scholarly journals Symptom Burden of Busulfan and Melphalan Versus Melphalan Alone for Multiple Myeloma

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 681-681
Author(s):  
Loretta A. Williams ◽  
Muzaffar H. Qazilbash ◽  
Qiuling Shi ◽  
Qaiser Bashir ◽  
Huei K. Lin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Muscle Weakness ◽  
Symptom Severity ◽  
Conditioning Regimen ◽  
Symptom Burden ◽  
Phase Iii ◽  
Dry Mouth ◽  
Fixed Dose ◽  
High Dose ◽  
Hematopoietic Stem

Abstract Background: High-dose melphalan 200 mg/m2 (Mel) is the standard for autologous hematopoietic stem cell transplantation (autoHSCT) for multiple myeloma. Retrospective analyses suggested that a combination of busulfan and melphalan (Bu-Mel) may be associated with a longer progression-free survival (PFS). A secondary aim of a randomized, phase III trial that compared the safety and efficacy of Bu-Mel vs Mel was to compare the symptom burden of the two regimens. Symptom burden is the combined impact of disease- and therapy-related symptoms on patient functional ability. Methods: Patients were randomized to Bu-Mel (Bu 130 mg/m2 daily for 4 days, either as a fixed dose or to target an average daily area under the curve of 5000 μmol-min, followed by 2 daily doses of Mel 70 mg/m)2or Mel (Mel 100 mg/m2 daily for 2 days). A subset of patients completed the 20 symptom severity and 6 interference items of MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM) prior to the start of the treatment regimen and weekly for 4 weeks post autoHSCT. Symptoms and interference are rated on 0-10 scales (0 = none or no interference, 10 = worst imaginable or complete interference). Differences in individual symptom severity and interference between the two arms were assessed by t-tests and mixed modeling. Results: As previously reported, 204 (Bu-Mel: 104, Mel: 100) were enrolled between October 2011 and March 2017. At last evaluation, 52 (51%) and 49 (49%) patients achieved a CR (p=0.88), and 69 (68%) and 67 (67%) patients achieved a CR+nCR (p=0.88) in Bu-Mel and Mel arms, respectively. Median PFS was 64.7 months and 34.4 months (p=0.013) in Bu-Mel and Mel arms, respectively. There was no difference in OS between the two arms. One hundred sixty-five of the patients (Bu-Mel: 81, Mel: 84) completed at least one MDASI-MM assessment. Median ages at autoHSCT were 57.2 and 57.0 years in Bu-Mel and Mel groups, respectively (p=0.86). At baseline, t-tests showed significantly higher mean severity of constipation (1.80, standard deviation [SD] = 2.87 vs 0.98, SD = 1.94; p=0.036), muscle weakness (2.38, SD=2.49 vs 1.44, SD=1.87; p=0.034), diarrhea (1.45, SD=2.43 vs 0.60, SD=1.10; p=0.005), and global symptom interference (2.96, SD=2.81 vs 1.77, SD=2.00; p=0.003) in the Bu-Mel arm than the Mel arm. The Bu-Mel patients had a significantly higher mean severity of pain (5.67, SD=2.65 vs 3.17, SD=3.07; p=0.0043) and mouth sores (7.35, SD=2.41 vs 1.25, SD=2.22; p <0.0001) than the Mel patients 7 days post autoHSCT. Longitudinal analysis using mixed modeling showed that the Bu-Mel arm had a significantly higher mean severity of pain (ED = 1.102, p=0.003), drowsiness (ED = 0.674, p=0.040), dry mouth (ED = 0.904, p=0.009), constipation (ED = 0.695, p=0.006), muscle weakness (ED = 0.815, p=0.006), mouth sores (ED = 1.683, p <0.0001), rash (ED = 0.362, p=0.019), and interference with physical functions (general activity: ED = 1.015, p=0.010; working: ED=1.229, p=0.006; walking: ED=0.920, p=0.009) than the Mel arm during the 4 weeks following autoHSCT. Conclusions: Patients receiving Bu-Mel vs Mel prior to autoHSCT report some differences in symptom severity, with Bu-Mel patients experiencing more severe sore mouth, pain, and symptom interference with daily functioning. The greater intensity of the double-alkylating agent conditioning regimen of Bu-Mel likely led to these differences. The increased severity of drowsiness, dry mouth, constipation, and muscle weakness may be due to an increased need for opioids to control severe pain and mouth sores. The effect of significant differences in symptom severity and interference at baseline between these two groups, despite randomization, is not clear. However, the longer time to progression of myeloma with the Bu-Mel regimen may offset the greater symptom burden early post autoHSCT. Systematic measurement of symptom burden during clinical trials can provide useful information for clinicians and patients in evaluating the full impact of different treatment regimens and enhance treatment decision making and discussion between clinicians and patients. Disclosures No relevant conflicts of interest to declare.

Comparison of conditioning regimen toxicities among autologous stem cell transplantation eligible multiple myeloma patients: High-dose melphalan versus high-dose melphalan and bortezomib

2017 ◽  
Vol 24 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Eda Aypar ◽  
Fikret Vehbi İzzettin ◽  
Şahika Zeynep Akı ◽  
Mesut Sancar ◽  
Zeynep Arzu Yeğin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Standard Of Care ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Duration Of Hospitalization ◽  
High Dose Melphalan

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.

Long-Term Follow-Up of a Randomized Phase III Multicenter Study Comparing a Standard Versus an Intensified Conditioning Regimen for High-Dose Chemotherapy in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 945-945
Author(s):  
Roland Fenk ◽  
Peter Schneider ◽  
Martin Kropff ◽  
Ali-Nuri Huenerlituerkoglu ◽  
Ulrich Steidl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
High Dose ◽  
Significant Difference

Abstract High-dose chemotherapy (HDT) improves the outcome of patients with multiple myeloma (MM) in comparison to conventional chemotherapy. Dose-escalating strategies including tandem HDT are currently evaluated to further improve remission rates and survival of patients. Therefore we conducted a randomized multicenter trial to compare an intensified conditioning regimen with the current standard high-dose melphalan. The primary study endpoint was response rate, with overall survival (OS), event-free survival (EFS) and toxicity analysed as secondary endpoints. Between 1997 and 1999 a total of 56 patients with stage II and III disease, who were matched for age (median 56 years), number of previous therapies (median time from diagnosis to transplant 7 months) and different risk factors (beta2-microglobulin, LDH, CRP, cytogentic abnormalities, chemoresistant disease, IgA-subtype, renal impairment), were randomized. All patients received 2 courses of oral idarubicine/dexamethasone and 2 courses of intravenous cyclophosphamide/adriamycine in combination with G-CSF followed by peripheral stem cell collection. Thirty patients were treated with melphalan 200mg/m2 (HD-M) whereas 26 patients received idarubicine 42mg/m2, melphalan 200mg/m2 and cyclophosphamide 120mg/kg (HD-IMC) followed by autologous blood stem cell transplantation. Acute toxicity was higher with HD-IMC, including 5 (20%) treatment-related deaths due to infections versus none (0%) in the HD-M group. This lead to early termination of the study. Severity of mucositis (grade III-IV 19 vs. 8 pts., p=0.001), CRP (20 vs. 7 mg/dl, p<0.001), days of fever (11 vs. 3, p<0.001), days with iv-antibiotics (13 vs. 4, p<0.001), number of erythrocyte-transfusions (6 vs. 2, p<0.001), number of platelet-transfusions (16 vs. 4, p<0.001) and days to granulocyte engraftment (18 vs. 11, p=0.007) were significantly higher after HD-IMC. After a follow-up of 5 years analysis restricted to patients surviving the first 30 days after HDT showed a trend to higher response rates (CR+vgPR: 47% (95%CI 24–72%) vs. 35% (95%CI 18–56%), PR 37% (95%CI 17–63%) vs. 48% (95%CI 29–68%) and time-to-progression (median 31 vs. 15 months, p=0.1) in the HD-IMC treatment arm in comparison to HD-M, but there was no significant difference in EFS and OS (median 22 vs. 30, p= 0.31 and 66 vs. 66 months, p=0.8, respectively). Univariate analysis demonstrated that LDH levels > 200 U/L (p=0.04) and chemoresistant disease (p=0.05) were a bad prognostic factor for EFS. Beta2-Microglobulin levels > 5mg/dl (p=0.01), abnormal conventional cytogenetics (p=0.02) and LDH levels > 200 U/L (p=0.03) were predictive for an inferior OS. In conclusion intensified conditioning for HDT had an intolerable high treatment-related mortality and did not improve EFS and OS in patients with multiple myeloma.

Preliminary Evidences of Circulating Inflammatory Markers Associated with Symptom Development In Patients with Multiple Myeloma During Induction Therapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4734-4734
Author(s):  
Xin Shelley Wang ◽  
James M Reuben ◽  
Bang-Ning Lee ◽  
Robert Z. Orlowski ◽  
Valen E Johnson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Period ◽  
Inflammatory Cytokines ◽  
Muscle Weakness ◽  
Induction Therapy ◽  
Symptom Severity ◽  
Symptom Burden ◽  
Cytokine Receptors ◽  
Symptom Development ◽  
The Relationship

Abstract Abstract 4734 Background: Disease progression in multiple myeloma (MM) is highly related to cytokines, particularly interleukin (IL)-6, which promotes the growth of MM and is essential for the proliferation of malignant plasma cells. However, there are few reports delineating the relationship between levels of circulating cytokines and the severity of symptoms that patients experience during induction therapy. Methods: Thirty-four patients with MM were enrolled in this ongoing study before or within 2 cycles of induction therapy (with majority of bortezomib based and few thalidomide based). Multiple symptoms were measured by M. D. Anderson Symptom Inventory – MM module (MDASI-MM) twice a week during induction therapy. Sera were collected at baseline and during every cycle of induction therapy to measure cytokines by Luminex Multiplex Bead Array assay. Using ordinal regression models, we examined the hypothesis that concentration of serum inflammatory cytokines would be associated with symptom burden in patients with MM during induction therapy, especially therapy induced symptoms. The modeling was adjusted for time from induction therapy, age, sex, staging, Eastern Cooperative Oncology Group performance status (PS), opioid use, and body mass index (BMI). Symptom severity ratings were treated as ordinal responses. A log scale of cytokine concentrations was used for modeling. Results: From longitudinal symptom profile modeling, in general, female patients and patients with poor PS (PS ≥ 2) reported significantly higher level of symptoms than male patients and those with good PS. Overall, the most severe symptoms included fatigue, muscle weakness, sleep disturbance, pain, drowsiness, numbness and bone aches during the induction period. Several sickness symptoms show a trend, although not statistically significant, of decrease during the first cycle of induction therapy. By the end of the first cycle of induction therapy, we observed significant increases in therapy induced symptoms which included numbness, muscle weakness, difficulty remembering, poor attention and diarrhea (all P<0.05). Thereafter, symptoms stabilized or increased in severity for the remainder of induction period (see figure 1 Lowess curves for selected symptoms items on MDASI). Among the panel of inflammatory cytokines and soluble cytokine receptors (sIL-6R and sTNF-R1), monocyte chemoattractant protein, and C-reactive proteindemonstrated statistically significant relationships with severity of the majority of symptoms over time of induction therapy. Because of the non linear trajectory of symptom development, we tested the relationship between symptoms and cytokines by therapy cycle. There were no statistically significant correlations between any symptoms and cytokines (IL-6, IL-8, IL-10, and interferon-gamma, IL-1 receptor antagonist, soluble receptors, and angiogenic factor, vascular endothelial growth factor. On the other hand, sIL-2R, IL-2, and TNF-a were significantly correlated with few symptoms. Conclusion: Soluble cytokine receptors can play an important role in the development of MM and treatment-related symptoms. Hierarchical dynamic modeling can be used to assess the statistical relationship between biomarkers and the severity of symptoms. With a larger sample, the symptom and cytokine profile by patient's tumor response will be analyzed to address the interaction between cytokines and disease as well as therapy-driven symptom burden. The results of these studies that yield empirical information on expected symptom burden could be very useful for the management of symptoms and improved clinical management of patients. Figure 1. Symptom severity profile during induction therapy in MM patients Disclosures: No relevant conflicts of interest to declare.

Cyclophosphamide Mobilization Does Not Improve Outcome in Patients Transplanted for Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1165-1165
Author(s):  
David Dingli ◽  
Grzegorz S. Nowakowski ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Cell Labeling ◽  
High Dose ◽  
Significant Activity ◽  
Time To Progression ◽  
Hematopoietic Stem ◽  
Myeloma Cells ◽  
The Impact

Abstract Patients with multiple myeloma (MM) who undergo high dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) and achieve a complete response (CR) have a superior overall survival (OS) and time to progression (TTP). Thus achieving a CR is an important goal of therapy with ASCT. Cyclophosphamide has significant activity against MM and is often used in high doses prior to ASCT for mobilization of hematopoietic stem cells. We hypothesized that high dose cyclophosphamide (HDC) may further improve CR rates in patients undergoing ASCT. Methods: The Mayo Clinic myeloma transplant database was searched for patients without circulating myeloma cells who had stem cell mobilization with hematopoietic growth factor (HGF) alone or HDC followed by HGF. Relevant demographic, clinical and laboratory characteristics were abstracted. The main outcome studied was the impact of HDC on CR rates and time to progression (TTP) to myeloma. Results: We identified 201 patients without circulating myeloma cells. Of these, 127 were mobilized with HDC and HGF and 74 with HGF alone. The two cohorts were similar with respect to age, gender, isotype, B2M, plasma cell labeling index, cytogenetics, conditioning regimen, disease status at time of transplant with no statistically significant differences between the two cohorts. CR rates were 37.4 and 41.3% (p=0.6115) for patients mobilized with HDC/HGF and HGF respectively. TTP was 19.9 and 17.6 months (p=0.6039) respectively. The median number of collection sessions for patients mobilized with HDC/HGF was 2 (1–10) and those mobilized with HGF was 4 (1–10) (p&lt;0.0001). In a multivariate analysis for TTP, cytogenetics and achieving a CR were the only independent variables (p=0.0012 and p&lt;0.0001). Conclusion: HDC for autologous hematopoietic stem cell collection reduces the number of collections necessary to support HDT/ASCT. However, HDC does not increase CR rates or improve on TTP for patients undergoing ASCT.

A Phase 2 Study of Bendamustine Plus Melphalan Conditioning for Second Autologous Stem Cell Transplantation in "De-Novo" Multiple Myeloma Patients in a Tandem Transplant Strategy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3197-3197
Author(s):  
Massimo Martino ◽  
Messina Giuseppe ◽  
Roberta Fedele ◽  
Giuseppe Irrera ◽  
Console Giuseppe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
De Novo ◽  
Conditioning Regimen ◽  
Phase Iii ◽  
High Dose

Abstract Background: High-dose melphalan (HDM) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Bendamustine (BENDA) has a proved activity in hematological malignancies including both first line and relapsed MM. Methods: We conducted a phase II trial, adding BENDA to HDM before second ASCT, in a tandem ASCT strategy, in 32 patients with "de-novo" MM. All patients received a bortezomib-based induction therapy. High-dose cyclophosphamide (CY) and G-CSF were used to mobilize stem cells. Four to 6 weeks after the administration of CY, patients received HDM (200 mg/mq), followed by ASCT. Three to 6 months after the first transplantation, patients received a second ASCT with BENDA (200 mg/m2) to HDM (140 mg/m2) as conditioning regimen (BM). Results: The median age was 56 years (range 40 to 66). Overall, there was no transplant related mortality. The incidence of neutropenic fever and mucositis (grade 1-2) was 46.9% and 81.2%, respectively. No mucositis grade 3-4 was observed. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response (CR) improved to 62.5%. Overall response rate was 90.6%. After a median follow-up of 18,2 months, 4 patients had progressed and 1 died. Median progression free survival (PFS) was not reached and actuarial 2-year PFS and OS was 78% and 90%, respectively. Conclusion: Bendamustine plus melphalan is feasible as conditioning regimen for second ASCT in MM and should be explored for efficacy in a phase III study. Longer follow-up is needed to evaluate conversion rate and survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals Symptom Burden of Busulfan + Melphalan Versus Melphalan Alone for Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1277-1277 ◽  
Author(s):  
Loretta A. Williams ◽  
Muzaffar H. Qazilbash ◽  
Qiuling Shi ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Symptom Severity ◽  
Symptom Burden ◽  
Hematopoietic Stem ◽  
Disturbed Sleep

Abstract Background: High-dose melphalan at 200 mg/m2 (Mel) is the standard for autologous hematopoietic stem cell transplantation (autoHSCT) for multiple myeloma. Two recent retrospective analyses suggested that a combination of busulfan and melphalan (Bu-Mel) may be associated with a longer progression-free survival (PFS). A secondary aim of a randomized phase III trial that compared the safety and efficacy of Bu-Mel vs Mel was to compare the symptom severity and symptom burden of the two regimens. Symptom burden is defined as the combined impact of disease- and therapy-related symptoms on patient functional ability. Methods: Patients were randomized to Bu-Mel or Mel. In the Bu-Mel arm, Bu 130 mg/m2 was infused daily for 4 days, either as a fixed dose or to target an average daily area under the curve (AUC) of 5000 μmol-min, followed by 2 daily doses of Mel at 70 mg/m2. A subset of patients completed the 20 symptom severity and 6 interference items of MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM) prior to the start of the treatment regimen and weekly for 5 weeks post autoHSCT. Symptoms and interference are rated on 0-10 scales (0 = none or no interference, 10 = worst imaginable or complete interference). Differences in individual symptom severity and interference and symptom burden (the composite mean scores of the 5 most severe symptoms and the 6 interference items) between the two arms were assessed by t-tests and mixed modeling at each time point. Results: As previously reported, 92 patients (Bu-Mel: 49, Mel: 43) were enrolled between October 2011 and August 2013. Grade 3-4 non-hematologic toxicity was seen in 41 (84%) and 20 (47%) patients in Bu-Mel and Mel, respectively (p=0.0003). At day 90, 8 (18%) and 15 (35%) patients had achieved a CR (p=0.05), and 13 (27%) and 20 (47%) patients had achieved a CR + nCR (p=0.05) in Bu-Mel and Mel, respectively. One-year PFS was 93% and 82% (p=0.26), and 1-year OS was 100% and 100% in Bu-Mel and Mel arms, respectively. Fifty-six of the patients (Bu-Mel: 29, Mel: 27) completed at least one MDASI-MM assessment between October 2011 and July 2013. Median ages at autoHSCT were 55.5 and 55.1 years in Bu-Mel and Mel groups, respectively (p=0.862). At baseline, t-tests showed significantly higher mean severity for bone aches (3.00, standard deviation [SD] = 2.85 vs 1.40, SD = 1.94; p=0.022), drowsiness (2.96, SD = 3.12 vs 1.44, SD = 1.87; p=0.034), muscle weakness (2.98, SD = 2.68 vs 0.79, SD = 1.14; p=0.001, appetite (1.93, SD = 2.60 vs 0.44, SD = 1.19; p=0.009), and overall interference (3.46, SD = 2.89 vs 1.03, SD = 1.04; p<0.001) in the Bu-Mel arm than the Mel arm. Longitudinal analysis using mixed modeling showed a significant difference in the combined mean of the 5 most severe symptoms (fatigue, pain, drowsiness, disturbed sleep, and lack of appetite) at baseline (estimated difference [ED] = 1.16, p=0.016) between the arms and a significant increase in the top 5 symptoms for both arms between baseline and Weeks 1 (ED = 3.30, p<0.0001), 2 (ED = 2.06, p=0.002), and 3 (ED = 2.28, p=0.003). The Bu-Mel arm had a significantly lower mean severity of disturbed sleep at Week 4 (ED = -3.69, p=0.022) and significantly lower mean severity of lack of appetite at Week 2 (ED = -3.08, p=0.016) and 3 (ED = –3.15, p=0.033) than the Mel arm, but a significantly higher mean severity of sore mouth at Week 1 (ED = 2.35, p=0.018) and 2 (ED = 2.51, p=0.009). Conclusions: Patients with MM undergoing autoHSCT report a significant increase in symptom severity and interference during Weeks 1 to 3 post autoHSCT, with the greatest increase occurring during the first week. In addition, patients receiving Bu-Mel vs Mel report differences in individual symptom severity, with Mel patients having significantly more problems with disturbed sleep and lack of appetite and Bu-Mel patients reporting significantly more severe sore mouth and throat. The effect of the significant differences prior to the start of autoHSCT between these two groups, despite randomization, in the severity of the top 5 symptoms and interference on symptom report during autoHSCT is unclear and will be further explored. Additional differences in symptom severity may have gone undetected in this study because of initial differences. Systematic measurement of symptom burden during clinical trials can provide useful information for clinicians and patients in evaluating the full impact of different treatment regimens. Disclosures Off Label Use: Busulfan and melphalan for conditioning regimen prior to autologous hematopoietic stem cell transplantation for multiple myeloma. Qazilbash:Otsuka Pharmaceutical Company: Research Funding.

scholarly journals Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Statistical Significance ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cell Engraftment ◽  
The Difference ◽  
High Dose Melphalan

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2684-2691 ◽  
Author(s):  
Sergio Giralt ◽  
William Bensinger ◽  
Mark Goodman ◽  
Donald Podoloff ◽  
Janet Eary ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Phase 1 ◽  
High Dose ◽  
Two Phase ◽  
Hematopoietic Stem

Abstract Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation. (Blood. 2003;102:2684-2691)

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