Bendamustine Plus Melphalan As Conditioning Regimen for Second Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: Single Centre Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2516-2516 ◽  
Author(s):  
Massimo Martino ◽  
Giuseppe Messina ◽  
Tiziana Moscato ◽  
Roberta Fedele ◽  
Giuseppe Console ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Phase 1 ◽  
Conditioning Regimen ◽  
First Line

Abstract Background: Bendamustine has a proved activity in hematological malignancies including both first line and relapsed multiple myeloma (MM). Moreover Bendamustine is generally well tolerated, with the majority of adverse events mainly limited to myelosuppression. Recently Mark et al published a phase I trial adding escalating doses of Bendamustine to the current standard conditioning of Melphalan 200 mg/m2 (HDM) in patients with MM at their first transplant. No transplant related mortality (TRM) was observed and the regimen was well tolerated. Recently was stated that double autologous stem cell transplantation (ASCT) improve the outcome of patients achieving a poor response after first ASCT. Although HDM is the standard for conditioning in MM, in some cases the CR rate is lower than expected. In this trial we evaluate feasibility and efficacy of the association of Bendamustine and Melphalan (BM) as conditioning regimen to second ASCT in patients with MM. Methods: This study was approved by local ethic committee.Between January and June 2014, 12 patients with MM underwent second ASCT following BM as conditioning regimen. The median age was of 56 years (range 40-66), 8 male and 4 female with a diagnosis of MM, stage IIIA (n=7), IIIB (n=4) and IIA (n=1). All patients received a bortezomib-containing regimen as first-line induction therapy and received Melphalan 200 mg/m2 as conditioning regimen before the first ASCT. All patients urderwent second ASCT following Bendamustine (100 mg/m2 days -4 and -3) and Melphalan (140 mg/m2 day -2) as conditioning regimen. G-CSF were given at day 5 after transplant. Results: A median number of 4.9x106/kg of CD34+ cells (range: 4-6.2) was infused. All patients engrafted, with median time to reach neutrophil>500/µl and platelet >20.000/µl of 12 days (range, 11 to 15) and 14 (range, 11 to 19), respectively. Overall, the BM regimen was well tolerated. Almost all patients experienced mucositis, nausea and diarrhea but all events were of grade 1 or 2 (grade 3 diarrhea occurred in only 1 patient). Four patients (33%) had fever (grade 1 or 2) that was clinically identified in 2 cases (pneumonia and cystitis). The median time of duration of fever was 4 days (range, 2-6). No TRM occurred after at least day + 90 after transplant. Overall, no added toxicity were observed between the first and second ASCT. At day + 90 after first and second transplant response rate was respectively: 1 CR, 10 VGPR, 1 PR and 4 CR, 5 VGPR, 1 PR, 2 too early. Three patients in VGPR after first transplant converted to CR after second ASCT. Conclusion: Bendamustine plus Melphalan is feasible as conditioning regimen for second ASCT in patients with MM. The regimen was well tolerated and the toxicity profile of ASCT with conditioning regimens BM or Melphalan is comparable. Longer follow-up is needed to evaluate conversion rate and survival. References: Mark TM et al. A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2013 May;19(5):831-7. Disclosures No relevant conflicts of interest to declare.

High-dose lenalidomide and melphalan as conditioning for autologous stem cell transplantation in relapsed or refractory multiple myeloma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8021-8021
Author(s):  
Adriana C. Rossi ◽  
Jorge Monge ◽  
Ruben Niesvizky ◽  
Jing Mei Hsu ◽  
Tsiporah Shore ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase 1 ◽  
Conditioning Regimen ◽  
High Dose ◽  
Refractory Multiple Myeloma

8021 Background: Autologous stem cell transplantation (ASCT) remains a standard of care of eligible patients with multiple myeloma, despite the many novel therapies introduced over the past decade. High dose melphalan (HDM) is the only approved regimen to date. Lenalidomide (LEN) is an oral immunomodulatory drug which has become the backbone of myeloma therapy from induction through salvage and maintenance. Early studies noted a dose response relationship, and found myelosuppression to be the dose limiting toxicity. We previously reported on our phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT, where no DLT was noted up to 350mg PO daily of LEN. Here we report the phase 2 data of patients undergoing ASCT with combination conditioning regimen. Methods: 50 patients with relapsed/refractory multiple myeloma (RRMM) underwent ASCT using HDLEN+HDM conditioning. HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. TPatients were heavily pre-treated: 32% had prior HDM-ASCT, 96% had received prior lenalidomide, and 42% prior pomalidomide; 40% prior anti-CD38 mAB. Of note, 68% entered the study with progressive disease at time of enrollment. Results: Overall response rate was 96%, with 80% being ≥VGPR. Median progression free survival (PFS) was noted at 14.3 months, while overall survival (OS) was 68.2 months. PFS was similar when patients were stratified by prior ASCT, depth of response at enrollment, or presence of high risk FISH. Toxicities were mostly hematologic (100% neutropenia and thrombocytopenia, 90% anemia), GI (88% diarrhea, 72% nausea, 42% vomiting) and metabolic (30-96% derangement in electrolytes), and similar to historical controls receiving HDM alone. Second malignancies were noted in 2 patients. Conclusions: HDLEN/HDM is a well tolerated and effective conditioning regimen for ASCT in patients with RRMM. This regimen merits further investigation as ASCT is likely to remain an integral part of the treatment of RRMM patients, yet few advancements have been made to this modality. HDLEN may be particularly useful in patients with high risk disease and those progressing after multiple lines of therapy. HDLEN added little toxicity to HDM and SPMs were not more frequent than expected per SEER database for patients in this age range. Clinical trial information: NCT01054196. [Table: see text]

Immunotherapy with Rituximab after Peripheral Blood Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5232-5232
Author(s):  
Celso Mitsushi Massumoto ◽  
Edilson Pinheiro Junior ◽  
Otávio C.G. Baiocchi ◽  
Ronald Pinheiro ◽  
Adelson Alves
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Clinical Characteristics ◽  
Residual Disease ◽  
High Dose

Abstract Introduction: autologous stem cell transplantation is a potentially curative or may augment the time to progression in Multiple Myeloma (MM) patients. The immunotherapy with rituximab may help control the minimal residual disease after high dose chemotherapy. Twenty percent (20%) of Multiple Myeloma patients express the CD20+ protein and can be target for immunotherapy. Objective: The aim of this study was to evaluate the use of rituximab after autologous stem cell transplantation for Multiple Myeloma. Patients and Methods: eight patients (4 male) with a median age of 53 (range 43–59) years diagnosed with MM. All of them had received at least one previous regimen were enrolled in the protocol study. All patients signed the consent form. Patients in relapse received a salvage regimen with C-VAD n=2 (cyclofosfamide 4 g/m2 e vincristine 0.4 mg/d (d 1–4), doxorrubicin 0.9 mg/m2 (d1-4) e dexametasone 40 mg (d1-4; 9-12; 17–22) or cyclofosfamide (1OO mg/kg, n=7) followed by stem cell harvesting. The preparative regimen was Busulfan 12 mg/kg and cyclofosfamide 120 mg/kg or Melphalan 200mg/m2. Rituximab at a dose of 375mg/m2 weekly x 4 was given every 6 months for 2 years after SCT. The clinical characteristics of the patients are shown on Table 1. Results: the median time to ANC and platelets engraftment was 11 (range 8–12) and 26 (range 17–35) days. Patients have been in CR at a median time of 11 months follow-up. Minor Rituximab-associated toxicities were seen:rigor, fever and short of breath that were controlled with acetaminophen and diphenidramine. Conclusion: the Rituximab given after autologous stem cell transplantation is safe in Multiple Myeloma patients and may prolong time to disease progression. A randomized study is required to evaluate the role of rituximab after ASCT. Table 1 - Clinical Characteristics of Patients Patients Age/gender Status Pre- BMT Status Post- BMT Salvage Tx Prep. regimen ANC/Platelets X1000 MM3/ml Follow-up (months) FRC 57/M PR PR C-VAD BU+MEL 12/28 EXPIRED MB 52/F CR1 CR1 C-VAD BU+MEL 12/60 EXPIRED AM 52/F PR PR C-VAD BU+MEL 9/26 EXPIRED IM 54/M PR CR Cyx2 BU+MEL 12/21 ALIVE GAD 50/F PR CR Cyx2 BU+MEL 12/35 ALIVE SCM 59/M CR CR Cyx2 BU+MEL 10/17 ALIVE MAD 63/F CR CR C-VAD MELPHALAN 12/25 ALIVE JFC 51/M CR CR C-VAD BU+MEL 12/18 ALIVE

Third Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4548-4548
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Maialen Lasa ◽  
Osman Ahmed ◽  
Marco Bua ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation—An Important Step Toward Improving Survival in Multiple Myeloma

2010 ◽  
Vol 06 ◽  
pp. 24
Author(s):  
Ajay Gupta ◽  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Response Rates ◽  
Major Advance

Conventional chemotherapy has been used in the treatment of multiple myeloma; however, the development of autologous stem cell transplantation (ASCT) represented a major advance in the therapy. Complete response (CR) rates of 40–45% were seen and this translated into improvements in progression-free survival (PFS) and overall survival (OS) in some studies. As a result, ASCT is the standard of care in eligible patients and can be carried out with low treatment-related mortality. The introduction of newer agents such as thalidomide, lenalidomide, bortezomib, and liposomal doxorubicin into induction regimens has resulted in higher CR rates, very good partial response rates (VGPR), and improvements in the ease of administration. These drugs have also proved useful in patients with adverse cytogenetics. Recent trials suggest that this has translated into improvements in response rates post-ASCT. There is a suggestion that patients achieving CR/near-CR (nCR) or VGPR after induction therapy should be placed on maintenance and ASCT could then be used as a treatment strategy at relapse; however, all of these trends await confirmation from further trials. Tandem transplants have been used to augment the results obtained with ASCT and have demonstrated their utility in patients who achieved only a partial response or stable disease in response to the first transplant and patients with adverse cytogenetics. Incorporation of bortezomib along with melphalan into the conditioning regimen has also been tried. It is hoped that recent advances in therapy will contribute greatly to improved survival.

Poor Mobilization of CD34+ Stem Cells Predicts Inferior Relapse and Survival Outcomes After Autologous Stem Cell Transplantation for Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3000-3000 ◽  
Author(s):  
Aleksandr Lazaryan ◽  
Hien Duong ◽  
Lisa Rybicki ◽  
Frederic J. Reu ◽  
Robert Dean ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Performance Status ◽  
Hematopoietic Stem

Abstract Abstract 3000 Autologous stem cell transplantation (ASCT) remains the standard upfront therapy of younger patients with multiple myeloma (MM). Identifying a prognostic threshold amount of mobilized CD34+ hematopoietic stem cells (SC) may become an important modifiable parameter in the era of novel stem cell mobilization strategies. While poor mobilization of CD34+ cells has been shown to cause delays in hematopoietic recovery, the data on long-term clinical outcomes of patients with inferior CD34+ SC collection (‘under mobilizers’) are limited. We analyzed prospectively collected data on 239 adult patients with MM who underwent ASCT at our institution from 01/1996 to 12/2009. Fifty-one patients (21.3%) who collected less than 4 × 106/kg CD34+ SC were classified as ‘under mobilizers’ and were compared to the rest of the study population (n=188) who collected ≥ 4 × 106/kg CD34+ SC. Even though under mobilizers were slightly older (median 59 vs. 54 years, p =0.01), had longer time from diagnosis to ASCT (11 vs. 8 months, p =0.05), and required more days of leukapheresis (5 vs. 3 days, p <0.001), they did not differ from the other group according to the number of prior treatment regimens, mobilization method (only 2 patients received plerixafor), performance status, or disease remission status at transplant (all p >0.2). Median time-to-recovery for both neutrophils (11 vs. 10 days, p <0.001) and platelets (13 vs. 12 days, p <0.001) was delayed among under mobilizers. Under mobilizers had worse relapse-free survival (RFS) (hazard ratio [HR]=1.49, 95% CI, 1.03–2.16, p =0.03) and non-relapse mortality (NRM) (HR=3.59, 95% CI, 1.51–8.56, p <0.01) in multivariable Cox proportional hazards analysis. Even though the association between poor CD34+ SC collection and inferior overall survival did not reach statistical significance (HR=1.42, 95% CI, 0.94–2.16, p =0.1), under mobilizers were found to have significantly higher rates of 100-day post-transplant mortality (p =0.02). We conclude that in the context of ASCT for MM, failure to collect ≥ 4 × 106/kg CD34+ SC is independently associated with worse RFS and NRM. Disclosures: No relevant conflicts of interest to declare.

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