Glenagles hospital, kolkata, India; 2 Apollo Gleanagles hospital, kolkata, India; 3 Medanta medi city, Delhi, India; 4 Indo American Hospital, Hyderabad, India; 5 Tata Medical centre, kolkata, India; 6 Haematology and stem cell transplant, AMRI hospitals, kolkata, India Background: Autologous Stem Cell Transplantation (ASCT) is standard of care in relapsed diffuse large B-cell lymphoma (DLBCL) and other lymphoproliferative disorders. Carmustine, etoposide, ARA-C, melphalan (BEAM) and lomustine, ARA-C, cyclophosphamide, etoposide (LACE) are commonly used conditioning regimes. Bendamustine has already been shown to be a feasible part of a modified BeEAM (bendamustine, etoposide, cytarabine, melphalan) ASCT conditioning regimen. In a retrospective multi center analysis LACE is a better tolerated regimen with lesser toxicity, earlier engraftment and comparable survival rates. Here we propose that replacing Lomustine with Bendamustine will increase the efficacy and also be tolerable in these patients needing an autograft Aim: To study the safety and efficacy of bendamustine based conditioning regimen.
S122
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
Materials and Methods: 17 patients (12 males and 5 females) of Non Hodgkin’s Lymphoma (NHL) and Hodgkin’s Disease (HD), previously treated with multiple combinations of chemotherapy had been included in the study conducted from June 2012 to May 2014. The conditioning regimes used were R-BACE for B-cell and BACE for T-cell lymphoma. RBACE-regime consist of: Rituximab- 375 mg/m2 on day-6, Bendamustine e 200 mg/m2 on day-6, Etoposide 1000mg/ m2 on day-6, ARA-C 2000 mg/m2 on day-5 and day-4 and Cyclophosphamide 1,800mg/m2 on day-3 to day-1. Except rituximab the rest of the regime is same for T-cell lymphoma. Autologous stem cells were infused on day 0. PET-CT follow up has been done and still going on. Result: Of the 17 patients, twelve were DLBCL, two were having relapsed mantle cell lymphoma, and three were diagnosed as relapsed hodgkin’s disease. Overall fourteen patients were in complete remission and three were in partial remission who underwent autologous stem cell transplant. The median number of CD34 positive cells infused were 3.84 million per kg body weight of patient. Median time taken for myeloid engraftment was 13 days, and for platelet engraftment 19 days from the day of stem cell infusion. Fourteen (82.3%) patients developed neutropenic sepsis during the engraftment period, which was managed adequately with broad spectrum I.V. antibiotics. Eight patients developed MDR (multi drug resistant) klebsiella infections but was managed with appropriate antibiotics. No pulmonary toxicity was seen and mucositis was significantly less than than Melphalan containing regime. All patients are still in remission. Conclusion: BACE as conditioning regime followed by ASCT is feasible and effective in patients with NHL and HD. But the incidence of MDR bacterial infections are very high in India and urgent measures are needed here. Thus, the use of Bendamustine in lymphoma conditioning regimen can be recommended on the basis of its high anti-lymphoma activity with a lower toxicity.
139 BEAM Conditioning Is Well Tolerated and Yields Similar Survival in Obese and Non-Obese Patients with Lymphoma: A Case Against Weight-Based Dose Modifications Christina Fair 1, John Rogosheske 2, Ryan Shanley 3, Veronika Bachanova 3. 1 Fairview Health Services, University of Minnesota, Minneapolis, MN; 2 Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN; 3 University of Minnesota Medical Center, Minneapolis, MN Background: BEAM (carmustine, etoposide, cytarabine, melphalan) is the most common high-dose chemotherapy regimen used in autologous hematopoietic cell transplantation (HCT) for lymphoma. Evidence on chemotherapy dosing in obese patients receiving BEAM is limited. The aim of this study was to compare toxicities and transplant outcomes of obese versus non-obese lymphoma patients treated with BEAM without arbitrary weight-based dose adjustment. Methods: We studied 64 consecutive patients uniformly treated with BEAM (carmustine 300 mg/m2 IV day -6, etoposide 100 mg/m2 IV twice daily days -5 to -2, cytarabine 100 mg/m2 IV twice daily days -5 to -2, melphalan 140 mg/m2 IV once day -1) followed by autologous HCT. BEAM dose was calculated using body surface area based on actual body weight (BW). Patients were discharged on day +1 post-HCT, started G-CSF on day +5, and were followed daily as outpatients until engraftment. We compared transplant
Table Outcomes of obese versus non-obese patients with lymphoma after BEAM without weight adjustment followed by autologous HCT Obese Readmission rate (95% CI) TPN (95% CI) Bacteremia density through day 100 Events/100 patient days (95% CI) Median days to ANC recovery (IQR) Median days to platelet 20K (IQR) 1-year PFS (95% CI) 1-year relapse (95% CI)
Non-obese
P
60% (41-77) 65% (46-80) 0.80 27% (12-46) 21% (7-34) 0.77 0.41 (0.21-0.72) 0.48 (0.28-0.78) 0.71
11 (10-11)
10 (10-11)
0.25
19 (17-21)
18.5 (16-21)
0.12
79% (58-90) 18% (6-32)
63% (44-77) 33% (17-49)
0.24 0.19
outcomes between obese patients (n¼30; ideal BW >125%; median body mass index (BMI) 32; range 24-46) and nonobese patients (n¼34; ideal BW<125%; median BMI 25; range18-29). Results: Median age was 59 years (range 29-74). All patients had non-Hodgkin lymphoma, and two-thirds were in complete remission. Performance status and co-morbidities were similar between weight groups. Median follow-up was 1 year (range 3-25 months). Nearly two-thirds of all patients in both groups were readmitted with complications, with a quarter requiring total parenteral nutrition (Table). Median days in the hospital for obese and non-obese patients was 13.5 (interquartile range 11-19) and 12 (7-14) days (p¼0.07). Bacteremia density during the first 100 days and neutrophil/platelet engraftment were similar for the two groups (Table). One obese patient died from complications. Overall survival at 1 year was 86% (95% CI 68-95) for obese patients and 70% (95% CI 49-84; p¼0.36) for non-obese patients. One-year progression-free survival and relapse rate were similar (Table). Conclusion: Our results suggest that BEAM chemotherapy used without drug dose-modifications for obesity yields comparable survival and toxicity in obese and non-obese lymphoma patients undergoing autologous HCT. Future investigations should study strategies to reduce morbidity and re-admissions in all patients treated with BEAM.
140 Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma Utilizing a Reduced Fixed Dose of Plerixafor and a Unique Mobilization Algorithm is Feasible and Maximizes Day 1 Collection Yield Omotayo Fasan 1, Eric Chow 2, Saad Usmani 1, Jigar S. Trivedi 2, Dragos Plesca 2, Margaret Croom 2, Carlos G. Lee 3, Samantha M. Carter 3, Manisha Bhutani 4, Belinda Avalos 1, Edward A. Copelan 5. 1 Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC; 2 Pharmacy, Levine Cancer Institute, Charlotte, NC; 3 Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC; 4 Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC, Andorra; 5 Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC Background: Peripheral blood progenitor cell (PBPC) mobilization and collection is an important first step in autologous hematopoietic cell transplantation. The ideal mobilization strategy should maximize day 1 collection yield. Mobilization with filgrastim and plerixafor can achieve this, however the high cost of plerixafor limits its widespread utilization.