The More Effective and the More (bio) Similar: Plerixafor and Filgrastim XM02 (tevagastrim) As First Line PBSC Mobilization Strategy in Patients with Multiple Myeloma and Lymphomas Candidate to ABMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2994-2994
Author(s):  
Daniele Laszlo ◽  
Giovanna Andreola ◽  
Aleksandra Babic ◽  
Mara Negri ◽  
Cristina Rabascio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
European Medicines Agency ◽  
High Dose ◽  
First Line ◽  
Adequate Number ◽  
Cd34 Cells

Abstract Abstract 2994 Patients affected by hematologic malignancies might benefit from high dose chemotherapy followed by peripheral stem cells (PBSC) transplant. Chemotherapy in combination with G-CSF is effective in mobilizing stem cells but often toxic, might require prolonged hospitalization and extensive supportive care. Moreover a high proportion of patients, ranging from 11 to 53%, fail to collect an adequate number of stem cells with this approach. In this setting plerixafor, a CXCR4 chemokine antagonist, has shown to increase the number of circulating CD34+ cells in cancer patients when used alone or with G-CSF and to be able to rescue patients unable to mobilize with traditional regimens. Recently, several forms of biosimilar nonglycosylated recombinant human G-CSF have been clinically developed and approved by the European Medicines Agency for the same indications as the reference filgrastim product on the basis of comparable quality, efficacy, and safety. Biosimilars also provide a more cost-effective strategy and their use in clinical setting may provide cost savings in their indicated uses. From December 2010 to July 2011, 16 patients, median age 55 (19–67), affected by Non-Hodgking Lymphoma (6), Hodgking Disease (2) and MM (8), received a combination of biosimilar version of G-CSF (Tevagrastim) and plerixafor in order to mobilize PBSC as first line strategy. Tevagrastim was self-administered (10μg/kg/die) for 3 days; on day 4 patients were admitted to the hospital, circulating CD34+ cells counted and if >20 cells/μl, plerixafor was administered (0.24mg/kg) 12 hours before the scheduled apheresis. There were 7 males and 9 females, median lines of previous chemotherapy was 1(1–4). Median number of circulating CD34+ cells on day 4 was 16 (8–42). Plerixafor was administered to all but 1 patients who had already 42 CD34+ cells/μl on day 4. On day 5, after plerixafor administration median number of circulating CD34+ cells had raised to 68/μl (18–138). All the patients underwent leukapheresis and were able to collect an adequate number of CD34+ cells necessary for the transplantation procedure with a median number of 5.2 ×106 (2.2–10.6) CD34+cells/kg in a median number of 1 procedure (1–2). For patients with Multiple Myeloma, 6/8 patients were able to collect a median of 5.8×106 CD34+/kg (4.2–10.6) in a single procedure. No major side effect was observed. So far, 7/16 patients underwent high dose chemotherapy followed by PBSC transplant. Engraftment occurred in all patients with a time to ANC>500 of 12 (9–13) and of PLT>20.000 of 13 (9–19) days. The combination of tevagrastim and plerixafor is safe and effective in mobilizing PBSC and allows a collection of a more than adequate number of cells in most of the patients in a maximum of 2 apheresis procedure, even in patients with MM who need to collect a double amount cells. Disclosures: No relevant conflicts of interest to declare.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

Cell-Freezing Devices Are Not Strictly Needed to Start an Autologous Hematopoietic Transplantation Program: Non-Cryopreserved Peripheral Blood Stem Cells Can be Used to Restore Hematopoiesis after High Dose Chemotherapy: A Multicenter Experience in 268 Autografts in Patients with Multiple Myeloma or Lymphoma. Study on Behalf of the Latin-American Bone Marrow Transplantation Group (LABMT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 849-849 ◽  
Author(s):  
Amado J Karduss-Urueta ◽  
Guillermo J. Ruiz-Arguelles ◽  
Rosendo Perez ◽  
Guillermo J Ruiz-Delgado ◽  
Angelica Maria Cardona ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Median Time ◽  
Latin American ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Transplantation Program ◽  
Blood Stem Cells

Abstract Storage of peripheral blood stem cells (PBSC) at 4ºC is a simple and inexpensive alternative to cryopreservation for preserving the clonogenic capacity of progenitors cells in the autologous transplant setting, however it has been perceived as unsafe and has deserved little attention. We present the experience of two Latin-American centers using refrigerated, non-cryopreserved stem cells after conditioning with high dose melphalan, CBV or BEAM in a large group of lymphoma and myeloma patients Materials and Methods PBSC were mobilized with filgrastim 5 mg/kg/BID for three to six days.One to three apheresis procedure were employed; the cells were stored at 4ºC for 5 to 6 days in patients who received BEAM or CBV and for 3 days in those given melphalan. All of the conditioning regimens were administered preserving the full intensity of dose (Table 1). After the autograft all patients received filgrastim or pegfilgrastim Table 1 BEAM D-5 D-4 D-3 D-2 D-1 BiCNU 300 mgs/m2 X Etoposide 200-400 mgs/m2 X X X X Citarabine 300-400 mgs/m2 X X X Melphalan 140 mgs/m2 X CBV BiCNU 300 mgs/m2 13 patients received carboplatin 900 mgs/m2 instead BiCNU X Etoposide 300 mgs/m2 X X X Ciclophosphamide 2.000 mgs/m2 X X X Melphalan Melphalan 200 mgs/m2 X Melphalan 100 mgs/m2 X X Results 102 lymphoma patients: 48 Hodgkin`s lymphoma (HL) and 54 non-Hodgkin´s lymphoma (NHL) received BEAM (71) or CBV (31). A median of 3.3 millions/kg of CD34 was infused; the median viability of the cells after 5-6 days of refrigeration (trypan blue exclusion) was 82%. 101 out of 102 patients engrafted, median time to achieve 500/ul neutrophil or more was 12 days, 100 were evaluable for thrombopoiesis, 99 of them had a self- sustained platelet count of 20.000 or more at a median of 17 days. The OS at 5 years was 59% and 42% for patients with Hodgkin and lymphoma respectively 151 patients with multiple myeloma received melphalan 200 mgs/m2. After 72 hours of refrigeration, a median of 2.6 millions/kg of CD34 cells were infused, the viability in all cases being > 90%. Three patients were not evaluable because early death. Median time to achieve 500 neutrophil or more and 20.000 platelets was 12 (9-50) and 15 (7-50) days. The OS at 5 years was 50% 21 patients with NHL and HL received as conditioning regimen melphalan 200 mgs/m2. After 72 hours of storage, a median of 1.75 millions/kg of CD34 cells were transplanted, 100% of them engrafted, median time to 500 neutrophils and 20.000 platelets was 11.9 and 15 days respectively There were no cases of secondary engraftment failure in any of the three groups Conclusion In this series of 268 patients, we have shown that autologous PBSC can be kept at 4ºC in a conventional blood bank refrigerator for up to six days and use them to rescue high-dose chemotherapy in both multiple myeloma and lymphoma patients. Avoiding freezing procedures results in substantial cost savings. The availability of freezing devices for hematopoietic stem cells is not anymore an obstacle to start a an autologous transplantation program This observation is critical in areas of underprivileged economic circumstances, where more than 50% of the inhabitants of the world live. Disclosures No relevant conflicts of interest to declare.

Pegfilgrastim Versus Filgrastim To Accelerate Hematopoietic Recovery after High Dose Melphalan and Autologous Hematopoietic Stem Cell Transplant (ASCT) for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5193-5193
Author(s):  
Rebecca L. Olin ◽  
Selina M. Luger ◽  
David L. Porter ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cohort Study ◽  
Stem Cell ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Median Number ◽  
High Dose ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
High Dose Melphalan

Abstract High-dose melphalan followed by ASCT is a common component of the early treatment for patients with multiple myeloma. Daily subcutaneous injections of filgrastim (Neupogen) at 5 ug/kg/day until ANC > 500/ul are routinely administered at our center from day +4 following ASCT, in order to accelerate hematopoietic recovery and lessen neutropenic complications. Pegfilgrastim (Neulasta) as a single 6 mg fixed dose subcutaneous injection has been shown to have similar efficacy and ease of use when compared to filgrastim in the non-transplant setting, but little data is available in the transplant setting. We began using pegfilgrastim day +1 following ASCT for patients with multiple myeloma and performed a retrospective cohort study comparing those who received filgrastim (n=6) with those who received pegfilgrastim (n=11). Transplants occurred between July 2002 and January 2004 and included all patients transplanted for myeloma in that time period for whom sufficient data was available. All patients had at least 2 x 106 CD34+ cells/kg peripheral stem cells harvested after cytoxan and filgrastim mobilization. Main outcome measures were: days from stem cell infusion to WBC nadir, days to ANC>500/ul, and days to ANC>1000/ul. Subjects were excluded if CBCs were drawn less frequently than every four days. There were no significant differences between the filgrastim and pegfilgrastim groups with respect to the following demographic variables: age, gender, hemoglobin, creatinine, calcium, albumin and beta-2 microglobulin at diagnosis. The groups were also balanced with respect to SPEP, UPEP, presence of lytic lesions and number of prior lines of therapy. The median number of CD34+ cells infused was similar: 5.7 x 106 in the filgrastim group vs 4.8 x 106 in the pegfilgrastim group (p=0.28). After transplant, median number of days to WBC nadir in the filgrastim group (FG) was 7 (range 5–9) vs 6 (range 5–8) in the pegfilgrastim group (PG) (p=0.31). However, median number of days to ANC>500/ul in the FG was 11.5 (range 11–17) vs 10 (range 9–12) for PG (p=0.02). Similarly, median number of days to ANC>1000/ul was 12 (range 11–17) for FG vs 11 (range 10–13) for PG (p=0.03). Five of six patients in the FG had neutropenic fever after transplant, compared to five of eleven patients in the PG (p=0.30). Currently, no significant differences in infection or relapse rates between groups have been noted and there were no deaths in either group. In this retrospective cohort study, pegfilgrastim was safe and at least equivalent to filgrastim for accelerating hematopoiesis after ASCT for multiple myeloma. Furthermore, there was no significant difference in the incidence of neutropenic fever, infection and survival, suggesting a similar clinical utility.

Incidence of Febrile Episodes During Stem Cells Mobilization After High Dose Cyclophosphamide Chemotherapy and G-CSF (filgrastim or lenograstim) Administration in Multiple Myeloma Patients: Preliminary Final Results.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4560-4560
Author(s):  
Enrico Orciuolo ◽  
Gabriele Buda ◽  
Emerenziana Marturano ◽  
Elisa Mauro ◽  
Giuseppe Milone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Treatment Plan ◽  
High Dose ◽  
Absolute Count ◽  
Functional Block ◽  
Grade 3 ◽  
Febrile Episodes

Abstract Abstract 4560 Introduction The G-CSF, primary regulator of granulopoiesis, has shown its efficacy in reducing duration of neutropenia after chemotherapy or myelosuppressive therapy. In these situations G-CSF, accelerating the granulocytous reconstitution, may enable a significant reduction of the incidence, duration and severity of infection. Commercially formulations of rHu-G-CSF include lenograstim, a glycosylated form, and filgrastim, a non-glycosylated form. Glycosylation of the molecule contribute to pharmacokynetis advantages and to higher affinity to specific receptor. Additionally, lenograstim exposed neutrophils maintain unchanged all their functions in vitro, while filgrastim exposed neutrophils present functional defects due to higher adhesivity, cytoscheletric alterations and a more immature phenotype. Aim On these bases, we hypotized that lenograstim may prevent febrile episodes (FE) and reduce their lasting in patients with chemotherapy derived neutropenia more efficiently than filgrastim. Primary endpoint is the incidence of FE (ClinicalTrials.gov ID: NCT00932217). Patients and methods starting from April 2005, 180 multiple myeloma patients achieving high dose cyclophosphamide for stem cells mobilization were enrolled in 11 Italian Centers. Treatment plan consisted in: high dose cyclophosphamide (3 or 4 g/sqm) on day 1, G-CSF (random 1:1 on the base of a generated random list: filgrastim or lenograstim) 30 MU/day from day +4 to +9, 60 MU/day from day +10 to the achievement of an optimal CD34+ cell count for staminoapheresis. FE, significant if equal or higher than 38 °C for at least 2 different determinations, were recorded till day +30. Results 176 of 180 patients received scheduled treatment and are eligible for final analyses. All 176 patients underwent post-chemo grade 4 neutropenia and G-CSF was administered starting from day +4. FE were recorded in 26 pts, 16 in the filgrastim arm (89 total patients) and 10 in the lenograstim arm (87 total patients). The global fever incidence was 14.77%, 17.98% with filgrastim and 11.49% with lenograstim. However, to demonstrate functional block of filgrastim exposed neutrophils, FE have been related to neutrophil absolute count. Related to the neutropenia grade, 8 FE are recorded with filgrastim (8.99%) and 1 FE with lenograstim (1.15%) with absolute neutrophil count >500/μL (grade 3) (chi square test with Yates' correction: p=0.0436); this difference is still evident when neutrophils are >1000/μL (grade 2), with 7 episodes with filgrastim (7.87%) versus 1 (1.15%) with lenograstim. Conclusions Lenograstim is associated with a reduced global incidence of FE in multiple myeloma patients undergoing to high dose cyclophosphamide and stem cells mobilization when compared to filgrastim. Additionally, excluding the time frame when neutrophils are not yet recovered (neutrophils <500/μL; grade 4 neutropenia) and G-CSF effects may not be demonstrated, filgrastim treated patients present, when compared to lenograstim treated patients, an higher FE incidence at neutrophil absolute count recovery (both with grade 3 and grade 2 neutropenia), confirming the functional block of filgrastim exposed neutrophils described in vitro. On the contrary, lenograstim allows to recovery normally functional neutrophils as demonstrated by the very low incidence of FE (1.15% with neutrophils >500/μL) in treated patients. Disclosures: No relevant conflicts of interest to declare.

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

A Comparison of Chemotherapy + G-CSF Versus Plerixafor (Mozobil®) + G-CSF for Stem Cell Mobilization In Patients with Multiple Myeloma Treated with Lenalidomide

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2258-2258
Author(s):  
Tomer M Mark ◽  
Adriana C Rossi ◽  
Roger N Pearse ◽  
Morton Coleman ◽  
David Bernstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Yield ◽  
High Dose ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Stem Cell Collection

Abstract Abstract 2258 Background: Prior use of lenalidomide beyond 6 cycles of therapy in the treatment of multiple myeloma (MM) has been shown to negatively impact stem cell yield, but this phenomenon can be overcome with the addition of high-dose cyclophosphamide to standard G-CSF mobilization. We hypothesized that the use of plerixafor (Mozobil®) would compare similarly to chemotherapy in rescuing the ability to collect stem cells in lenalidomide-treated myeloma. Methods: We performed a retrospective study comparing the efficacy of plerixafor + G-CSF mobilization (PG) to chemotherapy + G-CSF (CG) (either high-dose cyclophosphamide at 3g/m2 or DCEP [4-day infusional dexamethasone/ cyclophosphamide/ etoposide/cisplatin]) in 49 consecutive stem cell collection attempts in patients with MM exposed to prior lenalidomide. The primary endpoint was the ability to collect sufficient stem cells for at least two transplants (minimum 5×106 CD34+ cells/kg), comparing results in terms of total exposure to lenalidomide and time elapsed from lenalidomide exposure until the mobilization attempt. The secondary endpoint was number of apheresis days required to meet collection goal. Resilts: Twenty-four patients underwent PG mobilization and twenty-five with CG (21 with G-CSF + cyclophosphamide, 4 with G-CSF+DCEP). The two groups did not differ in terms of total amount of lenalidomide exposure: median number of lenalidomide cycles for patients mobilized with PG was 6.5 (range 1.2–86.6), vs. 6 (range 2–21.6), for patients mobilized with CG (P = 0.663). The median time between mobilization and last lenalidomide dose was also similar between the two groups: 57.5 (range 12–462) days for PG vs. 154 (range 27–805) days for CG (P = 0.101). There was an equivalent rate of successful collection of 100% for PG and 96% for CG, P = 0.322. One patient failed collection in the CG group due to emergent hospitalization for septic shock during a period of neutropenia; no patient collected with PG had a serious adverse event that interrupted the collection process. Stem cell yield did not differ between the two arms (13.9 vs. 18.8 × 106 million CD34+ cells/kg for PG vs. CG respectively, P = 0.083). Average time to collection goal was also equal, with a median of time of 1 day required in both groups, (range 1–2 days for PG, 1–5 days for CG, P = 0.073). There was no relationship between amount of lenalidomide exposure and stem cell yield with either PG (P = 0.243) or CG (P = 0.867). Conclusion: A plerixafor + G-CSF mobilization schedule is equivalent in efficacy to chemotherapy + G-CSF in obtaining adequate numbers of stem cells for two autologous stem cell transplants in patients with MM exposed to lenalidomide; however, PG may be a less toxic approach than chemomobilization. Number of lenalidomide cycles has no impact on chances of stem cell collection success using either method. Disclosures: Mark: Celgene Corp: Speakers Bureau; Millenium Corp: Speakers Bureau. Zafar: Celgene Corp: Speakers Bureau. Niesvizky: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding.

Bendamustine, Bortezomib and Dexamethasone (BBD) As First-Line Treatment of Patients with Multiple Myeloma Who Are Not Candidates for High Dose Chemotherapy: Toxicity Comparison of Two Dose Schedules

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4047-4047 ◽  
Author(s):  
Jesus G. Berdeja ◽  
Michael R. Savona ◽  
James Essell ◽  
Patrick Murphy ◽  
Luis Chu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Herpes Zoster ◽  
Research Funding ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Off Label Use ◽  
First Line ◽  
Off Label ◽  
Grade 3

Abstract Abstract 4047 Background: Despite significant advances, multiple myeloma is an incurable plasma cell disorder with an eventual fatal outcome. In newly diagnosed MM, combinations of bortezomib, steroids and alkylating agents, such as melphalan and prednisone, have achieved response rates in excess of 70% and have been established as a standard of care in patients (pts) who are ineligible for high dose chemotherapy. Bendamustine is a bi-functional alkylating agent with a purine-like benzimidazole ring effective as a single agent and in various combinations for the treatment of relapsed/refractory MM (Poenisch et al, 2007, Fenk et al, 2007). In this study, the combination of bendamustine, bortezomib and dexamethasone (BBD) was evaluated as a first-line therapy for patients with MM. Methods: Patients with newly diagnosed active multiple myeloma who were not candidates for high-dose chemotherapy and met standard eligibility criteria with regards to renal, hepatic and hematologic function were enrolled. The original treatment schema (schema A) consisted of: bendamustine 80 mg/m2 IV on days 1, 4; bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11; and dexamethasone 40 mg on days 1, 2, 3, 4 with cycles repeating every 28 days. Patients had the option to continue on maintenance bortezomib. An interim analysis found this combination to be efficacious but relatively toxic. As a result the treatment schema was amended to the following (schema B): bendamustine 80 mg/m2 IV on days 1, 2; bortezomib 1.3 mg/m2 IV on days 1, 8, 15; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16 every 28 days for a total of 8 cycles or 2 cycles beyond documented CR, whichever occurred first. Again, patients had the option to continue maintenance bortezamib. Acyclovir or equivalent viral prophylaxis was recommended on schema A and became required on schema B. Responses were assessed using the IMWG criteria. AEs were assessed using the CTCAE Version 4.0. We report the results of an interim safety assessment of the amended BBD combination and compare the results to those seen with the original regimen. Results: Treatment schema A accrued 18 patients between 5/2010 and 2/2011. Ten patients were accrued from 10/2011 and 4/2012 and treated on treatment schema B. The median ages of treatment schemas A and B were 75 and 72.5 respectively, with all other characteristics within expected distributions and no major differences between the groups. No grades 4 hematologic Adverse Events (AEs) were seen. Grade 3 hematologic AEs were similar in both arms seen in 33% of patients on treatment schema A and 40% of patients on treatment schema B. Grade 3/4 non-hematologic AEs were seen in 72% of patients on treatment schema A and 60% of patients on treatment schema B. Although the preliminary Serious Adverse Events (SAEs) were similar with 39% of patients on treatment schema A compared to 30% of patients on treatment schema B, a large proportion of patients on treatment schema A (39%) were unable to complete the study due to toxicity or related issues. The incidence and severity of neuropathy and herpes zoster infections were significantly different between the two schemas. Schema A had 72% of patients with any grade neuropathy, with 56% being grade 2 or worse while schema B had 40% of the patients with any grade neuropathy, all but one grade 1. Likewise, 44% of patients on the original treatment reported herpes zoster while there were no cases of herpes zoster reported for patients on the revised treatment schema. Thus far, the early response rates appear similar. Schema A had an ORR of 78% (56% >vgPR) while schema B had an ORR of 90% (40% >vgPR). Conclusions: The combination of bendamustine, bortezomib and dexamethasone is feasible and efficacious in an elderly patient population. Using the revised schema, we were able to lower treatment toxicity without adversely impacting initial efficacy. Updated results will be presented at the meeting. Disclosures: Off Label Use: Off-label use of Bendamustine in the treatment of Multiple Myeloma. Chu:Millennium: Research Funding; Cephalon: Research Funding.

Prevalence of Oligoclonal Bands in Multiple Myeloma Patients Who Achieved Better Results Than Very Good Partial Response after Treatment with Standard or High Doses Chemotherapy-Final Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4210-4210
Author(s):  
Luiza soares Vieira ◽  
Edvan de queiroz Crusoe ◽  
Manuella de S. Sampaio Almeida ◽  
Lais Sousa ◽  
ana Lucia Perez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Oligoclonal Bands ◽  
High Dose ◽  
Good Partial Response

Abstract Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Collection of Peripheral Blood Stem Cells in 118 Small Children Weighing 20 Kg or less: Experience of a Single Centre

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3378-3378
Author(s):  
Jianyun Wen ◽  
Yuelin He ◽  
Libai Chen ◽  
Jing Du ◽  
Zhiyong Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Median Number ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Small Children ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Background: Peripheral blood stem cells (PBSC) are increasingly used as a source of stem cells for either autologous or allogeneic hematopoietic transplantation in children.Although technically similar to adult procedures, PBSC harvest may be difficult in young children, especially in the very small children. Aim: In this study, we aimed to evaluatethe safety and efficacy of harvesting peripheral blood hematopoietic stem cells in very small children,and to provide a guideline. Methods: Between Jan 2013 to Mar 2016, we evaluated 118 children weighing 20 kg or less, with the smallest patient weighing 11 kg. The patients had a median age of 59 months and included 72 children with thalassemia major and 46 young donors. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 10 mg/kg/day administered subcutaneously once a day and receiving oral calcium for five days before harvesting. Blood was withdrawn at a mean rate of 30-40 ml/min through a temporaryfemoral vein catheter (12 or 14 guage) to ensure adequate blood flow and returned through a larger catheter in a peripheral vein.Total nucleated cells(TNC) and CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. Results: We collected sufficient products from all the children with one to three apheresis procedures. No serious complication was detected in all children and all aphereses were completed within 4 hours.The volume of blood per kilogram processed for each apheresis ranged from 55 to 160ml (median, 85ml). The median number of TNC and CD34+ cells collected were 12×108/kg and 15×106/kg per apheresis, respectively. Conclusions:We conclude that collection of PBSC is a safe and practical procedure in children, even in very small children. Disclosures No relevant conflicts of interest to declare.

Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2234-2239 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Giovanni Martinelli ◽  
Elena Zamagni ◽  
Maria Rosa Motta ◽  
Simonetta Rizzi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Reconstitution ◽  
Cd34 Cells ◽  
Preparative Regimen ◽  
Total Body ◽  
High Dose Melphalan

Eighty-two patients with advanced multiple myeloma (MM) were enrolled in 2 sequential clinical studies of 1 or 2 courses of myeloablative therapy with stem cell support. Conditioning regimens consisted of high-dose melphalan (MEL) with or without total body irradiation (TX1 = 35) and MEL as the first preparative regimen, followed within 6 months by busulfan and melphalan (TX2 = 47). On the basis of adequate stem cell harvest, 31 patients (TX1 = 13; TX2 = 18) were transplanted with highly purified CD34+ cells. Positively selected stem cells did not adversely affect hematopoietic reconstitution compared with unmanipulated peripheral blood stem cell. Overall, the complete remission (CR) rate of evaluative patients was 13.8% and 41% for single and double autotransplant, respectively (P = .04). Moreover, 3 patients undergoing TX2 achieved molecular remission and 2 remain PCR-negative after 36 and 24 months from autograft. The median event-free survival (EFS) durations for TX1 and TX2 were 17 and 35 months, respectively (P = .03). Actuarial 3-year overall survival for patients treated with 1 or 2 transplants are 76% and 92%, respectively (P = NS). On multivariate analysis, superior EFS was associated with low β2 microglobulin (β2-M) level at diagnosis and TX2, whereas overall survival was correlated with β2-M. Positive selection of CD34+ cells did not influence the achievement of clinical or molecular CR, as well as remission duration or survival of MM patients. Thus, whereas multiple cycles of high-dose therapy may be beneficial for patients with myeloma, the clinical impact of tumor cell purging remains highly questionable.

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