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]

Multicenter Phase II Trial of 90Y-Ibritumomab Tiuxetan with High-Dose Chemotherapy (Busulfan/Cyclophosphamide/Etoposide) Followed by Autologous Stem Cell Transplantation in Relapsed, Refractoried, or High-Risk B-Cell NHL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1914-1914
Author(s):  
Byung Woog Kang ◽  
Jae-Cheol Jo ◽  
Shin Kim ◽  
Geundoo Jang ◽  
Sung Sook Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Ibritumomab Tiuxetan

Abstract The need of new effective regimen for high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in aggressive B-cell non-Hodgkin’s lymphoma (NHL) patients and promising results observed so far in trials with 90Y-Ibritumomab tiuxetan containing regimens in ASCT strongly warrants the investigation of 90Y-Ibritumomab tiuxetan combined busulfan/cyclophosphamide/etoposide (Z-BuCyE) high-dose chemotherapy with ASCT for relapsed, refractoried, or high-risk B-cell NHL. We evaluated efficacy and safety of the combination of Z-BuCyE and ASCT in patients with relapsed, refractoried, or high-risk B-cell NHL. Treatment consisted of two doses of Rituximab (250 mg/m2, IV, day -21, -14) and a single dose of 90Y-Ibritumomab (0.4 mCi/kg, IV, day -14). All patients received conditioning regimen: busulfan (3.2 mg/kg, IV, day -7, -6, -5), etoposide (200 mg/m2, IV, day -5, -4), and cytoxan (50 mg/kg, IV, day -3, -2) followed by ASCT (day 0). Thirteen patients were entered the trial. The median age was 46.1 years (range: 25–60), and 6 (46%) patients were male. Histology was diffuse large B-cell (n=10), follicular (n=1), Burkitt (n=1), and mantle cell lymphoma (n=1). The objective overall response rate (ORR) was 76.9% (10/13): continued CR, 38.5% (5/13); induced CR, 23.1% (3/13); continued or induced PR, 15.4% (2/13). Three patients (23.1%) had a PD after transplantation and two of these patients died of progression. Median follow-up duration was 6.0 months. Median progression-free survival (PFS) and median overall survival (OS) has not yet been reached. Toxicity was principally non-hematologic. Grade 2 toxicity included mucositis (53.8%), nausea (61.5%), vomiting (15.4%), diarrhea (23.1%), and elevation of liver enzyme (7.7%). Grade 3 toxicity included mucositis (15.4%), nausea (23.1%), and diarrhea (23.1%). There was no grade 4 toxicity. Infection occurred in ten patients, bleeding in one patient, and there was no treatment related mortality. This preliminary analysis shows that the combination of Z-BuCyE and ASCT has excellent efficacy and is well-tolerated treatments for relapsed, refractoried or high-risk B-cell NHL. This study will be continued till 20 patients enrollment.

scholarly journals Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study

2020 ◽  
Vol 8 (1) ◽  
pp. e000286 ◽  
Author(s):  
Benjamin A Derman ◽  
Yuanyuan Zha ◽  
Todd M Zimmerman ◽  
Rebecca Malloy ◽  
Andrzej Jakubowiak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Ex Vivo ◽  
Conditioning Regimen ◽  
High Dose ◽  
Treg Depletion ◽  
Post Transplant

BackgroundProgression after high-dose melphalan with autologous stem cell transplantation (ASCT) in multiple myeloma (MM) may be due in part to immune dysfunction. Regulatory T (Treg) cells reconstitute rapidly after ASCT and inhibit immune responses against myeloma cells.MethodsWe performed a randomized study to evaluate two methods of Treg depletion in patients with MM undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 monoclonal antibody (basiliximab 20 mg IV) was administered on day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. Tregs were depleted from autologous stem cell (ASC) grafts with anti-CD25 microbeads and the CliniMACS device in the ex vivo Treg depletion (EVTRD) arm.ResultsFifteen patients were enrolled, five in each arm. The conditioning regimen was melphalan 200 mg/m2. Primary objectives included assessments of efficiency of IVTRD/EVTRD, kinetics of Treg depletion and recovery following ASCT, and safety. EVTRD removed 90% of CD4+CD25+cells from ASC grafts. IVTRD and EVTRD led to reductions in Treg frequency between days +7 and +90 post-transplant compared with the control (p=0.007 and p<0.001, respectively).ConclusionsIVTRD and EVTRD are feasible and significantly reduce and delay Treg recovery post-ASCT for MM, and serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes.Trial registration numberNCT01526096.

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.

Sign in / Sign up

Export Citation Format

Share Document