Peripheral Blood Stem Cell (PBSC) Harvest Is More Expensive Following Bortezomib-Based Therapy in Multiple Myeloma (MM), Related to Increase Number of Days of Collect.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1373-1373
Author(s):  
Matthieu Barthelemy ◽  
Florence Boulanger ◽  
Houria Debarri ◽  
Laurent Pascal ◽  
Pierre Samarcq ◽  
...  

Abstract Abstract 1373 Poster Board I-395 Background: High-dose therapy is the front line treatment of reference in young patients with Multiple Myeloma (MM). Although induction therapy remains a matter of controversy, bortezomib-based therapy is considered more and more as a standard of care. Prior to autologous stem cell transplantation (ASCT), patients undergo PBSC collect, usually starting after cycle 2 to 4 of the induction treatment. Currently, patients receive one transplant at front line, but most of the patients will benefit throughout the MM disease history of a second or a third ASCT procedure. We have noticed that the number of days of collection vary from patient-to-patient following bortezomib-based induction therapy. This increase in collection procedures might increase the cost of PBSC harvest with more patients discomfort and staff unavailability. We have therefore further studied the quality, yields and days of collection in myeloma patients following bortezomib-based therapy as compared to other regimens-based treatment courses. Material and Method: We retrospectively studied 70 patients with myeloma that underwent PBSC harvestsafter mobilization with GCSF following debulking with bortezomib-based therapy (58 days of procedures – 26 patients) versus other agents-based therapy [65 days of procedure – 44 patients; VAD vincristine, adriamycin, dexamethasone). Results: -Yields. CD34 Mobilization is lower following bortezomib-based therapy as compared to other regimen-based therapy. Similarly, more days of collection are also needed to collect the requested yield of PBSC. -Engrafment. No significant differences regarding engraftment was noticed among the 2 groups studied. The days to neutrophil and platelet counts recovery, the number of days with fever and the number of red cell and platelet transfusions were not significantly different between the 2 groups, mobilization following bortezomib-based therapy versus other regimen-based therapy, respectively. Conclusion: In our series, bortezomib-based induction regimen does not increase the number of PBSC harvest failure and the quality of engraftment was identical to other regimen-based induction treatment. However, CD34 mobilization was lower following bortezomib-based therapy, which explains lower daily harvest counts and therefore an increase number of days of collection in bortezomib-based treated patients. Therefore, PBSC harvest procedure following bortezomib-based therapy significantly increases the cost of PBSC collection. These results need to be confirmed in larger studies. New agents in use for mobilization might be considered for future PBSC collection in bortezomib-based treated patients. Disclosures: Leleu: Janssen Cilag: Research Funding.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2926-2926 ◽  
Author(s):  
Geoffrey L. Uy ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Michael H. Tomasson ◽  
John F. DiPersio ◽  
...  

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the proteasome approved for the treatment of relapsed or refractory multiple myeloma (MM). Emerging evidence indicates that bortezomib is also effective alone or in combination with cytotoxic agents in the front-line treatment of myeloma. Given the superiority of high dose therapy with autologous transplant compared to conventional therapy in myeloma, the application of bortezomib to novel front-line therapies depends in part on its effects on subsequent stem cell mobilization and engraftment. Previous reports have demonstrated successful chemotherapy induced mobilization of stem cells following bortezomib. To determine the effects of bortezomib on cytokine mobilization and engraftment of stem cells, we conducted a study of bortezomib administered prior to high-dose melphalan with autologous stem cell transplant. Following induction therapy, 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 cells were mobilized with G-CSF 10 mcg/kg/day for 5 days and harvested by large volume apheresis (20 L/day) until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Melphalan 100 mg/m2/day x 2 days was administered followed by reinfusion of peripheral blood stem cells 48 hours later. GM-CSF 250 mcg/m2/day was given post-transplant until the ANC ≥ 1,500/mm3 for 2 consecutive days. Forty patients were enrolled in this study with 37 continuing on to autologous transplant. Study population consists of 24 male and 16 female patients with the median age at enrollment of 56 years (range 38–69). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (29), IgA (10), light chain only (1), with stage I (1), II (12), or stage III (27) disease. Prior to receiving bortezomib, 20 patients had been previously treated with an anthracycline containing regimen and 22 with thalidomide for induction therapy. Two patients did not receive any prior chemotherapy. Two patients did not proceed to stem cell harvest, one secondary to disease progression on bortezomib and the other because of a stroke suffered during G-CSF mobilization. Stem cell collection was successful in 37 of 38 patients with the first collection containing a median of 4.24 x 106 CD34+ cells/kg. The majority of patients (29) required a single pheresis session, 7 required two sessions, and 1 patient required 5 sessions. The only patient failing stem cell collection had received extensive radiation to the pelvis in addition to a prior history of breast cancer for which she received adjuvant chemotherapy. All transplanted patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 11 days (range 9–31 days). In an intention-to-treat analysis at 100 days post-transplant, we observed a compete response (CR) in 6 patients (15%), a near CR in 10 patients (25%) with an additional 19 partial responses (48%) for an overall response rate of 88%. We conclude that pre-transplant treatment with 2 cycles of bortezomib following anthracycline or thalidomide containing chemotherapy does not adversely affect stem cell yield or time to engraftment and results in high CR / near CR rates.


2017 ◽  
Vol 24 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Eda Aypar ◽  
Fikret Vehbi İzzettin ◽  
Şahika Zeynep Akı ◽  
Mesut Sancar ◽  
Zeynep Arzu Yeğin ◽  
...  

Background Autologous hematopoietic stem cell transplantation (AHSCT) remains the standard of care for younger patients with multiple myeloma (MM). Currently, high-dose melphalan (HDM) is recommended as conditioning regimen before AHSCT. Preclinical data suggest that combining bortezomib and melphalan has synergistic effect against multiple myeloma cells. Bortezomib and HDM (Bor-HDM) combination as conditioning regimen has been investigated by many other investigators. Objective In this retrospective study, we aimed to compare transplant-related toxicities and hematologic recovery of HDM and Bor-HDM conditioning regimens. Method We retrospectively evaluated hematologic recovery and toxicity profile in patients with MM who received AHSCT with either HDM ( n = 114) or Bor-HDM ( n = 53) conditioning regimen. Results Nonhematologic toxicities were comparable between HDM and Bor-HDM conditioning regimen, except mucositis and diarrhea being more frequent in the Bor-HDM group. Neutrophil and platelet engraftment time and duration of hospital stay were significantly shorter for HDM regimen. Conclusions In this retrospective analysis, we observed engraftment kinetics and duration of hospitalization were significantly worse in Bor-HDM conditioning regimen with manageable toxicities. Randomized studies are needed to further compare Bor- HDM regimen to HDM in terms of response rates, toxicities, and transplant-related mortality.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5117-5117 ◽  
Author(s):  
Patrizia Tosi ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Giulia Perrone ◽  
Michela Ceccolini ◽  
...  

Abstract Bone disease occurs in approximately 80% of patients with newly diagnosed multiple myeloma (MM) and is caused by the interaction of the neoplastic clone with bone marrow microenvironment, ultimately resulting in an altered balance between bone resorption and bone formation. It has been previously reported that therapies aimed at eradicating the myeloma clone could contribute to decrease bone resorption, even though bone formation remains impaired even in responding patients, due to the use of high-dose steroids. It has been recently demonstrated, both in vitro and in animal models, that Bortezomib improves bone formation by stimulating osteoblasts. In order to test whether this activity was retained also in vivo, we evaluated markers of bone resorption (serum crosslaps) and bone formation (serum osteocalcin-OC and bone alkaline phosphatase - BAP) in a series of patients who were enrolled in the “Bologna 2005” phase III clinical trial at our Center. By study design, after registration patients were randomized to receive three 21-days courses of induction therapy with either VTD (Bortezomib, 1.3 mg/sqm on d 1, 4, 8, and 11, plus Dexamethasone, 40 mg on each day of and after Bortezomib administration plus Thalidomide 200 mg/d from d 1 to 63.) or TD (Thalidomide as in VTD and Dexamethasone 40 mg/d on d 1–4 and 9–12 of every 21-d cycle), prior to stem cell collection and double autologous stem cell transplantation. As of January 2008, 27 patients (19 male and 8 female, median age = 57.5 yrs) entered the sub-study; of these, 15 and 12 patients were randomized in the VTD and TD arm, respectively. At diagnosis, both groups of patients showed a marked increase in serum crosslaps as compared to upper baseline limit (7321±1445pmol/L in the VTD arm and 11140±2576pmol/L in the TD arm) while both OC and BAP were reduced as compared to lower baseline limits. After completion of the induction therapy, serum crosslaps were significantly decreased in both treatment groups (2747±319pmol/L in VTD arm, p=0.007; 3686±1084pmol/L in the TD arm, p=0.0015). In the TD group a significant further reduction in bone formation markers was also observed (42% reduction in serum OC and 30% in BAP, p=0.03 and 0.04 as compared to pre-treatment values); on the contrary, in the VTD arm both OC and BAP were not significantly decreased as compared to baseline values (15% and 11% for OC and BAP, respectively). These data suggest that incorporation of Bortezomib into induction therapy counteracts the inhibitory effects of high-dose steroids on osteoblastogenesis, thus sparing bone formation.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3408-3408
Author(s):  
Lionel Karlin ◽  
David Ghez ◽  
Marie-Olivia Chandesris ◽  
Sylvain Choquet ◽  
Margaret Macro ◽  
...  

Abstract Abstract 3408 Poster Board III-296 The t(4;14)(p16.3;q32), leading to the ectopic expression of two potential oncogenes, the Multiple Myeloma Set Gene (MMSET) and the Fibroblast Growth Factor 3 (FGFR3), is found in 15% of patients with multiple myeloma (MM) and is associated with a very poor prognosis. We previously shown in patients under 65 years of age that High Dose Therapy followed by Peripheral Blood Stem Cell Transplantation (HDT-PBSCT) provides a high response rate (RR) but a very short median relapse-free survival of only 11 months. In addition, relapses are often aggressive and chemoresistant. Thus, more effective regimen is urgently needed. We prospectively studied 23 t(4;14) MM patients treated with 3 or 4 cycles of a combination of Bortezomib and Dexamethasone (VD) (n=4) or of Bortezomib, Adriamycine and Dexamethasone (PAD) (n=19) as induction treatment before HDT-PBSCT (Melphalan 200 mg/m2). T(4;14) was detected using real time quantitative PCR searching for IGH/MMSET and FGFR3 transcripts. RR, event-free survival (EFS) and overall survival (OS) were evaluated. Median age at diagnosis was 51 years (range, 33-64). Isotype was IgA in 12 (52%) patients. All patients had stage II or III MM. An elevated serum β2m level (>3.5 mg/L) was found in 14 (61%) patients, and a low haemoglobin (Hb) level (<10 g/dL) in 10. Four presented with renal failure and 5 with hypercalcemia. Three (16%) of 19 patients had a t(4;14) without expression of FGFR3. After induction treatment with VD or PAD, PBSC were successfully harvested with granulocyte-colony stimulating factor only (n=15) or following a cycle of high-dose cyclophosphamide (n= 7). RR after induction treatment was complete response (CR) in 6 (26%) patients, very good partial response (VGPR) in 9 (39%), partial response (PR) in 3. Five patients had refractory or progressive disease (PD), including 1 who died before stem cell mobilization. RR after HDT was CR in 11 (48%), VGPR in 4 (17%) and PR in 4 (overall RR of 82%). Three had PD. With a median follow-up of 18 months (range, 3-32), 9 (39%) patients are alive without relapse, including 4 with a 19, 27, 30 and 32 months follow-up respectively. Twelve (52%) patients relapsed. Two patients died in the first month post HDT from PD. We found a median EFS and OS from initiation of therapy of 14.7 and 30.9 months respectively. EFS was not influenced by Hb and/or serum β2m level. However, we found a significantly longer OS in patients with low β2m (median non reached) as compared to patients with high β2m (median=23.1 months, p=0.04). These preliminary results illustrate the heterogeneity of this disease and indicate that some t(4;14) MM patients seem to benefit from bortezomib containing regimen as induction treatment before HDT in term of EFS and OS. A larger series with a longer median time of follow up will be presented. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2044-2044
Author(s):  
Jin Seok Kim ◽  
Cheolwon Suh ◽  
June-Won Cheong ◽  
Kihyun Kim ◽  
Yang Soo Kim ◽  
...  

Abstract Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5118-5118
Author(s):  
Tareq Braik ◽  
Dayra Avila ◽  
Shivi Jain ◽  
Manila Gaddh ◽  
Barabara Yim ◽  
...  

Abstract Abstract 5118 Introduction: Since the mid 1990s, high dose chemotherapy with hematopoietic stem cell rescue has been considered the standard of care for front-line treatment in younger patients with multiple myeloma. This standard of care has been based on randomized controlled trials that compared autologus stem cell transplant (ASCT) with conventional chemotherapy. During the past decade, novel agents (NA), thalidomide, bortezomib and lenalinomide, have replaced conventional chemotherapy in the treatment of myeloma. These agents, used frontline, have shown promise in improving the outcome of myeloma patients without increasing toxicity. There are no studies to date comparing NA therapy to ASCT to determine whether there is a survival difference or whether NA therapy may reduce the need for transplantation. Many of our patients have no health insurance coverage and transplant is not a therapeutic option for them. We have attempted to compare the outcome of such patients receiving NA therapy with those in the literature who received conventional chemotherapy followed by ASCT. Methods: Ninety nine patients with multiple myeloma were treated at John H Stroger Hospital of Cook County between 2001 and 2011. All patients received novel agents (thalidomide, bortezomib and lenalinomide) as part of their therapy. Only 18/99 (18.2%) went for high-dose chemotherapy with ASCT and the remaining 81/99 (81.8%) received novel therapy without ASCT. We compared the outcome of patients who received novel therapy alone to a historical control group from the literature who received ASCT with conventional therapy (N Engl J Med 2003;348:1875–83). Overall survival was determined by Kaplan-Meier estimates. Results: We evaluated 99 consecutive myeloma patients (38% males and 61% female) of which 65% were African Americans, 19% Hispanics and 7% whites. All 3 stages (international staging system) of myeloma were equally represented. The median age at diagnosis was 60 years (40–85yr). Median follow up was 48 months (12–120). During the ten year follow up period, 60 patients (60.4%) have died. Twenty four out of 99 patients (24.2%) received only one line of therapy. 75 patients received more than one line of therapy. 75% received thalidomide-based therapy, 13% received bortezomib-based therapy and 12% received lenalinomide-based therapy. The median survival of patients who received novel therapy without ASCT (n=81) was 60 months, which is higher than the median survival of the historical controls who received ASCT reported by Child et al, N Engl J Med 2003;348:1875–83, (median survival = 54.1 months), the difference was statistically significant (P=0.0329). There was no statistically significant difference between the two groups by sex (p=0.927) and race (p=0.421). The 5-year survival of patients who received novel therapy without ASCT (n=81) was 48.2%. For those who were younger than 65 years (n=54), the median survival was 72 months and the 5-year survival was 58.1% in comparison to those who were 65 years and older (n=27), the median survival was 46 months and the 5-year survival was 29.2% (P=0.029). Conclusion: Novel agents are effective frontline therapy for multiple myeloma, especially in patients younger than 65. Our cohort had remarkable results in comparison to a historical population of patients who had ASCT with conventional chemotherapy. Since there is no curative therapy to date, a prospective randomized trial comparing NA with ASCT will be essential to clarify the role of ASCT in the era of novel therapy. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5691-5691
Author(s):  
Matevz Skerget ◽  
Matjaz Sever ◽  
Barbara Skopec

Abstract Background Multiple myeloma (MM) is a hematologic disease characterized by accumulation of malignant plasma cells in the bone marrow. Triplet induction regimens incorporating bortezomib, thalidomid and dexamethasone (VTD) or bortezomib, cyclophosphamide and dexamethasone (VCD) are current standard of care because of improved response and prolonged progression free survival (PFS) and overall survival (OS). Autologous hematopoietic stem cell transplantation (aHSCT), performed in first remission or at relapse, is standard of care for younger fit patients. Successful mobilization and collection of peripheral blood stem cells (PBSC) is required before aHSCT. A target dose of 2 x 106 PBSC per kg body weight is considered a minimum for timely hematopoetic reconstitution, although a higher dose, 3 to 5 x 106 PBSC per kg body weight, is thought to be optimal for earlier engraftment. Mobilization with chemotherapy (intermediate doses of cyclophosphamide) and granulocyte-colony stimulating factor (G-CSF) is a standard in most transplant centers and provides higher stem cell yields in fewer apheresis procedures, at the cost of increased toxicity and less predictable onset date of apheresis in comparison to G-CSF alone mobilization. G-CSF alone mobilization fails to achieve the target doses of PBSC in up to 20 % of patients. There is limited information on possible impact of novel agents on ability to successfully mobilize and harvest PBSC. From available data, the impact of thalidomide on stem cell mobilization is small and probably not of clinical significance, but most of it comes from trials incorporating mobilization with chemotherapy and not G-CSF alone mobilization. Due to feasibility and safety reasons our institution uses G-CSF alone mobilization in MM patients. Mobilization with chemotherapy and/or prelixafor is reserved for poor mobilizers. The aim of our study was to retrospectively evaluate the success of GCSF alone mobilization in patients who received either VTD or VCD induction and possible differences between two groups. Patients and methods We retrospectively analyzed data from our national registry from the 1/1/2014 until 12/31/2017. Seventy-two patients with newly diagnosed MM that received induction treatment with VTD or VCD and underwent stem cell mobilization with G-CSF alone were included. VTD treatment consisted of 3 week cycles of bortezomib 1.3 mg/m2 subcutaneous on days 1, 4, 8 and 11, thalidomide 100 mg daily and dexamethasone 40 mg on days 1 - 4 of the first cycle and once per week thereafter. VCD treatment incorporated bortezomib and dexamethasone at the same schedule as for VTD plus cyclophosphamide 500 mg/m2 on day 1, 8 and 15 of each cycle. Following 3 - 4 cycles of induction treatment, stem cells were mobilized using daily subcutaneous injections of G-CSF 10 mg/kg body weight (doses were rounded up according to available 300 mcg and 480 mcg vials) for 5 consecutive days. The number of circulating PBSC was determined in peripheral blood on day 5 by flow cytometry and apheresis was initiated at a CD34+ cell count > 20/μL. A dose of 2 × 106 PBSC per kg body weight and 3 × 106 PBSC per kg body weight were considered the minimal and optimal dose for a single transplant. Results Twenty-eight and 44 patients received induction treatment with VCD or VTD respectively (Table 1). The mobilization failure rate between the groups was 7 % and 9 % for VCD and VTD. There was no statistical difference in the number of apheresis procedures, collected PBSC and the ability to collect a minimal and optimal dose for 2 aHSCT between the two groups (Table 2). Conclusions Due to higher efficacy, VTD is preferred over VCD with no data available on the impact of these regimens on stem cell mobilization with G-CSF alone. The results of our retrospective study showed that thalidomide in the VTD regimen did not influence the number of collected PBSC or the number of apheresis procedures compared to VCD. The failure rate for both groups was low. There was no statistical difference in collecting the optimal dose for two aHSCT between the groups. In conclusion, induction with VTD can be safely used in centers using G-CSF alone mobilization without compromising the ability for stem cell harvest. Disclosures No relevant conflicts of interest to declare.


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