scholarly journals Autologous Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Drug Induction: A Retrospective Single-Center Analysis

2017 ◽  
Vol 137 (3) ◽  
pp. 163-172 ◽  
Author(s):  
Gabriela B. Thoennissen ◽  
Dennis Görlich ◽  
Ulrike Bacher ◽  
Thomas Aufenberg ◽  
Anne-Christin Hüsken ◽  
...  

Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (n = 286) or tandem (n = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (p = 0.03) and stage 3 according to the International Staging System (p = 0.006) as adverse risk factors regarding PFS. Median OS was significantly better in newly diagnosed MM patients receiving induction therapy with novel agents, e.g., bortezomib, thalidomide, or lenalidomide, compared with a traditional regimen (69 vs. 58 months; p = 0.01). More patients achieved at least a very good partial remission in the period from 2005 to 2012 than from 1996 to 2004 (65 vs. 30%; p < 0.001), with a longer median OS in the later period (71 vs. 52 months, p = 0.027). In conclusion, our analysis confirms HDCT-ASCT as an effective therapeutic strategy in an unselected large myeloma patient cohort with a low TRD rate and improved prognosis due to novel induction strategies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19532-e19532
Author(s):  
Taner Demirer ◽  
Guldane Cengiz Seval ◽  
Selami Kocak Toprak ◽  
Sinem Civriz Bozdag ◽  
Meltem Kurt Yuksel ◽  
...  

e19532 Background: High dose melphalan and autologous stem cell transplantation (ASCT) significantly prolong survival for patients with multiple myeloma (MM). The purpose of this study is to assess the effects of hemoglobin (Hgb) and serum creatinine (Crea) values at the time of transplantation on the overall outcome of patients with multiple myeloma treated at our transplant center. Material & Methods: This analysis included 247 consecutive patients who underwent ASCT for MM between 2010-2016. Hemoglobin was grouped as low or high relative to their sample median. Patients were also stratified according to serum Crea value at the time of transplantation ( < 2 or ³2 mg/dl). Results: The median age was 57 (29-75) years and most patients were male (n = 151, 61.1%), IgG subtype (n = 124, 50.2%), and ISS stage 3 (n = 122, 49.4%). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). The most commonly induction regimens included VAD (vincristine, doxorubicin and dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone), respectively. Since maintenance was not an approved treatment in myeloma most patients did not receive any. For the entire cohort, the median Hgb and Crea were 11.5 g/dL and 0.9 mg/dL respectively. No difference in progression free survival (PFS) was observed between a lower and higher Hgb (82 vs. 81 months, p = 0.96). However, the median PFS was significantly longer in patients with a lower Crea compared to those with a higher Crea (83 vs. 48 months, p = 0.01). Patients with both a lower hemoglobin and higher Crea experienced shorter PFS compared to those with a higher hemoglobin and lower Crea (45 vs. 82 months, p < 0.001). We failed to demonstrate the impact of creatinin levels on time to neutrophil and platelet engraftment. There were no differences in OS according to lower vs. higher Hgb (58 vs. 52 months; p = 0.29, respectively) but in higher crea cohort worse OS was observed (41 months vs. 57 months; p = 0.02, respectively). Conclusions: We demonstrate that hemoglobin and creatinine represent important determinants of clinical outcomes after ASCT. A lower hemoglobin and higher creatinine, individually and when combined, were associated with shorter PFS. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant Hgb and Crea levels on ASCT outcomes.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2191-2191
Author(s):  
Anna Sureda ◽  
Carme Canals ◽  
Nicolas Mounier ◽  
Roberto Foa ◽  
Eulogio Conde ◽  
...  

Abstract Autologous stem cell transplantation (ASCT) remains the treatment of choice for patients (pts) with diffuse large B-cell lymphoma (DLBCL) that relapse after first line chemotherapy (CT). Nevertheless, the impact of the use of the anti-CD20 monoclonal antibody (Rituximab®) (RTX) with combination CT on the ulterior results of the transplantation procedure has to be determined. One of the main factors affecting survival after ASCT is a short first remission duration. This study was designed to evaluate the benefit of this strategy, in pts with DLBCL achieving after salvage CT a 2nd complete remission (CR2), by retrospectively comparing for each pt the progression free survival (PFS) after ASCT with the duration of the previous CR. Adult DLBCL pts with MEDB information available autografted in CR2 between 1990 and 2005 in EBMT centres were included in the analysis. A total of 386 pts (224 males, median age 47 (18–71) years] were evaluated. 294 pts (74%) did not receive RTX prior to ASCT, 67 pts (17%) did receive it at all and in 34 pts (9%) this information is missing. Duration of CR1 was 12 (3 – 142) months [median (range)]; it lasted less than 6 months in 25% of the cases and was longer than 24 months in 25% of the pts. Median time from diagnosis to ASCT was 25 (6–181) months. Peripheral blood was used as the source of hematopoietic stem cells in 311 pts (81%). The BEAM protocol was the conditioning regimen most frequently used (n = 244, 63%) and only 5.5% pts were conditioned with TBI-containing regimens. After a median follow up after ASCT for surviving pts of 42 months, overall survival (OS) was 63% and PFS 48%. 158 pts did relapse after ASCT [median (range), 10 (3–200) months] and 32 pts died from non-relapse mortality. When each patient was taken as her/his own control, PFS after ASCT was longer than CR1 (p &lt; 0.001). During the initial phase of the disease, 74% pts experienced 1st relapse in less than 2 years, compared with only 32% of the patients who experienced 2nd relapse 2 years after ASCT. The use of RTX prior to ASCT did not impair the beneficial effects of the autologous procedure in the whole population of pts (RTX no: 66% vs 33%, p &lt; 0.001; RTX yes: 73% vs 26%, p = 0.001). 2-years PFS after ASCT was significantly lower in patients with a CR1 &lt; 12 months (p &lt; 0.001). However, in this subgroup of patients PFS after ASCT was significantly longer than CR1 duration when studying each pt as his/her own control (p = 0.001). ASCT can significantly increase PFS in comparison with the duration of CR2 in DLBCL and can change disease course. The use of RTX prior to ASCT does not decrease the beneficial effect of pts autografted in CR2 when compared to their prior CR1 duration. The duration of CR1 remains one of the most important prognostic factors for ASCT outcome.


Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 12
Author(s):  
Shuji Ozaki ◽  
Takeshi Harada ◽  
Hikaru Yagi ◽  
Etsuko Sekimoto ◽  
Hironobu Shibata ◽  
...  

We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of serum IgG, IgA, and IgM 1 year after ASCT. Among 50 patients, 26 patients showed polyclonal Ig recovery; 14 patients were in ≥complete response (CR) and 12 remained in non-CR after ASCT. The patients with Ig recovery exhibited a significantly better progression-free survival (PFS, median, 46.8 vs. 26.7 months, p = 0.0071) and overall survival (OS, median, not reached vs. 65.3 months, p < 0.00001) compared with those without Ig recovery. The survival benefits of Ig recovery were similarly observed in ≥CR patients (median OS, not reached vs. 80.5 months, p = 0.061) and non-CR patients (median OS, not reached vs. 53.2 months, p = 0.00016). Multivariate analysis revealed that non-CR and not all Ig recovery were independent prognostic factors for PFS (HR, 4.284, 95%CI (1.868–9.826), p = 0.00059; and HR, 2.804, 95%CI (1.334–5.896), p = 0.0065, respectively) and also for OS (HR, 8.245, 95%CI (1.528–44.47), p = 0.014; and HR, 36.55, 95%CI (3.942–338.8), p = 0.0015, respectively). Therefore, in addition to the depth of response, the recovery of polyclonal Ig after ASCT is a useful indicator especially for long-term outcome and might be considered to prevent overtreatment with maintenance therapy in transplanted patients with MM.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1168-1168 ◽  
Author(s):  
Roland Fenk ◽  
Thorsten Graef ◽  
Ingmar Bruns ◽  
Leilani Ruf ◽  
Zohren Fabian ◽  
...  

Abstract High dose chemotherapy (HDT) with autologous stem cell transplantation has improved response rates and survival of patients with multiple myeloma. However the majority of patients suffer from relapse. Therefore, in this retrospective study we evaluated the impact of maintenance therapy with either thalidomide or interferon on the progression-free survival (PFS) after HDT and compared these results with a planned allogeneic transplant with reduced intensity conditioning (RIC) as consolidation therapy after HDT. We analysed 95 patients with a median age of 55 years who were treated at our institution in 2001–2005 with the diagnosis of stage III myeloma. Melphalan 200 mg/m2 was used as conditioning regimen followed by autologous stem cell transplantation. Interferon was given at a dose of 1.0 to 4.5 million U three times a week and the daily dose of thalidomide was 100 to 400 mg according to the individual tolerance of side effects. Allotransplants were performed with HLA-identical sibling donors after fludarabin 90 mg/m2 and TBI (2Gy) conditioning. In median 3.8 months after single HDT patients received either a RIC allotransplant (n=14) or maintenance therapy with thalidomide (n=39) or interferon (n=30) or no maintenance therapy (n=12). Prognostic factors such as cytogenetic abnormalities, beta-2 microglobulin, chemosensitive disease before HDT or remission status after HDT were equally distributed in all treatment groups. After a median follow-up of 33 months (range: 8–60) PFS from the start of treatment did not differ between patients after allotransplant (median not yet reached) and patients receiving thalidomide (median 50 months, p=0.8) but was significantly improved in comparison to patients who received interferon or no maintenance therapy (median 24 months, p&lt;0.0001). Most patients who received interferon or no maintenance therapy were treated with thalidomide at the time of relapse. Therefore, we also compared the combined PFS of patients treated with interferon maintenance followed by thalidomide in first relapse with the PFS of patients treated with immediate thalidomide maintenance therapy. Most interestingly, PFS of these two treatment schedules was not different (median 50 months in both groups; p=0.9), but the time of thalidomide exposure was in median 13 months shorter for patients in the interferon treatment arm. This is important, as to date most novel therapies hold the risk of polyneuropathy and thus pre-existing polyneuropathy due to prior thalidomide therapy limits the therapeutical options during the course of disease. Analysis of overall survival showed no differences between patients in the thalidomide or the interferon treatment arm (median not reached in both groups, p=0.5), but survival was inferior with RIC allotransplant (median 44 months, p=0.02). In conclusion, thalidomide is an effective maintenance therapy which prolongs PFS after single HDT. Interferon is less effective but the treatment schedule interferon maintenance therapy followed by thalidomide at the time of relapse is equal to upfront thalidomide maintenance therapy in terms of cumulative PFS and may be less toxic. RIC allotransplant is not superior to other treatment options and thus still has to be considered an experimental treatment option.


Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6063-6073 ◽  
Author(s):  
Michele Cavo ◽  
S. Vincent Rajkumar ◽  
Antonio Palumbo ◽  
Philippe Moreau ◽  
Robert Orlowski ◽  
...  

AbstractThe role of high-dose therapy followed by autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM) continues to evolve in the novel agent era. The choice of induction therapy has moved from conventional chemotherapy to newer regimens incorporating the immunomodulatory derivatives thalidomide or lenalidomide and the proteasome inhibitor bortezomib. These drugs combine well with traditional therapies and with one another to form various doublet, triplet, and quadruplet regimens. Up-front use of these induction treatments, in particular 3-drug combinations, has affected unprecedented rates of complete response that rival those previously seen with conventional chemotherapy and subsequent ASCT. Autotransplantation applied after novel-agent-based induction regimens provides further improvement in the depth of response, a gain that translates into extended progression-free survival and, potentially, overall survival. High activity shown by immunomodulatory derivatives and bortezomib before ASCT has recently led to their use as consolidation and maintenance therapies after autotransplantation. Novel agents and ASCT are complementary treatment strategies for MM. This article reviews the current literature and provides important perspectives and guidance on the major issues surrounding the optimal current management of younger, transplantation-eligible MM patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marc-Andrea Baertsch ◽  
◽  
Elias K. Mai ◽  
Thomas Hielscher ◽  
Uta Bertsch ◽  
...  

AbstractLenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with <nCR after first ASCT were assigned tandem ASCT in both trials. In patients with <nCR and tandem ASCT (LEN: n = 54 vs. BTZ: n = 84), LEN MT significantly improved PFS (HR = 0.61, p = 0.04) but not OS (HR = 0.46, p = 0.09). In conclusion, the significant PFS benefit after eliminating the impact of different tandem ASCT rates supports the current standard of LEN MT after ASCT.


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