Upfront Plerixafor Plus G-CSF Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma Patients: An Update on Cost Analysis Study at Memorial Sloan Kettering Cancer Center

Abstract Background: Cyclophosphamide plus G-CSF (C+G-CSF) is the most widely used stem cell (SC) mobilization regimen in multiple myeloma (MM) patients. Plerixafor plus G-CSF (P+G-CSF) has demonstrated superior SC mobilization efficacy when compared to G-CSF alone in phase II and III studies and has been shown to rescue patients who fail mobilization with G-CSF with or without cyclophosphamide. Despite the proven efficacy of P+G-CSF in upfront SC mobilization, its use for this indication has been limited, mostly due to concerns of high cost of the drug. Investigators have proposed "on demand" use of plerixafor in patients identified to have inadequate SC mobilization with G-CSF with or without cyclophosphamide, with the assumption that such an approach promotes cost containment by limiting plerixafor use. However, a comprehensive comparison of the cost effectiveness of SC mobilization using C+G-CSF versus P+G-CSF has not been performed. The goal of this retrospective study was to conduct a cost analysis between these two approaches. Methods: Using the pharmacy database, we identified all MM patients treated at Memorial Sloan Kettering Cancer Center between 11/2008 and 6/2012 who received C+G-CSF or P+G-CSF for upfront SC mobilization. Patients collecting <5 x 106 CD34+ cells/kg were considered mobilization failures and had a second attempt at SC mobilization using an alternative approach. For salvage mobilization, patients received P+G-CSF after failing C+G-CSF-based mobilization or were re-mobilized with C+G-CSF along with plerixafor after failing upfront P+G-CSF mobilization. Mobilization costs included in the analysis were those associated with upfront mobilization, those associated with salvage mobilization in patients failing an initial mobilization, and those associated with complications directly related to the mobilization procedures. Cost calculations included the following: cost of cyclophosphamide 3000 mg/m2, plerixafor 0.24 mg/kg, and G-CSF 10 mcg/kg and their administration prior to and during pheresis sessions; pheresis sessions; laboratory tests on pheresis days; re-hospitalization occurring within 15 days of either mobilization approach 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 and costs for 2012. Results: A total of 223 patients undergoing upfront mobilization were identified, with 111 patients receiving C+G-CSF, and 112 patients receiving P+G-CSF. Thirteen patients (12%) were re-hospitalized due to C+G-CSF-related complications, with an average hospital stay of 6.5 days. No patients in the P+G-CSF arm were hospitalized. Nineteen patients (17%) in the C+G-CSF group failed first mobilization and received P+G-CSF as salvage regimen, with four (3.6%) failing salvage collection and ultimately deemed collection failures. Seven patients (6.2%) in the P+G-CSF group failed upfront mobilization and received C+G-CSF along with plerixafor as salvage regimen, with two (1.8%) subsequently failing salvage mobilization. The average number of pheresis sessions performed was 3.29 and 2.42 in the C+G-CSF and P+G-CSF upfront groups, respectively (p=0.373). In total, the average cost of stem cell collection per patient was 1.3 times greater in the C+G-CSF group than in the P+GCSF upfront group (p=0.017). When the costs associated with salvage pheresis are discounted for the 19 patients in the C+G-CSF upfront group who failed first SC mobilization, assuming that these patients could have been salvaged by plerixafor-on-demand, the cost per patient in the C+G-CSF group remains 1.26 times greater (p=0.019) than that of the P+G-CSF group. Conclusion: The use of P+G-CSF upfront for SC mobilization is more cost effective than the more widely used approach employing C+G-CSF. This difference is likely due to several factors including: 1) higher rate of hospitalization in the C+G-CSF group due to expected complications such as febrile neutropenia and catheter-related infections; 2) higher rate of mobilization failure leading to increased need for salvage mobilization in the C+G-CSF group; 3) reduced G-CSF use in the upfront P+G-CSF group. Overall, this single institution study provides additional rationale for the standard use of P+G-CSF as upfront mobilization regimen in MM patients. Disclosures No relevant conflicts of interest to declare.

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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.

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Cost Analysis of Stored Autologous Peripheral Blood Stem Cells for a Second Autologous Transplantation in Multiple Myeloma Patients: A Markov Model

Blood ◽

10.1182/blood.v128.22.1184.1184 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1184-1184

Author(s):

Anca Prica ◽

Vinita Dhir ◽

Nuchanan Areethamsirikul ◽

Christine Chen ◽

Donna Reece ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Cost Analysis ◽

Research Funding ◽

Median Number ◽

Time Period ◽

The Mean ◽

The Cost ◽

Cell Storage

Abstract Background: Autologous stem cell transplantation (ASCT) is a standard part of first-line therapy for pts <70 years of age with multiple myeloma. If remission length is ≥ 2 years, our policy is to offer a salvage transplant upon relapse if the patient is eligible. Many centers, including ours, collect adequate CD34+ cells for two transplantations, as there is concern for poor mobilization post-therapy, including lenalidomide. However, no good data truly quantifies this rate, given plerixafor availability. The advent of novel therapies has reduced the use of second salvage ASCT (ASCT2), and the prolonged storage of cryopreserved stem cells imposes a significant economic burden. We performed a cost analysis to compare the cost of mobilizing and storing stem cells for ASCT2 in all patients versus remobilizing and collecting for ASCT2 upon relapse in eligible patients. Methods: We developed a Markov decision-analytic model to compare the two strategies in a hypothetical cohort of 60 year old patients newly-diagnosed with multiple myeloma. The model simulates the clinical course of 10,000 patients over a 10 year time horizon, with the end point of costs per patient per strategy. Baseline probabilities were derived from published studies as well as analysis of multiple myeloma patients who underwent ASCT1 at Princess Margaret Cancer Centre between January 2003 and December 2012. Key health states include probability of progression (pPD) and death in the 1st 2 years post-ASCT1, pPD >2 years post-transplantation, probability of having an ASCT2 upon relapse vs. a non-ASCT approach. Direct costs were collected from a Canadian public health payer's perspective. Costs were obtained from hospital and provincial databases, as well as the literature and presented in 2016 Canadian dollars. Key costs collected were the cost of mobilization for 2 transplants vs. 1, the cost of remobilization and the cost of stem cell storage. Costs were discounted at 3%. All patients were assumed ASCT2 eligible at relapse. In the re-mobilization arm, all patients were successfully remobilized, with an assumed >50% rate of plerixafor use. Results: 938 patients underwent ASCT1 at Princess Margaret Cancer Centre during this time period, with stem cells stored for a salvage transplant. The mean age of transplanted patients at ASCT1 was 58.4 yrs. The mean number of aphaeresis days required to collect enough cells for 2 stem cell transplants was 1.53 days. The calculated mean aphaeresis days required to collect for 1 transplant was 1.15 days. The median number of bags processed for 2 ASCT was 4, as such, after ASCT1, the median number of bags stored per person was 2. 74 patients (7.9%) underwent ASCT2 over the 10 year period. Most (73%) occurred early, 2-5 yrs post-ASCT1, with only 27% beyond this time period. Over the 10 yr horizon, the total mobilization and storage cost of the stored stem cells strategy was C$9702, versus C$7229 for the re-mobilization strategy, thus storing stem cells for a potential ASCT2 costs an extra C$2473 per patient. Our centre collects such stem cells in >100 pts/yr, at a cost of approximately $250,000. The model was robust to one-way sensitivity analyses of all variables. Storing stem cells only becomes the less costly strategy if the storage costs are less than C$125/6mo or C$10/bag/month (figure 1). Conclusions: The use of salvage ASCT for patients who sustain at least a 2 yr remission with their first is low (less than 10%), and it is associated with significant costs to the system unless the costs of stem cell storage are minimal. With the availability of plerixafor, the cost savings would justify a re-mobilization approach for the minority of patients that are eligible for a salvage ASCT. Figure 1 Figure 1. Disclosures Prica: Janssen: Honoraria; Celgene: Honoraria. Chen:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Research Funding. Reece:Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Novartis: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Trudel:Glaxo Smith Kline: Honoraria, Research Funding; Celgene: Honoraria; Novartis: Honoraria; Oncoethix: Research Funding. Tiedemann:Takeda Oncology: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Amgen: Honoraria; BMS Canada: Honoraria. Kukreti:Celgene: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria.

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Cybord Is An Active, Well Tolerated, Cost-Effective Induction Regimen In Newly Diagnosed Multiple Myeloma – a Single Centre Experience

Blood ◽

10.1182/blood.v122.21.5396.5396 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5396-5396 ◽

Cited By ~ 1

Author(s):

Janusz Krawczyk ◽

Sahar Khan ◽

Bushra Ahsan ◽

Larissa Higgins ◽

Enda McGowan ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Dose Reduction ◽

Conflicts Of Interest ◽

Haematological Toxicity ◽

Cost Effective ◽

Newly Diagnosed ◽

Phase Ii Trials ◽

Post Transplant ◽

Drug Regimens

Abstract Background Based on evidence from clinical trials there is a growing consensus that a three drug regimen involving at least one novel agent (proteasome inhibitor or immunomodulatory drug) should be used as initial induction in patients with newly diagnosed multiple myeloma (NDMM), usually for 3-4 cycles, prior to harvesting stem cells and proceeding to autologous stem cell transplantation (ASCT). Three drug regimens achieve deeper responses both before and after ASCT and this has been shown to translate into superior progression free survival (PFS). CR rates with the three drug regimens prior to ASCT are reported to be in the range of 20-30% with correspondingly high rates of very good partial response (VGPR) (50-60%). One such regimen is the combination of bortezomib with cyclophosphamide and dexamethasone (CyBorD). The published overall response rates (ORR) from phase II trials with CyBorD are approximately 90%, with at least 60% of patients achieving VGPR. At our center, CyBorD has been used as front line therapy since 2008. In this report we present our experience using this regimen as initial therapy in transplant eligible patients. Methods We retrospectively analysed clinical and laboratory records for 31 NDMM patients treated with CyBorD at our institution between 2008 and 2013, all of whom subsequently proceeded to ASCT. The standard protocol consisted of bortezomib 1.3 mg/m2 i.v. twice a week, cyclophosphamide orally at a dose of 300 mg/m2weekly, and dexamethasone orally of 40 mg daily given in 4 days long blocks weekly. Since November 2009 we have also used weekly CyBorD. Results The median age was 57 years (range from 45 to 65), including 24 males and 7 females. According to ISS, 45% patients were classified as stage I, 5% stage II, and 50% as stage III. The ORR was 90% post cycle I and increased to 96% post cycle IV. At least VGPR was observed in 13% of patients after cycle 1 and 56% after cycle IV. Transplantation had improved the responses and 79% had at least VGPR post transplant versus 63% prior, and 24% patients achieved CR post ASCT in comparison to 16% prior ASCT (Fig. 1). The therapy was well tolerated. Haematological adverse events were acceptable and no patient required significant dose reduction or experienced treatment delay due to haematological toxicity. Importantly, no patients developed > grade 3 peripheral neuropathy and no patients required dose reduction or discontinuation of bortezomib due to neurological complications. Stem cell mobilisation was performed using a combination of cyclophosphamide 1.5g/m2 and G-CSF. All patients mobilized successfully without requirement for plerixafor. The medium CD34+ yield after 2 collection days was 8.2 x106/kg (range 1.8 -19.4). The PFS at 2 years was 75% and 64% at three years of follow up. At 2 years post transplant, the patients achieving at least a VGPR had a longer median PFS in comparison to patients with PR (91% vs 76%, p=NS) (Fig. 2). The cost analysis has shown that on average, the drug only cost of 4 cycles of CyBorD was 18 000€. This compares to 38 000€ for 4 cycles of bortezomib, lenalidomide, dexamethasone (VRD). Conclusions Our data confirm the safety and efficacy of the CyBorD protocol and its applicability to routine clinical practice outside of large academic myeloma centres. CyBorD is an active, well tolerated and cost effective option for patients with NDMM, which could be an ideal backbone for the incorporation of new modalities, such as monoclonal antibodies in induction therapy. A randomized comparison with other triple drug regimens are required to fully establish its place in the treatment of newly diagnosed multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

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Autologous Stem Cell Transplant: A Cost Effective and Efficacious Treatment for Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.2358.2358 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2358-2358 ◽

Cited By ~ 3

Author(s):

Seema Niphadkar ◽

Indumathy Varadarajan ◽

Tiffany Pompa ◽

Kevin Y Hou ◽

Kathleen Degen ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Maintenance Therapy ◽

Progression Free Survival ◽

Cost Effective ◽

Novel Agents ◽

Newly Diagnosed ◽

Free Survival ◽

Optimal Duration ◽

The Cost

Abstract Background: Induction chemotherapy followed by autologous stem cell transplantation (ASCT) is considered a standard of care for appropriate patients with newly diagnosed multiple myeloma (MM), but with the rapid expansion of available treatments, the role of ASCT has been questioned. Numerous studies have shown an improvement in complete response (CR) and progression free survival (PFS) with ASCT but our study is a cost comparison between novel agents and ASCT. We aimed to compare the cost effectiveness of ASCT versus non-transplant regimens in relation to PFS. Methods: We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) between 2008 and 2013 using the ICD-9 code 203.00 for MM and V42.81 for ASCT in the primary and secondary diagnosis fields. The analysis included patients who were 18 years or older. We monitored the trends in ASCT with regards to cost of a transplant admission and length of stay (LOS). Cost of hospitalization was adjusted for inflation in reference to the year 2011 and cost to charge ratio. Literature regarding common treatment regimens, response rates, duration of treatment, and PFS was reviewed. The assumption was made that transplant eligible patients that did not undergo transplant would be treated as though they were transplant ineligible. Gay et al 2015 showed a 43.4-month (mo) median PFS with 4 cycles of Rd followed by ASCT and lenalidomide maintenance until progression or toxicity. The cost of novel regimens was estimated using the one month commercial cost described by Roy et al and wholesale acquisition costs for new agents not described by the study which were adjusted using adjunct cost described by the study. A standard weight of 70 kg was used for agents requiring dose calculations. The cost of novel agents for an equivalent duration of 43.4 mo was estimated. Results: A total of 44778 (weighted n=9039) hospitalizations for MM (Male 55.9%, Caucasian 57.9%, peak incidence 65-79 yrs) occurred from 2008-2013. The average length of stay during ASCT admission was 11.4 +/- 0.4 days with a cost of $109,856 +/-5749.83. There has been a 16.89% decrease in LOS and 1.99% increase in the cost of ASCT (p<0.05). Gay et al showed a 43.4 mo PFS with 4 cycles Rd ($46,216) followed by ASCT ($109,856) and lenalidomide maintenance (~35.4 mo $564,453 adjusted for cost of office visits and lab work) for a total of $720,525 Conclusion: Rd + ASCT + R maintenance is efficacious for the treatment of newly diagnosed MM. The cost associated with the induction and transplant represents only 22% of the total cost, whereas lenalidomide maintenance makes up 78%. Considering secondary risks and the cost involved with lenolidomide maintenance, further investigation is warranted regarding the optimal duration of maintenance therapy and resultant progression free survival. It also raises the need for alternative options for maintenance therapy. Bortezomib and ixazomib are both more cost effective options and studies are in progress to assess their efficacy in PFS in the maintenance setting. Studies using novel agents for induction prior to ASCT are ongoing and have yet to reach an optimal duration of therapy. Table 1 shows that most of the novel agents used in combination regimens are more expensive that ASCT. Although most patients would not remain on one of these regimens for 43.4 mo, they would presumably progress through multiple lines of therapy during the 43.4 mo of PFS that ASCT provides. In an era of cost consciousness, ASCT should continue to be an integral component of MM treatment. Disclosures No relevant conflicts of interest to declare.

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Cost Analysis of the Use of Voriconazole, Posaconazole and Micafungin in the Primary Prophylaxis of Invasive Fungal Infections in Recipients of Allogeneic Hematopoietic Stem Cell Transplants

Journal of Health Economics and Outcomes Research ◽

10.36469/9832 ◽

2015 ◽

Vol 3 (2) ◽

pp. 153-161

Author(s):

Santiago Grau ◽

Carlos Solano ◽

Carol García-Vidal ◽

Isidro Jarque ◽

Jon A. Barrueta ◽

...

Keyword(s):

Stem Cell ◽

Cost Analysis ◽

Hematopoietic Stem Cell ◽

Fungal Infections ◽

Primary Prophylaxis ◽

Antifungal Prophylaxis ◽

Invasive Fungal Infections ◽

Efficacy Rate ◽

Hematopoietic Stem ◽

The Cost

Objectives: Compare the cost of the primary prophylaxis of invasive fungal infections (IFI) with voriconazole, posaconazole, and micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) in hospitals of the National Health System (NHS) in Spain. Methods: A cost analysis was made for 100 days and 180 days of prophylaxis and a decision tree model was developed. The efficacy rate of IFI prophylaxis and survival rate with liposomal amphotericin B treatment of prophylaxis failures were obtained from randomized trials and a meta-analysis of mixed treatment comparisons. The model simulation was interrupted with IFI treatment (prophylaxis failures). The costs of medication and its intravenous administration in the hospital (in the case of micafungin) were considered. Results: In the non-modeled analysis, the savings per patient of prophylaxis with voriconazole ranged from €1,709 to €9,655 compared with posaconazole oral solution, from €1,811 to €9,767 compared with posaconazole gastro-resistant tablets and from €3,376 to €7,713 compared with micafungin. In the modeled analysis, the mean cost per patient of the prophylaxis and treatment of IFIs was €6,987 to €7,619 with voriconazole, €7,749 with posaconazole, and €22,424 with micafungin. Therefore, the savings per patient of prophylaxis with voriconazole was €130 to €3,664 and €11,132 to €30,374 compared with posaconazole and micafungin, respectively. The result remained stable after modification of the number of days of antifungal prophylaxis and the cost of antifungal treatment of failures. Conclusion: Taking into account this model, antifungal prophylaxis with voriconazole in recipients of hematopoietic progenitor transplants, compared with posaconazole or micafungin, may represent savings for hospitals in Spain.

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Optimization of Plerixafor Utilization Based on Peripheral Blood CD34+ Count for Autologous Peripheral Blood Stem-Cell Collection

Blood ◽

10.1182/blood-2020-140171 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 41-41

Author(s):

Gaurav K. Gupta ◽

Sera Perreault ◽

Stuart Seropian ◽

Christopher A. Tormey ◽

Jeanne E. Hendrickson

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Medical Center ◽

Tertiary Care ◽

Peripheral Blood Cd34 ◽

Tertiary Care Medical Center ◽

Group 2 ◽

Group 1

Introduction: Peripheral CD34+ cells may be mobilized using filgrastim (G-CSF) alone or in combination with chemotherapy. However, some patients also require plerixafor, an inhibitor of C-X-C chemokine receptor type-4, for adequate mobilization. Given its cost, judicious utilization of plerixafor is warranted. Material and Methods: A retrospective analysis of autologous stem-cell mobilization was performed at a tertiary-care medical center in adult patients with multiple myeloma and lymphoma; here we will focus on the utility of repeat plerixafor dosing. Patients were mobilized at the treating physician's discretion with filgrastim plus plerixafor or chemotherapy plus filgrastim plus plerixafor. Collections were initiated once peripheral CD34+ counts reached 20/µL (or 10/µL if chemotherapy mobilized); plerixafor was administered if these counts were not reached after 4 or 8 days, respectively, of filgrastim treatment. Results: Patients with multiple myeloma (86) or lymphoma (30) were evaluated. One hundred five were mobilized by filgrastim plus plerixafor and 11 by chemotherapy plus filgrastim plus plerixafor. No patient that received plerixafor with a CD34+ count <5/µL after chemotherapy mobilized the next day. The end collection goal was achieved in 86 (81.9%) of the filgrastim plus plerixafor group and 7 (63.6%) of the chemotherapy plus filgrastim plus plerixafor group. Patients given at least one dose of plerixafor were divided into groups based on collection goal, peripheral blood CD34+ cell count after 1 dose and the first day collection yield: Group 1) Goal of 3x10^6/kg and CD34+ count ≥ 30 cell/µL vs < 30 cell/µL; Group 2) Goal of 6x10^6/kg and ≥ 50% of collection goal after 1 day of collection vs CD34+ count < 50 cell/µL or < 50% of collection goal. Forty of 42 (95%) patients in Group 1 with a CD34+ count ≥ 30 cell/µL achieved their end collection goal after one plerixafor dose. Eighteen of 19 (95%) patients in Group 1 with a CD34+ count <30 cell/µL received a second dose of plerixafor and 8 (44.4%) achieved their end collection goal. Twenty-eight of 32 (87.5%) patients in Group 2 with ≥ 50% of collection goal achieved on the first day of collection reached their end collection goal after one plerixafor dose. Nine of 12 (75%) patients in Group 2 with a CD34+ count of < 50 cells/µL or <50% collection goal received an additional dose of plerixafor and 6 (66.7%) achieved their end collection goal. Conclusion: Based on these data, we have developed the following repeat plerixafor dosing algorithm: 1) for a collection goal is 3x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is < 30 cell/µL, and 2) for a collection goal of 6x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is < 50 cell/µL or if the first day of collection yields <50% of the end goal. This algorithm optimizes pharmacy, apheresis and stem cell processing resources. Disclosures No relevant conflicts of interest to declare.

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Cost-effective Analysis of Proton Pump Inhibitors in Long-term Management of Gastroesophageal Reflux Disease: A Narrative Review

Hospital Pharmacy ◽

10.1177/0018578719893378 ◽

2019 ◽

Vol 55 (5) ◽

pp. 292-305

Author(s):

Shazia Jamshed ◽

Akshaya Srikanth Bhagavathula ◽

Sheikh Muhammad Zeeshan Qadar ◽

Umaira Alauddin ◽

Sana Shamim ◽

...

Keyword(s):

Cost Effectiveness ◽

Gastroesophageal Reflux Disease ◽

Cost Effective ◽

The Other ◽

Cost Effectiveness Ratio ◽

On Demand ◽

Step Down ◽

The Cost ◽

Term Management

Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder that results from regurgitation of acid from the stomach into the esophagus. Treatment available for GERD includes lifestyle changes, antacids, histamine-2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), and anti-reflux surgery. Aim: The aim of this review is to assess the cost-effectiveness of the use of PPIs in the long-term management of patients with GERD. Method: We searched in PubMed to identify related original articles with close consideration based on inclusion and exclusion criteria to choose the best studies for this narrative review. The first section compares the cost-effectiveness of PPIs with H2RAs in long-term heartburn management. The other sections shall only discuss the cost-effectiveness of PPIs in 5 different strategies, namely, continuous (step-up, step-down, and maintenance), on-demand, and intermittent therapies. Results: Of 55 articles published, 10 studies published from 2000 to 2015 were included. Overall, PPIs are more effective in relieving heartburn in comparison with ranitidine. The use of PPIs in managing heartburn in long-term consumption of nonsteroidal anti-inflammatory drug (NSAID) has higher cost compared with H2RA. However, if the decision-maker is willing to pay more than US$174 788.60 per extra quality-adjusted life year (QALY), then the optimal strategy is traditional NSAID (tNSAID) and PPIs. The probability of being cost-effective was also highest for NSAID and PPI co-therapy users. On-demand PPI treatment strategy showed dominant with an incremental cost-effectiveness ratio of US$2197 per QALY gained and was most effective and cost saving compared with all the other treatments. The average cost-effectiveness ratio was lower for rabeprazole therapy than for ranitidine therapy. Conclusion: Our review revealed that long-term treatment with PPIs is effective but costly. To achieve long-term cost-effective approach, we recommend on-demand approach to treat heartburn symptoms, but if the symptoms persist, treatment with continuous step-down therapy should be applied.

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Is the platelet-to-lymphocyte ratio a new prognostic marker in multiple myeloma?

Journal of Laboratory Physicians ◽

10.4103/jlp.jlp_36_18 ◽

2018 ◽

Vol 10 (04) ◽

pp. 363-369 ◽

Cited By ~ 1

Author(s):

Serife Solmaz ◽

Ozcan Uzun ◽

Celal Acar ◽

Omur Gokmen Sevindik ◽

Ozden Piskin ◽

...

Keyword(s):

Multiple Myeloma ◽

Negative Impact ◽

Progression Free Survival ◽

Cost Effective ◽

P Value ◽

Platelet To Lymphocyte Ratio ◽

Cox Models ◽

Lymphocyte Ratio ◽

Kaplan Meier ◽

The Cost

ABSTRACT BACKGROUND: Recent reports showed neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. MATERIALS AND METHODS: We retrospectively examined the PLR, NLR, and MLR in a cohort of 186 newly diagnosed multiple myeloma (MM) patients. This study investigated the prognostic relevance of NLR, PLR, and MLR in MM patients. NLR, PLR, and MLR were calculated from whole blood counts before therapy. The Kaplan–Meier curves and multivariate Cox models were used for the evaluation of survival. RESULTS: Applying cutoff of 1.9 (NLR), 120.00 (PLR), and 0.27 (MLR), decreased PLR showed a negative impact on the outcome. Decreased PLR is an independent predictor for PFS and OS. There were no significant differences in median survival between the high and low NLR (P = 0.80) and MLR (P = 0.87) groups. CONCLUSIONS: In this study, thrombocytopenia and low PLR are associated with poor survival in MM patients does this P value apply to thrombocytopenia or low PLR and may serve as the cost-effective prognostic biomarker.

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EPOCH-F: A Novel Salvage Regimen for Multiple Myeloma Prior to Reduced-Intensity Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v112.11.4328.4328 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4328-4328

Author(s):

Saad Jamshed ◽

Daniel Fowler ◽

Sattva Neelapu ◽

Robert M. Dean ◽

Seth M Steinberg ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Chronic Gvhd ◽

Cd4 Count ◽

Salvage Regimen ◽

Chemotherapeutic Regimen ◽

Reduced Intensity

Abstract Variation in baseline host immune status contributes to inconsistent donor engraftment and may impede maximal graft-versus-myeloma effects after reduced-intensity allogeneic stem cell transplantation (RI-alloSCT) for advanced multiple myeloma. We performed a phase II study to determine the efficacy of a novel salvage regimen, EPOCH-F, which was designed to provide immune depletion and disease control prior to RI-alloSCT, in 22 patients with advanced multiple myeloma. EPOCH is an infusional chemotherapeutic regimen consisting of etoposide, vincristine and adriamycin, with prednisone, cyclophosphamide and fludarabine and given in 21 day cycles prior to RI-alloSCT. Patients received at least 1 and no more than 5 cycles of EPOCH-F gudied by peripheral blood CD4+ T cell count. Pts achieving adequate lymphodepletion proceeded to RI-alloSCT; otherwise patients proceeded to RI-alloSCT after 5 cycles or if there was disease progression during EPOCH-F, regardless of CD4 count. Median age was 53 years (range, 36–65); median time from initial therapy to transplant was 12 months (range, 2–168). Median number of prior therapies was 2 (range, 1–8), while 63% had chemotherapy sensitive disease. 68% of patients had received a novel agent. Patients received a median of 3 cycles (range, 1–5) of EPOCH-F. Therapy was well tolerated with manageable toxicities, mostly hematologic. Neutropenia (grade IV) was the most common toxicity seen in 77% of the administered cycles with only 6 episodes of neutropenic fever. Median lymphocyte count decreased from 1423/μL (range, 335–2788) to 519/μL (range, 102–1420); CD4 count decreased from 320/μL (range, 130–1366) to 115/μL (range, 30–309). In 21 evaluable patients, the overall response rate to EPOCH-F was 22% and 68% had stable disease. 13% of patients achieved CR/nCR. Only 1 patient progressed while on therapy. 20 patients received allograft from HLA matched sibling donors and were evaluable for engraftment. Median Day 100 chimerism was 100% (range 60–100, mean 95). 70% of patients achieved ≥VGPR including CR/nCR, while CR/nCR was seen in 40% of the patients. Median overall survival was 46.1 months. 10 (50%) patients are currently alive. Acute GVHD (grade II–IV) was seen in 47% and chronic GVHD (grade III–IV) was seen in 52% of patients. Treatment-related mortality at 100 days was 5% and 30% at 60 months. EPOCH-F is an active regimen which facilitates consistent and rapid full donor engraftment following RI-alloHSCT from related donors in patients with advanced multiple myeloma.

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VAMP/ThaCyDex: Velcade® (Bortezomib), Adriamycin, Melphalan and Prednisone Alternating with Thalidomide, Cyclophosphamide and Dexametasone as a Salvage Regimen in Relapsed Multiple Myeloma Patients

Blood ◽

10.1182/blood.v112.11.3694.3694 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3694-3694 ◽

Cited By ~ 1

Author(s):

Enrique Colado ◽

Maria-Victoria Mateos ◽

Maria-Jose Moreno ◽

Felipe de Arriba ◽

Javier de la Rubia ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Complete Response ◽

Treatment Schedule ◽

Salvage Regimen ◽

Peripheral Polyneuropathy ◽

Highly Effective

Abstract Background: Bortezomib and Thalidomide have demonstrated to be effective in relapsed and refractory Multiple Myeloma (MM) patients, including those with adverse cytogenetics (CG). Moreover, Bortezomib and thalidomide-based combinations result attractive to improve efficacy, but toxicity could be increased. Based on this background, we have tested if an alternating regimen consisting on two highly effective schedules could overcome MM drug resistance without an increase in toxicity in relapsed/refractory MM patients. Patients and Methods: Treatment schedule consisted on 6 alternating cycles of VAMP (Bortezomib 1,3mg/msq IV days 1,4,8 and 11; Melphalan, 9mg/msq po, days 1–4; Prednisone 60mg/msq po, days 1–4; and conventional or liposomal Adriamycin 40 or 30mg/msq respectively on day 1 of a 28 day cycle) alternating with ThaCyDex (Thalidomide 200mg/d po day 1–28; Cyclophosphamide 50mg/d po, days 1–28; and Dexametasone 40mg/d po, days 1–4). After 6 cycles, responding patients, received the previous schedule, every other month as consolidation therapy. Results: From June 2007 until August 2008, 20 patients have been included, with a median age of 63 years (Range 48–81); 15 patients (75%) had previously received autologous stem cell transplantation. 6 patients (30%) had previously received Bortezomib-based therapy, and one patient (5%) had previously received IMID-based therapy. Efficacy and toxicity were evaluated on an intent-to-treat basis. After a median of 6 cycles, 20 patients were evaluable for response, 9 patients (42%) achieved immunofixation negative Complete Response (CR), 3 patients (16%) nCR, 9 patients (47%) partial response, which makes an ORR of 94,7%. In addition, 1 patient (5%) remained in stable disease and one patient died during induction therapy due to septic shock. Seven patients presented high risk cytogenetic abnormalities [t(4;14) and/or delRB], and CR was obtained in 3 of them (42%) plus one additional nCR in 1 patient (14%). Moreover, allogeneic stem cell transplantation was performed in two of these high risk patients, as they were effectively rescued by this salvage regimen. Two patients progressed during the consolidation treatment. Toxicity was manageable, being haematologic events the most frequently reported. 6 patients (30%) developed ≥G3 thrombocytopenia and 6 patients (30%) neutropenia. Infection ≥G3 occurred in 3 patients (16%). Despite the combination of two drugs with potential neurologic toxicity, the use of them in alternated schedule resulted in that only 3 patients (15%) developed Peripheral Polyneuropathy, none of them >G2. Conclusion: Preliminary results show that alternating VAMP/ThaCyDex is a highly effective salvage regimen in relapsed/refractory MM patients, including high risk subgroup with adverse cytogenetic abnomalities. Haematologic toxicity was the most frequent adverse event, while the incidence of Peripheral Polyneuropathy was low, despite the use of two neurotoxic drugs. This results indicate that the alternating approach allows the exposure to a large number of active drugs without increase in the toxicity. A second analysis will be performed in December 2008 and results will be updated.

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