- Email: [email protected]
Single-Center Experience of a Triple Drug Prophylaxis Regimen for Sinusoidal Obstructive Syndrome (SOS) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
S286
Abstracts / Biol Blood Marrow Transplant 25 (2019) S100 S289
This is a quality improvement project to help decrease the admission rate for febrile neutropenia in the hematological malignancy population. The focus will be on utilizing a checklist to help facilitate a rapid admission/discharge process. The checklist is comprised of high risk features that providers should assess all patients for. If patients have 2 or more of the risk factors they should remain inpatient per current standard of care otherwise patients should be discharged within 48 hours. Hematological malignancy patients admitted from October 2017- January 31st 2019 will be reviewed and compared to historical data on readmission rates at our institution. Preliminary data has shown a decrease in the length of admission (3 vs. 5 days) between patients where the protocol was utilized versus historical data. Reasons patients have not discharged within 48 hours has included clinician judgment, positive cultures and severe neutropenia. Data collection is ongoing and updated results will be presented at the meeting in February 2019.
418 Relapse Rates in Patients Receiving Azithromycin for the Treatment of Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplant Jade L. Kutzke PharmD1, Jodi L Taraba PharmD2, Julianna A Merten PharmD3, Mithun V. Shah MD, PhD4, Shahrukh K. Hashmi MD, MPH4, Mrinal M. Patnaik MBBS4, Mark R. Litzow MD4, William J. Hogan MD4, Hassan B. Alkhateeb MD4. 1 Pharmacy, Mayo Clinic Hospital, Rochester, MN; 2 Mayo Clinic Hospital, Rochester, MN; 3 Department of Pharmacy Services, Mayo Clinic, Rochester, MN; 4 Division of Hematology, Mayo Clinic, Rochester, MN Introduction: The FDA issued a warning on the increased risk of hematologic relapse based on the ALLOZITHRO trial, recommending azithromycin not be used long-term in patients that have undergone allogenic hematopoietic stem cell transplant (HSCT). In the ALLOZITHRO trial, azithromycin was started at the time of the conditioning regimen for prophylaxis of bronchiolitis obliterans (BO); however, at our site and many others across the country, azithromycin is initiated after BO. Objective: The goal of this study was to evaluate if azithromycin used in treatment of BO is associated with an increase in the rate of relapse. Methods: IRB approval was obtained prior to review of the electronic medical record and the Mayo Clinic HSCT database. Adult patients who received an allogeneic HSCT from January 2008 August 2018 for a malignant disease and received 2 weeks of azithromycin were included in this study. Patients were excluded if they received <2 weeks of azithromycin therapy, received azithromycin prior to 100 days post-HCST, relapsed prior to the initiation of azithromycin, or never achieved disease remission prior to starting azithromycin. Data collected via retrospective review included patient demographics, azithromycin regimen and duration, death, relapse, and date of last follow-up. Results: Of 466 adult patients who received an allogenic HSCT at Mayo Clinic Hospital-Rochester for malignant disease, 185 patients received azithromycin. Of 185 patients who received azithromycin, 87 were excluded: declined research participation (n = 7), received <2 weeks of azithromycin therapy (n = 65), azithromycin initiated prior to 100 days post-HCST (n = 11), relapse prior to the initiation of azithromycin (n = 2), or never achieved disease remission (n = 2). We identified 98 patients who met our inclusion/exclusion criteria. The median age was 56 years (23-74). The majority of patients received azithromycin 250 or 500 mg three times weekly: 500 mg three times weekly (n = 51), 250 three times weekly (n = 40). The
median time to azithromycin initiation was 16.6 months (IQR 9.4-26). The median duration of azithromycin therapy was 33.9 months (IQR 1.4-116.4). Death occurred in 2 patients (2%) and was not related to relapse. Two patients (2%) relapsed a median of 28 months (IQR 7.2-49) after transplant. The median time to relapse after azithromycin initiation was 10.4 months (IQR 2.5-18.2). The two patients who relapsed were at high risk for relapse as one had FLT3 ITD mutation in CR1 without FLT3 inhibitor treatment, and the other had heavily pretreated multiple myeloma. Both achieved remission and are alive at the time of last follow up. The median overall survival for this cohort from the start of azithromycin was not reached. Conclusion: The use of azithromycin as treatment for BO was not associated with a high incidence of disease relapse in this study. Further research is needed to confirm our findings.
419 Single-Center Experience of a Triple Drug Prophylaxis Regimen for Sinusoidal Obstructive Syndrome (SOS) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Samrah Ahmad PharmD1, Ruthee-Lu Bayer MD2, Mukesh Tiwari MBBS3. 1 Pharmacy, North Shore University Hospital, Manhasset, NY; 2 Hematology/Oncology, North Shore University Hospital, Northwell Health, Lake Success, NY; 3 Oncology, Northwell Health, Lake Success, NY Purpose: Hepatic veno-occlusive disease (VOD) or SOS is a serious and potentially fatal complication of HSCT. Due to the limited amount of data regarding prophylactic agents for VOD, the goal of this study is to determine the efficacy of the triple prophylactic regimen utilized at North Shore University Hospital (NSUH), in preventing VOD until engraftment in patients undergoing allogeneic HSCT. Methods: This retrospective cohort study included patients 18 years and older admitted to NSUH for an allogeneic HSCT during 2015-18. Patients that had known hypersensitivity to any of the prophylactic agents and/ or who were hemodynamically unstable within 24 hours of starting VOD prophylaxis were excluded. All patients received the standard regimen of continuous infusion heparin at a dose of 100 units/kg/day, Ursodiol 300 mg by mouth twice a day, and glutamine 15 gram in two divided doses. Patients were monitored closely for any weight changes and aggressive management with diuretics was utilized to avoid fluid overload and hepatic congestion. The primary outcome measure was to achieve VOD-free survival at engraftment and secondary outcomes was any adverse effects due to the regimen. Results: The study included 109 patients, 61 male, 48 female, average age of 54 years (range 20-75 years) and average weight of 81.2 kg (range 42.8-155.5kg). The patients were in the hospital for an average of 31 days (range 20-93; median 28 days). None of the patients experienced fulminant SOS/VOD as per European Society for Blood and Marrow Transplantation (EBMT) criteria. Ultrasounds were done in 3 patients, with no abnormalities suggestive of VOD. Prior to engraftment 1 patient had ascites, 2 painful hepatomegaly, 1 right upper quadrant pain, and 23 (21.1%) concurrent organ dysfunction requiring supportive care such as oxygen supplementation (5.5%) and/or Intravenous fluids (6.4%). Patient’s weight, bilirubin, AST, ALT, and serum creatinine were monitored at baseline and daily for any abnormalities. Patients experienced an average weight increase of 4% (0-7%), 11 patients (10%) had a bilirubin of greater then 2mg/dl but had no other criteria for SOS. Majority of the patients returned to their baseline (95%). Only 3 patients required discontinuation of heparin, no other
Abstracts / Biol Blood Marrow Transplant 25 (2019) S100 S289
S287
adverse effects were reported. All patients received diuretics for an average of 7 days (range 1-42 days) and mean dose was 46mg/day (range 20- 160mg). Of note one patient died before engraftment with possible late onset VOD, patient had elevated bilirubin and weight gain of 18.6% with trace ascites. Patient had received Inotuzumab Ozogamicin as salvage treatment prior to HSCT. Conclusion: No instances of classical SOS/VOD were reported in the 109 patients undergoing allogeneic HSCT receiving the triple therapy regimen. One patient had possible late onset VOD. The data suggests an efficacious role of the triple prophylactic drug combination in this setting.
Results: The percent concentration at various time points compared to time zero, is presented in Table 1. The percent concentration after 24 hr. of 2 mg/ml CE melphalan in an IV bag was 93.77% at RT, and 95.87% under refrigeration. The percent concentration of 5 mg/ml CE melphalan solution in a glass vials at 24 hr. was 99.44% at RT and 99.84 % under refrigeration. Conclusion: The results indicate that both 2 mg/ml CE melphalan in IV bags, and 5 mg/ml in glass vials are both stable at RT and under refrigeration for 24 hr. after preparation.
420
Timeline from Referral to Admission for CAR-T Infusion: A Single Institution Experience in an Academic Medical Center Zahra Mahmoudjafari PharmD, BCOP1, Caroline Strohm BSN, RN, OCN2, Clint L. Divine MBA, MSM3, Crissy Morrison BSN, RN4, Erin Winters RN, BSN, BMTCN, BMT5, Joseph McGuirk DO6. 1 Department of Pharmacy, University of Kansas Health System, Westwood, KS; 2 The University of Kansas Cancer Center, Westwood, KS; 3 Blood & Marrow Transplantation, Division of Hematological Malignancies & Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS; 4 University of Kansas Cancer Center, Kansas City, KS; 5 University of Kansas Hospital, Westwood, KS; 6 Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS
Stability of Captisol-Enabled Melphalan (Evomela) in 0.9% Sodium Chloride Solution in IV Bags and Glass Vials at Room Temperature and Refrigeration Jitesh D. Kawedia PharmD, PhD1, Sumankalai Ramachandran PhD2, Alison M. Gulbis PharmD1, Mark Titus PhD2, Qaiser Bashir MD3, Muzaffar H. Qazilbash MD3, Richard E. Champlin MD3, Stefan O. Ciurea MD3. 1 Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX; 2 Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; 3 Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Melphalan is an alkylating agent, which is used in intensive treatment of hematological malignancies and solid tumors. The older melphalan formulation (Alkeran) has very limited (<60 minutes) stability, which can significantly affect pharmacy operations and planned patient care. CaptisolEnabled (CE) melphalan (Evomela) is a new formulation with increased stability (4 hr. at room temperature (RT)). In this study, we have determined the stability of 2 mg/ml CE melphalan solution in IV bags and 5 mg/ml reconstituted solution in glass vials at RT and under refrigeration (4°C). Extended stability will allow time for pharmacy to prepare and distribute the IV bags for patients receiving melphalan on standard of care, ongoing studies, and for potential new studies, which would aim to investigate the benefits of prolonged infusion of melphalan. Methods: Lyophilized CE melphalan was reconstituted to 5mg/ ml with 0.9% sodium chloride (in glass vials), diluted to 2 mg/ml with 0.9% sodium chloride, in IV (PVC) bags. They were then stored at RT (23°C) and under refrigeration. Aliquots (1ml) were removed at 0, 2, 4, 6, 8, 12 and 24hr. after preparation of 2mg/ml IV bags and the concentration was analyzed by using a validated high performance liquid chromatography method. Since 5 mg/ml reconstituted vials were previously found to be stable for 24 hr., we determined its stability after 24 hr. at RT and under refrigeration. The 2 mg/ml or 5 mg/ml CE melphalan was considered stable if the concentration at a given time-point was greater than 90% of the initial concentration at time zero.
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Introduction: Administration of chimeric antigen receptor therapy (CAR-T) requires the coordination of a multi-disciplinary team including physicians, nurses, pharmacists, apheresis and financial leaders. With the commercial approval of tisagenlecleucel and axicabtagene ciloleucel, centers were challenged with securing financial authorization, completing leukapheresis and lymphodepleting chemotherapy in a timely manner prior to cellular infusion in an acute patient population. Objectives/Methods: To establish these processes our team participated in weekly meetings and created an email group to track from time of referral to admission for therapy. All patient communication was filtered through this group. Result/Conclusion: At our center, our median time from patient referral and assessment to submission for financial clearance was 1 day (range 1-4) [Table 1]. To secure insurance clearance our financial team completed prior authorization and single case agreements for each patient. This took a median time of 12 days (range 1-36) but has shown a general decrease over time. After financial clearance our institution requires executive approval prior to submission of the purchase order before patients can undergo leukapheresis. Our executive leadership team approved and a purchase order was submitted in a median of 1 day (range 0-4). The leukapheresis procedure was scheduled and completed in a median of 5 days (range 2-12). Our team waits for confirmation that the product Table 1 Timeline from Patient Referral to Admission for CAR-T Infusion Patient Product Insurance Insurance Exec Leadership Purchase Leukapheresis Admit Time from referral LOS (d) auth (d) Approval (d) Approval (d) Order (d) (d) to admission (d)
Table 1 Chemical stability of CE Melphalan 2mg/ml and 5 mg/ml solutions CE Melphalan solution and storage temperature
Percent of initial concentration remaining at these time intervals
2h 4h 6h 8h 12 h CE Melphalan 2 mg/ml solution in 0.9% sodium chloride IV (PVC) bags 4°C 97.91 § 2.92 102.11 § 3.82 99.05 § 5.75 98.79 § 3.95 96.37 § 2.12 23°C 101.1 § 2.77 97.56 § 2.0 100.72 § 2.76 97.92 § 1.07 95.81 § 1.97 CE Melphalan 5mg/ml reconstituted solution in glass vial 4°C 23°C
24 h 95.87 § 1.01 93.77 § 1.80 99.84 § 1.38 99.44 § 2.36
1 2 3 4 5 6 7 8 9 10 11 12 13 Median
A A A A T A A (INV) A (INV) T A (INV) A (INV) A A
1 0 1 4 1 0 1 1 1 1 1 3 1 1
LOS=length of stay A=axicabtagene ciloleucel T=tisagenlecleucel
16 14 12 36 16 20 6 3 6 1 2 8 24 12
0 1 0 4 1 2 n/a n/a 1 n/a n/a 0 0 1
0 2 1 1 1 3 n/a n/a 1 n/a n/a 0 0 1
6 6 5 12 5 4 2 7 2 9 9 2 4 5
21 57 20 20 53 28 24 22 23 21 21 22 21 22
44 80 39 77 77 57 33 33 34 32 31 35 50 37
18 59 14 17 9 7 10 10 9 9 13 14 10 11.5
Abstracts / Biol Blood Marrow Transplant 25 (2019) S100 S289
This is a quality improvement project to help decrease the admission rate for febrile neutropenia in the hematological malignancy population. The focus will be on utilizing a checklist to help facilitate a rapid admission/discharge process. The checklist is comprised of high risk features that providers should assess all patients for. If patients have 2 or more of the risk factors they should remain inpatient per current standard of care otherwise patients should be discharged within 48 hours. Hematological malignancy patients admitted from October 2017- January 31st 2019 will be reviewed and compared to historical data on readmission rates at our institution. Preliminary data has shown a decrease in the length of admission (3 vs. 5 days) between patients where the protocol was utilized versus historical data. Reasons patients have not discharged within 48 hours has included clinician judgment, positive cultures and severe neutropenia. Data collection is ongoing and updated results will be presented at the meeting in February 2019.
418 Relapse Rates in Patients Receiving Azithromycin for the Treatment of Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplant Jade L. Kutzke PharmD1, Jodi L Taraba PharmD2, Julianna A Merten PharmD3, Mithun V. Shah MD, PhD4, Shahrukh K. Hashmi MD, MPH4, Mrinal M. Patnaik MBBS4, Mark R. Litzow MD4, William J. Hogan MD4, Hassan B. Alkhateeb MD4. 1 Pharmacy, Mayo Clinic Hospital, Rochester, MN; 2 Mayo Clinic Hospital, Rochester, MN; 3 Department of Pharmacy Services, Mayo Clinic, Rochester, MN; 4 Division of Hematology, Mayo Clinic, Rochester, MN Introduction: The FDA issued a warning on the increased risk of hematologic relapse based on the ALLOZITHRO trial, recommending azithromycin not be used long-term in patients that have undergone allogenic hematopoietic stem cell transplant (HSCT). In the ALLOZITHRO trial, azithromycin was started at the time of the conditioning regimen for prophylaxis of bronchiolitis obliterans (BO); however, at our site and many others across the country, azithromycin is initiated after BO. Objective: The goal of this study was to evaluate if azithromycin used in treatment of BO is associated with an increase in the rate of relapse. Methods: IRB approval was obtained prior to review of the electronic medical record and the Mayo Clinic HSCT database. Adult patients who received an allogeneic HSCT from January 2008 August 2018 for a malignant disease and received 2 weeks of azithromycin were included in this study. Patients were excluded if they received <2 weeks of azithromycin therapy, received azithromycin prior to 100 days post-HCST, relapsed prior to the initiation of azithromycin, or never achieved disease remission prior to starting azithromycin. Data collected via retrospective review included patient demographics, azithromycin regimen and duration, death, relapse, and date of last follow-up. Results: Of 466 adult patients who received an allogenic HSCT at Mayo Clinic Hospital-Rochester for malignant disease, 185 patients received azithromycin. Of 185 patients who received azithromycin, 87 were excluded: declined research participation (n = 7), received <2 weeks of azithromycin therapy (n = 65), azithromycin initiated prior to 100 days post-HCST (n = 11), relapse prior to the initiation of azithromycin (n = 2), or never achieved disease remission (n = 2). We identified 98 patients who met our inclusion/exclusion criteria. The median age was 56 years (23-74). The majority of patients received azithromycin 250 or 500 mg three times weekly: 500 mg three times weekly (n = 51), 250 three times weekly (n = 40). The
median time to azithromycin initiation was 16.6 months (IQR 9.4-26). The median duration of azithromycin therapy was 33.9 months (IQR 1.4-116.4). Death occurred in 2 patients (2%) and was not related to relapse. Two patients (2%) relapsed a median of 28 months (IQR 7.2-49) after transplant. The median time to relapse after azithromycin initiation was 10.4 months (IQR 2.5-18.2). The two patients who relapsed were at high risk for relapse as one had FLT3 ITD mutation in CR1 without FLT3 inhibitor treatment, and the other had heavily pretreated multiple myeloma. Both achieved remission and are alive at the time of last follow up. The median overall survival for this cohort from the start of azithromycin was not reached. Conclusion: The use of azithromycin as treatment for BO was not associated with a high incidence of disease relapse in this study. Further research is needed to confirm our findings.
419 Single-Center Experience of a Triple Drug Prophylaxis Regimen for Sinusoidal Obstructive Syndrome (SOS) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Samrah Ahmad PharmD1, Ruthee-Lu Bayer MD2, Mukesh Tiwari MBBS3. 1 Pharmacy, North Shore University Hospital, Manhasset, NY; 2 Hematology/Oncology, North Shore University Hospital, Northwell Health, Lake Success, NY; 3 Oncology, Northwell Health, Lake Success, NY Purpose: Hepatic veno-occlusive disease (VOD) or SOS is a serious and potentially fatal complication of HSCT. Due to the limited amount of data regarding prophylactic agents for VOD, the goal of this study is to determine the efficacy of the triple prophylactic regimen utilized at North Shore University Hospital (NSUH), in preventing VOD until engraftment in patients undergoing allogeneic HSCT. Methods: This retrospective cohort study included patients 18 years and older admitted to NSUH for an allogeneic HSCT during 2015-18. Patients that had known hypersensitivity to any of the prophylactic agents and/ or who were hemodynamically unstable within 24 hours of starting VOD prophylaxis were excluded. All patients received the standard regimen of continuous infusion heparin at a dose of 100 units/kg/day, Ursodiol 300 mg by mouth twice a day, and glutamine 15 gram in two divided doses. Patients were monitored closely for any weight changes and aggressive management with diuretics was utilized to avoid fluid overload and hepatic congestion. The primary outcome measure was to achieve VOD-free survival at engraftment and secondary outcomes was any adverse effects due to the regimen. Results: The study included 109 patients, 61 male, 48 female, average age of 54 years (range 20-75 years) and average weight of 81.2 kg (range 42.8-155.5kg). The patients were in the hospital for an average of 31 days (range 20-93; median 28 days). None of the patients experienced fulminant SOS/VOD as per European Society for Blood and Marrow Transplantation (EBMT) criteria. Ultrasounds were done in 3 patients, with no abnormalities suggestive of VOD. Prior to engraftment 1 patient had ascites, 2 painful hepatomegaly, 1 right upper quadrant pain, and 23 (21.1%) concurrent organ dysfunction requiring supportive care such as oxygen supplementation (5.5%) and/or Intravenous fluids (6.4%). Patient’s weight, bilirubin, AST, ALT, and serum creatinine were monitored at baseline and daily for any abnormalities. Patients experienced an average weight increase of 4% (0-7%), 11 patients (10%) had a bilirubin of greater then 2mg/dl but had no other criteria for SOS. Majority of the patients returned to their baseline (95%). Only 3 patients required discontinuation of heparin, no other
Abstracts / Biol Blood Marrow Transplant 25 (2019) S100 S289
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adverse effects were reported. All patients received diuretics for an average of 7 days (range 1-42 days) and mean dose was 46mg/day (range 20- 160mg). Of note one patient died before engraftment with possible late onset VOD, patient had elevated bilirubin and weight gain of 18.6% with trace ascites. Patient had received Inotuzumab Ozogamicin as salvage treatment prior to HSCT. Conclusion: No instances of classical SOS/VOD were reported in the 109 patients undergoing allogeneic HSCT receiving the triple therapy regimen. One patient had possible late onset VOD. The data suggests an efficacious role of the triple prophylactic drug combination in this setting.
Results: The percent concentration at various time points compared to time zero, is presented in Table 1. The percent concentration after 24 hr. of 2 mg/ml CE melphalan in an IV bag was 93.77% at RT, and 95.87% under refrigeration. The percent concentration of 5 mg/ml CE melphalan solution in a glass vials at 24 hr. was 99.44% at RT and 99.84 % under refrigeration. Conclusion: The results indicate that both 2 mg/ml CE melphalan in IV bags, and 5 mg/ml in glass vials are both stable at RT and under refrigeration for 24 hr. after preparation.
420
Timeline from Referral to Admission for CAR-T Infusion: A Single Institution Experience in an Academic Medical Center Zahra Mahmoudjafari PharmD, BCOP1, Caroline Strohm BSN, RN, OCN2, Clint L. Divine MBA, MSM3, Crissy Morrison BSN, RN4, Erin Winters RN, BSN, BMTCN, BMT5, Joseph McGuirk DO6. 1 Department of Pharmacy, University of Kansas Health System, Westwood, KS; 2 The University of Kansas Cancer Center, Westwood, KS; 3 Blood & Marrow Transplantation, Division of Hematological Malignancies & Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS; 4 University of Kansas Cancer Center, Kansas City, KS; 5 University of Kansas Hospital, Westwood, KS; 6 Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS
Stability of Captisol-Enabled Melphalan (Evomela) in 0.9% Sodium Chloride Solution in IV Bags and Glass Vials at Room Temperature and Refrigeration Jitesh D. Kawedia PharmD, PhD1, Sumankalai Ramachandran PhD2, Alison M. Gulbis PharmD1, Mark Titus PhD2, Qaiser Bashir MD3, Muzaffar H. Qazilbash MD3, Richard E. Champlin MD3, Stefan O. Ciurea MD3. 1 Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX; 2 Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; 3 Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Melphalan is an alkylating agent, which is used in intensive treatment of hematological malignancies and solid tumors. The older melphalan formulation (Alkeran) has very limited (<60 minutes) stability, which can significantly affect pharmacy operations and planned patient care. CaptisolEnabled (CE) melphalan (Evomela) is a new formulation with increased stability (4 hr. at room temperature (RT)). In this study, we have determined the stability of 2 mg/ml CE melphalan solution in IV bags and 5 mg/ml reconstituted solution in glass vials at RT and under refrigeration (4°C). Extended stability will allow time for pharmacy to prepare and distribute the IV bags for patients receiving melphalan on standard of care, ongoing studies, and for potential new studies, which would aim to investigate the benefits of prolonged infusion of melphalan. Methods: Lyophilized CE melphalan was reconstituted to 5mg/ ml with 0.9% sodium chloride (in glass vials), diluted to 2 mg/ml with 0.9% sodium chloride, in IV (PVC) bags. They were then stored at RT (23°C) and under refrigeration. Aliquots (1ml) were removed at 0, 2, 4, 6, 8, 12 and 24hr. after preparation of 2mg/ml IV bags and the concentration was analyzed by using a validated high performance liquid chromatography method. Since 5 mg/ml reconstituted vials were previously found to be stable for 24 hr., we determined its stability after 24 hr. at RT and under refrigeration. The 2 mg/ml or 5 mg/ml CE melphalan was considered stable if the concentration at a given time-point was greater than 90% of the initial concentration at time zero.
421
Introduction: Administration of chimeric antigen receptor therapy (CAR-T) requires the coordination of a multi-disciplinary team including physicians, nurses, pharmacists, apheresis and financial leaders. With the commercial approval of tisagenlecleucel and axicabtagene ciloleucel, centers were challenged with securing financial authorization, completing leukapheresis and lymphodepleting chemotherapy in a timely manner prior to cellular infusion in an acute patient population. Objectives/Methods: To establish these processes our team participated in weekly meetings and created an email group to track from time of referral to admission for therapy. All patient communication was filtered through this group. Result/Conclusion: At our center, our median time from patient referral and assessment to submission for financial clearance was 1 day (range 1-4) [Table 1]. To secure insurance clearance our financial team completed prior authorization and single case agreements for each patient. This took a median time of 12 days (range 1-36) but has shown a general decrease over time. After financial clearance our institution requires executive approval prior to submission of the purchase order before patients can undergo leukapheresis. Our executive leadership team approved and a purchase order was submitted in a median of 1 day (range 0-4). The leukapheresis procedure was scheduled and completed in a median of 5 days (range 2-12). Our team waits for confirmation that the product Table 1 Timeline from Patient Referral to Admission for CAR-T Infusion Patient Product Insurance Insurance Exec Leadership Purchase Leukapheresis Admit Time from referral LOS (d) auth (d) Approval (d) Approval (d) Order (d) (d) to admission (d)
Table 1 Chemical stability of CE Melphalan 2mg/ml and 5 mg/ml solutions CE Melphalan solution and storage temperature
Percent of initial concentration remaining at these time intervals
2h 4h 6h 8h 12 h CE Melphalan 2 mg/ml solution in 0.9% sodium chloride IV (PVC) bags 4°C 97.91 § 2.92 102.11 § 3.82 99.05 § 5.75 98.79 § 3.95 96.37 § 2.12 23°C 101.1 § 2.77 97.56 § 2.0 100.72 § 2.76 97.92 § 1.07 95.81 § 1.97 CE Melphalan 5mg/ml reconstituted solution in glass vial 4°C 23°C
24 h 95.87 § 1.01 93.77 § 1.80 99.84 § 1.38 99.44 § 2.36
1 2 3 4 5 6 7 8 9 10 11 12 13 Median
A A A A T A A (INV) A (INV) T A (INV) A (INV) A A
1 0 1 4 1 0 1 1 1 1 1 3 1 1
LOS=length of stay A=axicabtagene ciloleucel T=tisagenlecleucel
16 14 12 36 16 20 6 3 6 1 2 8 24 12
0 1 0 4 1 2 n/a n/a 1 n/a n/a 0 0 1
0 2 1 1 1 3 n/a n/a 1 n/a n/a 0 0 1
6 6 5 12 5 4 2 7 2 9 9 2 4 5
21 57 20 20 53 28 24 22 23 21 21 22 21 22
44 80 39 77 77 57 33 33 34 32 31 35 50 37
18 59 14 17 9 7 10 10 9 9 13 14 10 11.5