Pharmacoeconomic Impact of Upfront Use Plerixafor for Autologous Stem Cell Mobilization in Multiple Myeloma Patients

Abstract Abstract 2075 The most commonly employed agent for upfront stem cell mobilization is granulocyte-colony-stimulating factor (G-CSF), which is associated with about 25% of unsuccessful mobilization. Plerixafor was granted FDA approval based on improved rate of successful mobilization as an upfront mobilizing agent. However, because of its cost, it is often reserved for patients who failed previous standard mobilization. This strategy can increase the number of apheresis and potentially delay treatment. This retrospective study, performed between January 2008 and April 2011, included 50 adult patients with multiple myeloma (MM) who underwent ASCT. Twenty-five patients received plerixafor, in combination with G-CSF, and 25 patients received G-CSF alone as an upfront mobilization therapy. Plerixafor was given as 0.24mg/kg/day SC in the evening for up to 4 days, starting on day 4 of G-CSF. For stem cell collection, G-CSF was given as 10mcg/kg/day SC in the morning for 5 days. Targets of collection were minimal 5 x106 and optimal 107 CD34+ cells/kg. After ASCT, G-CSF was given as 5mcg/kg/day IV from day 0 until engrafted. In April 2010, a practice change was instituted to delay initiation of G-CSF from day 0 to day +5 following ASCT. Simultaneously, plerixafor was used, in combination with G-CSF, as an upfront mobilization therapy for autologous stem cell mobilization in MM patients. The primary objective of this study was to assess pharmacoeconomic impact of using plerixafor as an upfront mobilization therapy in patients with MM. There were no differences in age (mean, 57.4±8.7 yrs vs. 56.4±6.3 yrs; p=NS), weight (mean, 74.6±15.9kg vs. 75±19.7kg; p=NS), number of previous SCT (mean, 0±0.2 vs. 0.1±0.3; p=NS), patients with relapsed disease (16% vs. 16%; p=NS) or melphalan dose (mean, 192.8±19.9mg vs. 192.8 ±19.9mg; p=NS) between plerixafor group and the control. Compared with the control, plerixafor mobilizations yielded higher CD34+ cell content [mean (x106 CD34+ cells/kg), 16.1±9.7 vs. 8.4±4.6; p=0.0007], higher number of CD 34+cells infused [mean (x106 CD34+ cells/kg), 7.6±4.6 vs. 4.4±1.7; p=0.0017], required fewer number of G-CSF doses for both stem cell collection (mean, 5.9±1.1 vs. 7.1±1; p=0.0001) and for neutrophil recovery (mean, 8±1.8 vs. 11.8±1.1; p<0.0001), and required fewer number of apheresis (mean, 1.9±1.1 vs. 3.1±1; p=0.0001). The plerixafor group had a longer time to neutrophil engraftment compared with the control (mean, 10.8±0.9 days vs. 9.8±0.9 days; p<0.0001); however, this did not translated to longer days of hospitalization post-ASCT (mean, 15.2±2.7 days vs. 14.1±3.1 days; p=NS). The plerixafor group required fewer G-CSF doses for both mobilization and neutrophil recovery, and fewer apheresis sessions. Therefore, this group had a lower cost of G-CSF per patient for both stem cell collection (mean, $2,212±572 vs. $2,765±487, p=0.0006) and for stem cell recovery (mean, $1,677±521 vs. $2,653±1,125, p=0.0003), and also lower cost of apheresis per patient (mean, $889±517 vs. $1,476±479; p=0.0001). The mean number of plerixafor doses per patient was 1.8±1, with a cost per patient of $9,081.6±5,220. Based on our interim data for overall cost analysis, the plerixafor group had similar cost for blood products per patient (mean, $2,803±3,049 vs. $2,332±1,160, p=0.49), overall cost of medications (mean, $19,461±5,307 vs. $22,442±5,451, p=0.13), overall cost of hospitalization (mean, $60,646±13,981 vs. $61,474±10,464, p=0.84), and cost of hospitalization and apheresis combined per patient (mean, $61,632±14,163 vs. $62,949±10,298, p=0.75). This data suggests that using plerixafor for upfront autologous stem cell mobilization in patients with MM significantly improves success rate of mobilization, decreases the number of apheresis sessions, and does not have a substantial pharmacoeconomic impact. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Stem Cell Mobilization after Various Induction Regimens in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.5433.5433 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5433-5433

Author(s):

Jakub Radocha ◽

Vladimir Maisnar ◽

Miriam Lanska ◽

Jiri Hanousek ◽

Katerina Machalkova ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Conflicts Of Interest ◽

Rapid Development ◽

Autologous Transplantation ◽

Stem Cell Mobilization ◽

High Dose ◽

Cell Transplant ◽

Cell Mobilization ◽

Stem Cell Collection

Abstract Stem cell mobilization after various induction regimens in patients with multiple myeloma Introduction: Rapid development of novel therapies for multiple myeloma has led to a significant improvement in response to the treatment. Stem cell mobilization before autologous stem cell transplantation is a source of considerable costs of transplant procedure. Whether modern induction regimens affect outcome of stem cell mobilization has not been extensively studied. Aim: The goal of this study was to compare efficacy of stem cell mobilization after different induction regimens in patients with multiple myeloma. The primary goal was to compare CTD (cyclophosphamide, thalidomide, dexamethasone), CVD (cyclophosphamide, bortezomib, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) and regimens in terms of succesful stem cell collection. Methods: All patients with multiple myeloma who have been planned for stem cell collection and were treated with one of the above mentioned regimens were included in this retrospective analysis. The demographic data, amount of stem cells collected, number of days needed to reach the target collection were recorded. All patients received high dose cyclophosphamide 2,5 g/m2 prior to stem cell collection and were primed with G-CSF twice daily from day 5. The collection was started at day 10. Collection goal was 8x106/kg CD34+ cells. Results: 15 patients received CTD, 25 patients CVD and 16 patients VTD regimen before stem cell collection. Groups were comparable according to age, gender and myeloma stages. Mean collected cells at the end of collection were 9.2 (SD 2.8) for CTD, 12.3 (SD 5.6) for CVD and 10.1 (SD 2.1) for VTD (p=0.066). Mean daily harvest was 3.4, 8.0 and 7.6 x106/kg respectively (p=0.01). Mean days needed to reach desired harvest were 3, 2.25 and 1.6 days (p=0.001). No collection failure was observed. Conclusion: The best collection results were seen in patients after induction with CVD or VTD regimen. VTD regimen also required the least days for collection and seems to be most beneficial for cost of collection. CTD regimen shows the least efficacy in stem cell collection before autologous transplantation. All patients managed to harvest for at least one stem cell transplant. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Cyclophosphamide Overcomes the Suppressive Effect of LenalidomideTherapy on Stem Cell Collection in Preparation for Autologous Stem Cell Transplantation for Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.3024.3024 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3024-3024

Author(s):

Tomer Mark ◽

David Jayabalan ◽

Roger N. Pearse ◽

Jessica Stern ◽

Jessica Furst ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Induction Therapy ◽

Stem Cell Mobilization ◽

Cd34 Cells ◽

Cell Mobilization ◽

Stem Cell Collection

Abstract Multiple Myeloma (MM) therapy has evolved over recent years to include powerful new therapeutic agents. The goal for most patients with MM, however, still remains high-dose chemotherapy followed by autologous stem cell transplantations as this procedure has been proven to have a therapeutic benefit. Therefore, the selection of an induction therapy must take into consideration the potential impact on the ability to collect enough stem cells for future transplantation. Recent studies have discussed difficulty in collecting stem cells in patients receiving lenalidomide-based induction therapy using filgastrim (G-CSF) in preparation for autologous stem cell transplantation in MM. It also has been recommended that the duration of lenalidomide induction therapy be limited to 4–6 cycles, since longer treatment time can hinder collection yields. We sought to determine if the addition of cyclophosphamide (CTX) to G-CSF as a mobilization regimen could rescue the ability to collect adequate stem cells for at least two autologous stem cell transplants for patients who had induction therapy with the BiRD (Biaxin® [clarithromycin]/Revlimid® [lenalidomide]/dexamethasone) regimen. BiRD therapy is as follows for each 28-day cycle: Clarithromycin 500mg po BID for days 1–28, Lenalidomide 25mg po daily for days 1–21, and Dexamethasone 40mg po weekly on days 1, 8, 15, and 21. All patients had either Stage II or III MM by Salmon-Durie criteria and were treatment naïve. Patients were advised to undergo stem cell collection after either maximum disease response or disease plateau had been achieved. Prior to stem cell mobilization, BiRD therapy was held for a minimum of 14 days. Stem cell collection was performed after either G-CSF alone at a dose 10 mcg/kg/day for 5–10 consecutive days until a total of 10 × 106/kg CD34+ stem cells had been collected or with the addition of cyclophosphamide (CTX) at a dose of 3g/m2 once prior to the initiation of G-CSF therapy. A total of 28 patients underwent stem cell collection. Stem cell mobilization was attempted with G-CSF alone in 9 instances and with CTX+G-CSF in 20 instances (1 patient underwent mobilization with both G-CSF alone and CTX+G-CSF). In comparison to the G-CSF monotherapy, CTX+G-CSF yielded a significantly greater stem cell collection (mean CD34+ cells collected: 3.78 × 106/kg vs. 32.33 × 106/kg, P < 0.0001). Only 33% of patients who attempted stem cell mobilization with G-CSF alone obtained sufficient CD34+ cell yield vs. 100% of the patients mobilized with CTX+G-CSF (P < 0.0001). The extent of BiRD therapy prior to stem cell mobilization ranged from 2–27 cycles. The number of cycles of BiRD did not significantly impact the success rate of stem cell collection (P = 0.14). In conclusion, the patients mobilized with CTX+G-CSF had a higher number of CD34+ cells collected and were all able collect enough stem cells for two autologous transplants. There was no association with the duration of BiRD therapy and successful CD34+ cell collection. We therefore recommend continuing lenalidomide-based induction therapy until desired tumor reduction goal is achieved and using the CTX in addition to G-CSF to ensure successful stem cell harvest prior to autologous transplantation.

Download Full-text

Fractionated High-Dose Cyclophosphamide and G-CSF: An Extremely Effective Chemo-Mobilization Modality In Patients With Multiple Myeloma

Blood ◽

10.1182/blood.v122.21.4521.4521 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4521-4521

Author(s):

Ahmad Antar ◽

Zaher K. Otrock ◽

Nadim El Majzoub ◽

Nabila Kreidieh ◽

Muhammad Muhammad ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Febrile Neutropenia ◽

Median Time ◽

Stem Cell Mobilization ◽

Fixed Dose ◽

High Dose ◽

Cd34 Cells ◽

Cell Mobilization ◽

Stem Cell Collection

Background The optimal stem cell mobilization regimen for multiple myeloma (MM) is undefined. Most centers use either granulocyte-colony stimulating factor (G-CSF) alone (steady state strategy) or cyclophosphamide (CY) followed by G-CSF (chemo-mobilizing strategy). However, the impact of CY dose on stem cell yield and subsequent engraftment, and toxicity is unknown. We retrospectively analyzed our experience using fractionated high-dose CY and G-CSF as our preferred chemo-mobilization strategy in MM patients (pts) and its impact on the mobilization outcomes, engraftment and the observed toxicity. Methods Between 01/2000 and 12/2012, 220 chemo-mobilization attempts were undertaken. Among these, 62 pts (M=37, F=25) had MM (1st-line=54, relapsed=8) and all received high-dose CY and G-CSF. Median age was 56 (37-75) yrs. ISS stage was I (n=34), II (n=16), and III (n=12). Pre-transplant induction consisted of VAD or VAD-like chemotherapy (n=26), bortezomib(bor)/dexamethasone (dex) (n=15), thalidomide (thal) /dex (n=10), bor/thal/dex (n=10), and 1 received bor/lenalidomide/dex. Fifty-six received fractionated high-dose CY (5g/m2 divided in 5 doses of 1g/m2 q 3 hrs) whereas 6 received CY 50 mg/kg for 2 doses. G-CSF was given at a fixed dose of 300 µg SQ q 12 hrs. Results All 62 (100%) pts achieved a circulating CD34 count ≥20/µl which is the cut-off level at our center to proceed with apheresis. The median peak peripheral blood CD34+ cell count was 111.5 (21-575) cells/μL. Success rate of stem-cell mobilization defined as collection of more than 2x106 CD34+ cells/kg was 100%. Median stem cell collection yield was 15.9x106 CD34+ cells/kg. Moreover, 61 (98.4%) pts and 46 (74%) pts collected >5x106 and >10x106 CD34+ cells/kg, respectively. Only 4 (6.4%) pts required 2 apheresis sessions. Conversely, 40 (64.5%) pts required hospitalization for febrile neutropenia (n=38) or transfusion support (n=2) for a median of 4 (1-8) days. No one required intensive level of care and all recovered. Also, 17 (27.4%) pts required blood transfusions and 16 (25.8%) required platelets transfusion. Autografting was successfully performed in all pts using high-dose melphalan with a median time from mobilization to the first transplant of 31 (16-156) days and median infused CD34+ cells of 7x106/kg (3.1-15.3). All pts achieved successful hematologic engraftment with a median time for neutrophil engraftment (ANC ≥500/µL) of 11 days and platelet engraftment (platelet ≥20000/microliter) of 12 days. Conclusion Fractionated high-dose CY and G-CSF is a highly effective chemo-mobilization strategy in MM in terms of successful rate of mobilization (100%), efficiency of stem cell collection (high yield), and timely hematologic engraftment (100%). However, the relatively high-rate of hospitalizations for febrile neutropenia requires an assessment of its cost-efficiency as compared to new mobilization strategies using G-CSF and preemptive plerixafor. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Clinical Impact and Resource Utilization After Stem Cell Mobilization Failure in Patients with Multiple Myeloma and Lymphoma.

Blood ◽

10.1182/blood.v114.22.2142.2142 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2142-2142

Author(s):

Morie A Gertz ◽

Robert Wolf ◽

Ivana N. Micallef ◽

Dennis A. Gastineau

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Growth Factors ◽

Hodgkin Lymphoma ◽

Resource Utilization ◽

Stem Cell Mobilization ◽

Hodgkin Disease ◽

Non Hodgkin Lymphoma ◽

Cd34 Cells ◽

Cell Mobilization

Abstract Abstract 2142 Poster Board II-119 High-dose chemotherapy in conjunction with autologous SCT is the preferred treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma and newly diagnosed multiple myeloma. Failure to achieve optimal stem cell mobilization results in multiple subsequent attempts, which consumes large amounts of growth factors and potentially requires antibiotics and transfusions. We retrospectively reviewed the natural history of stem cell mobilization attempts at our institution from 2001 through 2007 to determine the frequency of suboptimal mobilization in patients with hematologic malignancy undergoing autologous transplant and analyzed the subsequent resource utilization in patients with initially failed attempts. Of 1,775 patients undergoing mobilization during the study period, stem cell collection (defined by the number of CD34+ cells/kg) was “ optimal” (≥5×106) in 53%, “low” (≥2 to 5×106) in 25%,“ poor” (<2×106) in 10%, and “failed” (<10 CD34+ cells/mL) in 12%. In the 47% of collections that were less than optimal, increased resource consumption included increased use of growth factors and antibiotics, subsequent chemotherapy mobilization, increased transfusional support, more apheresis procedures, and more frequent hospitalization. Other costs often omitted include the need for hospitalization, which was seen in 5% to 11% of the patients in our study. Parenteral antibiotics were needed when fever developed in 7% of patients with Hodgkin disease, 4% with non-Hodgkin lymphoma, and 24% with multiple myeloma who underwent mobilization using a chemotherapy pulse. When stem cell mobilization was not immediately optimal, subsequent attempts to mobilize failed completely in 3 of 42 patients (7%) with Hodgkin disease (3% of the original Hodgkin disease cohort), 56 of 157 (36%) with multiple myeloma (6% of the original myeloma cohort), and 50 of 328 (15%) with non-Hodgkin lymphoma (7% of the original non-Hodgkin lymphoma cohort). These usually unappreciated costs of stem cell mobilization failure highlight the need for more effective mobilization strategies. Disclosures: Gertz: genzyme: Research Funding.

Download Full-text

High Number of Successful Mobilizations Associated with the Use of Plerixafor and Colony Stimulating Factors In Patients with Multiple Myeloma (MM) and Lymphoma Treated at Memorial Sloan-Kettering Cancer Center

Blood ◽

10.1182/blood.v116.21.2263.2263 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2263-2263

Author(s):

Nelly G. Adel ◽

Mathew Sherry ◽

Stephen J. Harnicar ◽

Emily Mccullagh ◽

Heather Landau ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Adult Patients ◽

Stem Cell Mobilization ◽

Cancer Center ◽

Published Data ◽

First Line ◽

Colony Stimulating Factors ◽

Cd34 Cells ◽

Cell Mobilization

Abstract Abstract 2263 Background: Autologous stem cell transplantation (ASCT) remains the only curative option for many lymphoma patients and it is an integral component of treatment for patients with multiple myeloma (MM). Stem cell mobilization has most commonly been performed using either chemotherapy and colony-stimulating factors or colony stimulating factors alone. This approach was challenged by the inability to collect enough CD 34 cell count to perform an ASCT. Plerixafor (Mozobil ®) previously known as AMD3100, a selective antagonist of CXCR4, has recently been approved for ASCT mobilization in combination with granulocyte- colony stimulating factor (G-CSF) for both multiple myeloma and lymphoma patients and is effective for patients who failed to mobilize enough CD34 cells with other modalities. Patients and Methods: This retrospective study examines all adult patients with MM and lymphoma who received plerixafor as a mobilization agent for ASCT at Memorial Sloan- Kettering Cancer Center between January 1st, 2009 and August 1st, 2010. Patient's information was obtained from the pharmacy data base and electronic medical records. Data included demographics, diagnosis, first line mobilization regimen, second and third line regimens, doses of plerixafor received, number of pheresis sessions and CD34 cells per kg collected per each session. The primary objective was to determine how many patients failed stem cell collection following mobilization at our center. Results: Fifty-six adult patients with lymphoma (N=23) and MM (N=33) were identified. Patients were excluded if they were treated for a pediatric malignancy or an alternate diagnosis. The average number of pheresis and CD34 cells/kg collected in each group are shown Table 1. Forty-three percent (10/23) patients with lymphoma received plerixafor and G-CSF as the first line option for mobilization and 57% (13/23) received plerixafor and G-CSF after failing other regimens. A total of 5 (22%) patients with lymphoma failed collection following mobilization with plerixafor, 1 as a primary mobilization failure and 4 having failed other mobilization strategies. Thirty-nine percent (13/33) of patients with MM received plerixafor and G-CSF as the first line option for mobilization and 61% (20/33)after failing other regimens, including cyclophosphamide (N=15) and G-CSF alone (N=5). Among the patients mobilized with plerixafor, 6% (2/33) failed collection, 1 who received plerixafor and G-CSF for primary mobilization and only 1 after failing other regimens. Conclusion: In lymphoma and MM patients plerixafor in combination with G-CSF is effective for stem cell mobilization and in this study we report higher success rates than in previously published data. The few number of failures with plerixafor plus G-CSF given as a primary mobilization regimen, supports its use in this setting and is attractive considering that it can reduce patient's exposure to chemotherapy. Disclosures: Matasar: Genzyme Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

A Pilot Study of Peripheral Blood Hematopoietic Stem Cells Mobilization with the Combination of Bortezomib and G-CSF in Multiple Myeloma and Non-Hodgkin's Lymphoma Patients.

Blood ◽

10.1182/blood.v126.23.1902.1902 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1902-1902

Author(s):

Divaya Bhutani ◽

Vidya sri Kondadasula ◽

Joseph P. Uberti ◽

Voravit Ratanatharathorn ◽

Lawrence G. Lum ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Peripheral Blood ◽

Median Number ◽

Peripheral Blood Cd34 ◽

Cd34 Cells ◽

Group A ◽

Cell Mobilization ◽

Group B ◽

Stem Cell Collection

Abstract Background: Bortezomib has become an integral part of front-line therapy of multiple myeloma in a large majority of patients. There are preliminary reports which show that addition of bortezomib can augment the peripheral blood CD34 count during stem cell mobilization. In this single center prospective trial we added bortezomib to G-CSF to evaluate the effects of bortezomib on peripheral CD34 counts and collection. Methods: Patients aged 18-70 years with diagnosis of multiple myeloma (MM) or non-hodgkin's lymphoma (NHL) who were eligible for autologous stem cell transplantation (ASCT) and had received no more than three prior chemotherapeutic regimens were eligible for the study. Patients were enrolled in two groups. Group A (N=3) received G-CSF 16mcg/kg for 5 days and proceeded to stem cell collection on D5 and then received bortezomib 1.3mg/m2 on D5 after stem cell collection and G-CSF 16mcg/kg on D6, 7, 8 and repeat stem cell collection on D6, 7, 8 till the goal was achieved. Group B (N=17) received G-CSF 16mg/kg on D1-5 and received bortezomib 1.3mg/m2 on D4 and proceeded to stem cell collection on D5. If the patient was not able to collect the predefined goal CD34, G-CSF was continued on D 6, 7, 8 and a second dose of bortezomib 1.3mg/m2 was given on D7. Mobilization procedure was stopped once the predefined goal CD34 collection (4 x 106/kg for MM and 2 x 106/kg for NHL) had been collected. Primary objectives of the study was to determine if addition of bortezomib to G-CSF will result in an increase in PBSCs by > 2-fold and to achieve median neutrophil engraftment 12 days post ASCT. Secondary objectiveswere to evaluate the collected product for co-mobilization of lymphoma or myeloma cells and to determine if the use of bortezomib increases the mobilization of immune-stimulatory Dendritic cell (DC) -1 subsets. Results: A total of 23 patients were enrolled and 20 were evaluable for the results. Only one patient with NHL was enrolled and rest had MM. Median age of pts was 57 years, M/F 8/12, median number of previous chemotherapy regimens was 1 (range 1-3). The median peripheral blood CD34 count pre and post bortezomib in all patients were 28.8 x 106/kg and 37 x 106/kg respectively. All three patients in group A had drop in peripheral blood CD34 counts on D6 post bortezomib as they had undergone stem cell collection on day 5. In part B (N=17), 15 patients had increase in peripheral blood CD 34+ve cell counts with 4 patients achieved doubling while 11 pts had less than doubling of peripheral blood CD34 count after receiving bortezomib. Two patients had minimal drop in the peripheral blood CD34 counts post bortezomib. Median number of CD34 cells collected in15 patients (part B) were 5.06 x 106 CD34 cells/kg (range 4-15.1). 18 patients proceeded to ASCT and median time to neutrophil engraftment (ANC ≥500/cumm) post transplant was 12 days (range 11-16) and platelet engraftment (Plt count ≥ 20,000/cumm) was 18 days (range 15-27). There was no significant change in DC1/DC2 ratio in both groups following treatment with bortezomib and G-CSF (Figure 1). In group A all three patients collected goal CD34 count on day 5 and 2/3 patients collected >4 x106 CD34 cells/kg on D6 post bortezomib and1/3 patients collected 2.6 x 106 on D6 post bortezomib. In group B (n=17), 2 patients were unable to collect because of low CD34 counts on D4 and D5, 11 pts collected the goal in one day (D 5) and 4 pts required two days of apheresis (D 5 and 6). None of the patients received D7 bortezomib. Conclusion: Use of bortezomib during autologous stem cell collection was safe and well tolerated. Majority of patients had increase in peripheral blood CD34 counts post bortezomib administration on D4. Future trials should explore bortezomib as an alternate strategy to chemo-mobilization in combination with growth factors. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 2. Figure 2. Disclosures Off Label Use: Bortezomib for stem cell mobilization. Lum:Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding. Abidi:celgene: Speakers Bureau; Millenium: Research Funding.

Download Full-text

G-CSF Plus Preemptive Plerixafor Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma: Effectiveness, Safety and Cost Analysis

Blood ◽

10.1182/blood.v124.21.5823.5823 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5823-5823

Author(s):

Ahmad Antar ◽

Zaher Otrock ◽

Mohamed Kharfan-Dabaja ◽

Hussein Abou Ghaddara ◽

Nabila Kreidieh ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Peripheral Blood ◽

Stem Cell Mobilization ◽

Cell Yield ◽

Fixed Dose ◽

High Dose ◽

Peripheral Blood Cd34 ◽

Cd34 Cells ◽

Cell Mobilization

Abstract Introduction: The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. Most transplant centers use either a chemo-mobilization strategy using cyclophosphamide (CY) and granulocyte-colony stimulating factor (G-CSF) or a steady state strategy using G-CSF alone or with plerixafor in case of mobilization failure. However, very few studies compared efficacy, toxicity and cost-effectiveness of stem cell mobilization with cyclophosphamide (CY) and G-CSF versus G-CSF with preemptive plerixafor. In this study, we retrospectively compared our single center experience at the American University of Beirut in 89 MM patients using fractionated high-dose CY and G-CSF as our past preferred chemo-mobilization strategy in MM patients with our new mobilization strategy using G-CSF plus preemptive plerixafor. The change in practice was implemented when plerixafor became available, in order to avoid CY associated toxicity. Patients and methods: Patients in the CY group (n=62) (Table 1) received either fractionated high-dose CY (n=56) (5g/m2 divided in 5 doses of 1g/m2 every 3 hours) or CY at 50mg/kg/day for 2 doses (n=6). G-CSF was started on day +6 of chemotherapy at a fixed dose of 300 µg subcutaneously every 12 hours. All patients in the plerixafor group (n=27) (Table 1) received G-CSF at a fixed dose of 300 µg subcutaneously every 12 hours daily for 4 days. On day 5, if peripheral blood CD34+ was ≥ 20/µl, apheresis was started immediately. Plerixafor (240 µg/kg) was given 7-11 hours before the first apheresis if CD34+ cell count on peripheral blood on day 5 was <20/µl and before the second apheresis if CD34+ cells on the first collect were <3х106/kg. The median number of prior therapies was 1 (range: 1-3) in both groups. Results: Compared with plerixafor, CY use was associated with higher median peak peripheral blood CD34+ counts (35 vs 111 cells/µl, P= 0.000003), and total CD34+ cell yield (7.5 х 106 vs 15.9 х 106 cells/kg, P= 0.003). All patients in both groups collected ≥4x106 CD34+ cells/Kg. Moreover, 60 (96.7%) and 46 (74.2%) patients in the CY group vs 24 (88.8%) and 6 (22%) patients in the plerixafor group collected >6х106 and >10x106 CD34+ cells/kg, respectively (P=0.16; P<0.00001). Only 4 (6.4%) patients required two apheresis sessions in the CY group compared to 11 (40%) in the plerixafor group (P=0.0001). Conversely, CY use was associated with higher frequency of febrile neutropenia (60% vs 0%; P<0.00001), blood transfusions (27% vs 0%; P<0.00001), platelets transfusion (25% vs 0%; P<0.00001) and hospitalizations (64% vs 0%; P<0.00001). No one required intensive level of care and all recovered. Autografting was successfully performed in all patients using high-dose melphalan with a median time from mobilization to the first transplant of 31 days (range: 16-156) in the CY group compared to 13 days (range: 8-40) in the plerixafor group (P=0.027); and median infused CD34+ cells were 7х106/kg (range: 3.1-15.3) versus 5.27 (2.6-7.45), respectively (P=0.002). The average total cost of mobilization using the adjusted costs based on National Social Security Fund (NSSF) prices in Lebanon in the plerixafor group was slightly higher compared with the CY group ($7964 vs $7536; P=0.16). Conclusions: Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with two-fold stem cell yield, slightly lower cost (including cost of hospitalization) but significantly increased toxicity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Bortezomib Given in Sequence with Anthracycline and Thalidomide-Containing Regimens Does Not Adversely Affect Stem Cell Mobilization and Engraftment in Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v104.11.541.541 ◽

2004 ◽

Vol 104 (11) ◽

pp. 541-541

Author(s):

Geoffrey L. Uy ◽

Nicholas M. Fisher ◽

Steven M. Devine ◽

Hanna J. Khoury ◽

Douglas R. Adkins ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Peripheral Blood ◽

Stem Cell Mobilization ◽

High Dose ◽

Hematopoietic Stem ◽

Cd34 Cells ◽

Cell Mobilization ◽

High Dose Melphalan

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the 26S proteasome proven to be safe and effective in the treatment of relapsed or refractory multiple myeloma (MM). While high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT) remains the standard of care, there is considerable interest in incorporating bortezomib into the initial treatment of MM. However, the role of bortezomib in frontline therapy for MM will depend in part on its effects on subsequent stem cell mobilization and engraftment. We conducted a pilot study of bortezomib administered pretransplant followed by high-dose melphalan with AHSCT. Two cycles of bortezomib 1.3 mg/m2 were administered on days 1, 4, 8, and 11 of a 21-day treatment cycle. One week after the last dose of bortezomib, stem cell mobilization was initiated by administering filgrastim 10 mcg/kg/day subcutaneously on consecutive days until stem cell harvest was completed. Stem cell collection began on day 5 of filgrastim via large volume apheresis (20 L/day) performed daily until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Patients were subsequently admitted to the hospital for high-dose melphalan 100 mg/m2/day x 2 days followed by reinfusion of peripheral blood stem cells 48 hours later. Sargramostim 250 mcg/m2/day subcutaneously was administered starting day +1 post-transplant and continued until the absolute neutrophil count (ANC) ≥ 1,500/mm3 for 2 consecutive days. To date, 23 of a planned 40 patients have been enrolled in this study with 19 patients having completed their initial therapy with bortezomib followed by AHSCT. Patient population consists of 16 male and 7 female patients with the median age at diagnosis of 58 years (range 38–68). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (16), IgA (7) with stage II (9) or stage III (14) disease. Prior to receiving bortezomib, 11 patients were treated with VAD (vincristine, Adriamycin and dexamethasone) or DVd (Doxil, vincristine and dexamethasone), 5 patients with thalidomide and 5 patients with both. Two patients did not receive any prior chemotherapy. All patients successfully achieved the target of 2.5 x 106 CD34+ cells/kg in either one (15/19 patients) or two (4/19 patients) collections with the first apheresis product containing a mean of 5.79 x 106 CD34+ cells/kg. Analysis of peripheral blood by flow cytometry demonstrated no significant differences in lymphocyte subsets before and after treatment with bortezomib. Following AHSCT, all patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (time to platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 12 days (range 9–30 days). Eleven patients were evaluable for response at 100 days post-transplant. Compared to pre-bortezomib paraprotein levels, 3 patients achieved a CR or near CR, 7 maintained a PR while 1 patient developed PD. We conclude that pretransplant treatment with 2 cycles of bortezomib does not adversely affect stem cell yield or time to engraftment in patients with MM undergoing AHSCT. Updated results and detailed analysis will be available at the time of presentation.

Download Full-text

Cost Analysis of Using Plerixafor Plus G-CSF Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma Patients Treated At Memorial Sloan-Kettering Cancer Center (MSKCC),

Blood ◽

10.1182/blood.v118.21.4059.4059 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4059-4059 ◽

Cited By ~ 2

Author(s):

Nelly G. Adel ◽

Elaine Duck ◽

Karen Collum ◽

Emily Mccullagh ◽

Lilian Reich ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Cost Analysis ◽

Stem Cell Mobilization ◽

Outpatient Basis ◽

First Line ◽

Salvage Regimen ◽

Cell Mobilization ◽

The Cost ◽

Stem Cell Collection

Abstract Abstract 4059 Background: The combination of cyclophosphamide plus G-CSF has been the standard approach for autologous stem cell mobilization in Multiple Myeloma (MM) patients treated at MSKCC for many years. However with the recent FDA approval of plerixafor and its proven efficacy for stem cell collection in patients who had failed collection with cyclophosphamide and G-CSF, the use of plerixafor as first line agent has been advocated for patients with MM. Although proof of improved efficacy of such an approach over G-CSF/cyclophosphamide mobilization remains paramount, comparison of cost analysis between the 2 approaches is also an important parameter that needs to be considered before endorsing plerixafor as first line mobilization agent. Study Design and Method: We performed a retrospective analysis of all MM patients treated between 11/2008 and 3/2011 who received either cyclophosphamide plus G-CSF or plerixafor plus G-CSF as first line mobilization regimen. During this period of time, the target number of stem cell collection was 10 × 106stem cells/kg and patients collecting less than 4 × 106 stem cells/kg were considered mobilization failures and had a second attempt at stem cell mobilization using an alternative approach. Some patients received plerixafor as salvage regimen after failing cyclophosphamide mobilization, while others were re-challenged with a second cycle of plerixafor with cyclophosphamide and G-CSF after failing first line upfront plerixafor mobilization. Mobilization costs accounted for both groups included the costs associated with upfront mobilization, the second line mobilization in patients failing a first mobilization, as well as complications directly related to the mobilization procedures and consist of the following: Costs of drugs cyclophosphamide 3000 mg/m2, plerixafor 0.24 mg/kg, G-CSF 10 mcg/kg per dose administered prior and during pheresis sessions; hospitalization for cyclophosphamide administration; pheresis sessions; laboratory tests on pheresis days; and re-hospitalization occurring within 15 days of either mobilization approaches and considered directly related to the mobilization procedure. All costs were calculated using the institution's ratio of cost to charges, and were normalized and adjusted based on institutional charges for 2010. Results: Ninety-eight patients received cyclophosphamide and G-CSF while thirty-five patients received plerixafor as first line mobilization regimens. Eleven (11%) patients were readmitted due to cyclophosphamide complications, with an average hospital stay of 6.9 days, while none in the plerixafor arm was hospitalized. Twenty-one (21%) of the cyclophosphamide group failed mobilization and received plerixafor as salvage regimen of which 3 (3.1%) failed again and are considered ultimate failures. Two (6%) patients failed upfront mobilization with plerixafor and failed salvage mobilization and are considered ultimate failures (6%). The average number of pheresis sessions performed was 3.4 and 2.2 in the cyclophosphamide and plerixafor upfront groups respectively. In total the average cost per patient who received cyclophosphamide was 1.6 times greater than that of the patients who received plerixafor upfront. Conclusion: This cost analysis indicates that the use of plerixafor upfront for stem cell mobilization may be more cost effective than the current widely used approach employing cyclophosphamide. The cost difference between the two approaches could be attributed to several factors: Cyclophosphamide mobilization requires an initial inpatient hospitalization in our institution and often results in re-admissions due to expected toxicity; additionally, the rate of failures, and therefore need for an additional salvage mobilization appears to be much higher with cyclophosphamide; upfront plerixafor was associated with fewer pheresis sessions, and reduced G-CSF use. As many institutions administer cyclophosphamide mobilization on an outpatient basis, it is important to note that the cost benefit of plerixafor upfront remains even if the hospitalization cost of cyclophosphamide mobilization is removed; the cost ratio of cyclophosphamide becomes 1.3 times that of plerixafor. Overall, this single institution study provides, in the context of current clinical practices at MSKCC, the rational for adopting the use of plerixafor as upfront mobilization agent in MM patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Stimulation of Adrenergic Activity By Desipramine Enhances Hematopoietic Stem and Progenitor Cell Mobilization Along with G-CSF in Multiple Myeloma - a Pilot Study of Safety and Efficacy

Blood ◽

10.1182/blood.v126.23.3101.3101 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3101-3101

Author(s):

Aditi Shastri ◽

Ira Braunschweig ◽

Stefan Klaus Barta ◽

Noah Kornblum ◽

Olga Derman ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Adverse Effects ◽

None None ◽

Hematopoietic Stem ◽

Safety And Efficacy ◽

Cd34 Cells ◽

Cell Mobilization ◽

Stem Cell Collection ◽

Stimulation Of

Abstract Background: Hematopoietic stem cell release is regulated by the sympathetic nervous system through the β (3) adrenergic receptor [Mendez-Ferrer et al. Nature 2008]. Peripheral sympathetic nerve neurons express the G-CSF receptor and stimulation of peripheral sympathetic nerve neurons with G-CSF reduced norepinephrine (NE) reuptake significantly, suggesting that G-CSF potentiates the sympathetic tone by increasing NE availability [Lucas et al Blood 2012]. Based on preclinical data, we investigated the NE reuptake inhibitor desipramine in HSC mobilization. Despite augmentation with Plerixafor (CXCR4 inhibitor), 20% of all patients fail to mobilize 6*10^6 CD34 cells/kg in myeloma and the collection rate with G-CSF alone is 51.1% [Diperiso et al Blood 2012]. The cost of upfront plerixafor is $9,081 per patient while desipramine costs $40. We undertook a feasibility study of adult patients with MM undergoing autologous transplantation (ASCT) to study safety and efficacy of mobilization with desipramine and G-CSF. Patients & Methods: From 2013- 2014, 10 patients between the ages of 18-70, eligible for ASCT were enrolled. Desipramine 100mg daily was administered for 7 days, starting 4 days prior to starting G-CSF (D-3) and continue along with G-CSF for a total of 7 days. CBC and CD34 counts were determined on Day+5. If CD34 counts were > 10/ul, stem cell collection was commenced and if < 10/ul, plerixafor was added as salvage therapy. The endpoints were safety and efficacy in mobilizing CD34 cells for ASCT in patients with multiple myeloma. This trial was registered at clinicaltrials.gov as NCT01899326. Results Six of ten patients enrolled completed the protocol and underwent stem cell transplantation. Reasons for not completing were 1. Lack of insurance coverage 2. Non-compliance with study treatment 3. Disease relapse prior to ASCT. Five patients did not have any grade 3 or 4 adverse events and 1 had disease-related Grade 4 hypercalcemia and Grade 2 AKI at the time of stem cell mobilization. No patients had significant treatment related adverse effects. All 6 patients who completed the protocol achieved the target collection of 5*10^6 CD34 cells/kg. Four patients achieved 6*10^6 CD34 cells/kg or more and the remaining 2 patients achieved 5.52 and 5.92 *10^6 CD34 cells/kg respectively. Among the 6 patients, 2 patients received salvage plerixafor. The median time to achieve WBC >1000/ul, ANC >500/ul and platelets>20k was 11.5, 11, 13.5 days Table 1. Age Ind. Regimne Disease status P PB CD34/ul CD34 collected *10^6 / kg Total CD34/kg collected Engraftment (Days to) Adverse effects from desipramine D1 D2 D3 D4 D2 D3 D4 ANC >0.5 Platelets> 20k G1,G2 G3,G4 1 62 Free λ VRD VGPR N 45.8 66.0 7.01 7.01 12 13 none none 2 50 Free λ VRD VGPR N 88.0 143.5 12.22 12.22 12 12 none none 3 58 IgA VCD VGPR N 38.0 67.7 31.6 4.22 2.75 6.97 13 17 none none 4 70 IgAκ VRD VGPR Y 2.40 40.2 16.6 4.31 1.61 5.92 12 14 none none 5 56 IgGκ VCD VGPR Y 8.70 11.9 37.1 19.4 1.33 4.57 1.61 7.51 11 12 none none 6 70 IgGλ VD RD Relapse N 76.2 97.1 5.54 5.54 11 20 AKI hypercalcemia P-Plerixafor; V-Velcade; R-Lenalidomide; D-Dexamethasone; C-Cyclophosphamide Conclusions Overall G-CSF + Desipramine combination appears to be safe, well tolerated and shows signs of efficacy. G-CSF and desipramine was successful in 4/6 (66%) and all achieved the stem cell collection in 2 days or less. Desipramine, GCSF and Plerixafor was successful in all (6/6) patients to achieve a target of 5*10^6 CD34 cells/kg. The mean number of CD34 cells collected in the desipramine+ G-CSF mobilisers was 7.24*10^6 CD34 cells/kg which, based on historical data, is higher than what would be expected with G-CSF alone even though 3/4 of these patients had lenalidomide as induction therapy. Based on these results, a phase II clinical study evaluating the efficacy of G-CSF with desipramine with or without salvage plerixafor in multiple myeloma and lymphoma will be initiated. Disclosures Barta: Seattle Genetics: Research Funding.

Download Full-text