Ten Year-Long Term Survival After up-Front Autologous Stem Cell Transplantation in Multiple Myeloma: Results From Two Prospective Clinical Trials

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 594-594
Author(s):  
Elena Zamagni ◽  
Francesco Di Raimondo ◽  
Francesca Patriarca ◽  
Patrizia Tosi ◽  
Annalisa Pezzi ◽  
...  

Abstract Abstract 594 Survival of patients with multiple myeloma (MM) has been extended with the introduction of autologous stem cell transplantation (ASCT). More recently, availability of highly effective novel agents has further improved patient outcomes. However, it is still the matter of debate whether a proportion of patients treated with ASCT can enjoy a long term survival, while sustaining prolonged high quality response. To address this issue and to identify those variables which were related to long-term survival, we performed a post-hoc analysis of two large prospective clinical trials of ASCT in newly diagnosed MM patients, the first one comparing single versus double ASCT and the second one incorporating thalidomide-dexamethasone (TD) into double ASCT. A total of 321 patients were randomly assigned in the first study to receive either a single or double ASCT, as previously described (Cavo M et al, JCO 2007). Three hundred and fifty seven patients were enrolled in the subsequent multicenter phase 2 study incorporating TD from the outset until the second ASCT; details of the protocol were previously reported (Cavo et al, J. Clin. Oncol 2009). Results were updated as of 30 March 2012 and compared with those previously reported. All the analyses were performed on an intention-to-treat basis. After a median follow-up of 61 months for the entire treatment population of the first study, PFS remained significantly longer with tandem versus single ASCT (median 37 vs 25 months, P= 0.012), while OS was similar in the two groups (median 71 vs 67 months). 47% and 33% of the patients in the double and single ASCT group achieved a CR+nCR (P= 0.008). Overall, in 24% and 11% of the patients, CR+nCR was sustained for more than 5 and 10 years, respectively. In a multivariate Cox regression analysis, best response (CR+nCR) ever achieved was the most important variable significantly extending PFS (P= 0.003) and OS (P=0.050); random assignment to double ASCT was an additional variable predicting for prolonged PFS(P= 0.026). After a median follow-up of 84 months from starting TD in the second study, median values of PFS and OS were 47.2 and 109.6 months, respectively. The final rate of CR+nCR was 34%, which was maintained for a median of 53 months. Overall, in 42.1% and 9.1% of the patients CR+nCR was sustained for more than 5 and 8 years, respectively. On multivariate analysis, failure to ever achieve at least CR+nCR, low Hb, high β2-m and t(4;14)±del(17p) were found to be independent variables predicting for poorer outcomes. In particular, a shorter OS was seen for patients ever lacking high-quality responses (HR: 0.35, 0.23–0.54, p<0.0001) and with t(4;14)±del(17p) (HR: 0.51, 0.33–0.79, p=0.0030). Overall, 23% and 20% of patients in the first and second study were alive over 10 or 8 years, respectively (long-term survivors). Median PFS of long-term survivors in the 2 studies were 74 and 87.7 months, respectively, versus 25 and 37 months for the rest of the population (P= 0.0000). Median duration of CR+nCR were 70 and 78 months in the long-term survivors group for the first and second study, respectively, in comparison with 21 and 49 months in the remaining patients (P<0.001 for both). The 10 and 8-year estimates of OS after relapse or progression in the long-term survivors of the two protocols were 58% and 72%, respectively, in comparison to a median value of 24 and 23 months for the control group (p<0.0001 for both). In a logistic regression analysis, attainment of high-quality responses was independently associated with long-term survival in both the studies (first study: OR: 1.8, 1.06–3.01, P= 0.03; second study: OR: 4.3, 2.17–8.60, P= 0.000). In conclusion, although the comparison between TD incorporated into ASCT and ASCT without thalidomide was not directly addressed by this analysis, TD + ASCT was associated with extended PFS and OS. Approximately 20% of the patients undergoing up-front ASCT can achieve long term survival (8–10 years from start of treatment), with 33% of them remaining relapse free. Attainment of sustained high-quality responses was the leading independent variable predicting for long-term OS. Prolonged survival after relapse was a contributing factor to long-term OS. Disclosures: Off Label Use: One of the 2 protocols discussed includes the use of thalidomide as induction prior to ASCT.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4560-4560
Author(s):  
Betsy R. Adams ◽  
Kevin McElligott ◽  
Laura Milligan ◽  
Luciano J Costa ◽  
Robert K Stuart

Abstract Abstract 4560 Introduction: About 15% of acute myelogenous leukemia (AML) patients will have disruption of the core binding factor (CBF) transcription factor as indicated by the detection of t(8;21) or inv(16) on metaphase cytogenetic analysis. In general, patients with CBF-AML are younger and regarded as having a favorable outcome when treated with anthracycline-based induction chemotherapy and multiple cycles of high-dose cytarabine consolidation. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) are usually perceived as unnecessary in the management of CBF-AMLs. However, most data indicating the favorable prognosis of CBF-AML with non-HSCT management originates from young selected patients participating in clinical trials and information on relapse treatments is often lacking. We performed a retrospective analysis of consecutive patients diagnosed with CBF-AML at a regional leukemia center over the last twelve years to assess long term survival of unselected patients and the likelihood of therapeutic success without ever requiring HSCT. Methods: The study cohort was identified through a search of all AML reports issued by the institutional clinical cytogenetics laboratory since the introduction of electronic records (1998-2010). We subsequently reviewed the charts of all patients with CBF-AML (irrespective of other cytogenetic abnormalities) to extract demographic, treatment, and outcome information. Survival status and subsequent treatments in other institutions were determined by contacting the patient, attending physician or review of public death records. Data collection and analysis were approved by the Institutional Review Board. Results: Thirty patients with CBF-AML were identified, 14 with t(8;21) and 16 with inv(16) AML. Median follow up for survivors in this series is 35.3 months (range 6.4–117.4) with all survivors currently in remission. Median age at diagnosis was 43 years (range 18–69) with 10 (33%) patients older than 55. All patients initially received therapy with curative intent with anthracycline-based induction chemotherapy. Only 47% of the patients were treated on clinical trials. There was 1 death during induction therapy and 22/29 patients (73.3%) achieved a complete remission with initial induction therapy. Overall 13 patients (43.3%) have required some modality of HSCT. Six patients received HSCT in CR1 due to perceived high risk of relapse (5 autologous, 1 allogeneic). None of the 6 patients who underwent HSCT in CR1 (5 autologous, 1 allogeneic) have relapsed. Among the 16 patients receiving non-transplant consolidation in CR1, 6 have subsequently relapsed and required a HSCT (3 autologous, 3 allogeneic) and 3 of these patients are alive 20.9–117.4 months from the initial diagnosis. Seven patients received HSCT in CR2 or in relapse (4 autologous, 3 allogeneic) and 6 of these patients are long-term survivors. Estimated 5 year overall survival for the entire cohort is 58.8 +/− 10.8%, comparable to what has been described for younger patients entering clinical trials (Grimwade et al, 2010). However, the likelihood of survival at 5 years without requiring HSCT was only 28.1+/− 8.8% (Figure). Conclusions: The favorable outcome previously reported for CBF-AMLs was reproducible in unselected patients. However, only a minority of patients were long term survivors relying exclusively on conventional chemotherapy. In the near future, strategies for molecular risk stratification of CBF-AML patients need to be coupled with risk-adapted therapy, likely including early use of HSCT for high-risk patients. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 166 (4) ◽  
pp. 616-618 ◽  
Author(s):  
Marie-Christiane Vekemans ◽  
Lucienne Michaux ◽  
Eric Van Den Neste ◽  
Augustin Ferrant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2091-2091
Author(s):  
Maximilian Schinke ◽  
Inga Promny ◽  
Stefanie Hieke ◽  
Johannes M. Waldschmidt ◽  
Gabriele Ihorst ◽  
...  

Abstract Introduction: Disease monitoring based on genetics or other molecular markers obtained by noninvasive or minimally invasive methods will potentially allow the early detection of treatment response or disease progression in cancer patients. Investigations in order to identify prognostic factors, e.g. patient's baseline characteristics or molecular markers, contributing to long-term survival potentially provide important information for patients with multiple myeloma. Overall survival (OS) is not very informative for patients who already survived one or more years. To better characterize long-term survival respectively long-term survivors, conditional survival (CS) analyses are useful. Conditional survival (CS) describes probabilities of surviving t additional years given they survived s years and provides information, how prognosis evolves over time. We have demonstrated the use of CS in a large data set of multiple myeloma patients with long-term survival which is mandatory for the calculation of CS (Hieke,... Engelhardt, Schumacher. CCR 2015). Methods: We evaluated 816 consecutive multiple myeloma patients treated at our department from 1997 to 2011 with follow-up until the end of 2011. Patients' data were assessed via electronic medical record (EMR) retrieval within an innovative research data warehouse. Our platform, the University of Freiburg Translational Research Integrated Database Environment (U-RIDE), acquires and stores all patient data contained in the EMR at our hospital and provides immediate advanced text searching capacity. We assessed 21 variables including gender, age, stage and admission period. We calculated 5-years CS and stratified 5-years CS according to disease- and host-related risks. Component-wise likelihood-based boosting and variables selected by boosting were investigated in a multivariable Cox model. Results: The OS probabilities at 5- and 10- years were 50% and 25%, respectively. The 5-year CS probabilities remained almost constant over the years a patient had already survived after initial diagnosis (~50%). According to baseline variables, conditional survival estimates showed no gender differences. The estimated 5-year survival probabilities varied substantially, from 25% for patients ages 70 or older to 65% for patients younger than 60 years. Similarly, patients with D&S stage I have an estimated 5-year survival probability of about 75% compared with 40% for patients with D&S stages II and III. Significant risk factors via Cox proportional hazard model were D&S stage II+III, age >70 years, hemoglobin <10g/dl, ß2-MG ≥5.5mg/dl, LDH ≥200U/l. Renal impairment, low albumin and unfavorable cytogenetics increased the risk, but failed to reach significance. Cytogenetics, response, response duration and other risk parameters post treatment are currently included in our assessment. Of note, over the study period, admission of patients <60 years decreased from 60% to 34%, but increased for those ≥70 years from 10% to 35%, respectively, illustrating that not only young and fit, but also elderly patients are increasingly treated within large referral and university centers and that patient cohorts and risks do not remain constant over time. Conclusions: Conditional survival has attracted attention in recent years either in an absolute or relative form where the latter is based on a comparison with an age-adjusted normal population being highly relevant from a public health perspective. In its absolute form, conditional survival constitutes the quantity of major interest in a clinical context. We defined conditional survival by using the fact that the patient is alive at the prediction time s as the conditioning event. Alternatively, one could determine conditional survival, given that the patient is alive and progression-free or alive, but has progression at time s (Zamboni et al. JCO 2010). Analysis of the above and additional variables from diagnosis to prediction time s may refine conditional survival towards an even more specifically determined prognosis; follow-up response and risk parameters most likely further refining these CS analyses. Figure 1. Figure 1. Disclosures Wäsch: MSD: Research Funding; Janssen-Cilag: Research Funding; Comprehensiv Cancer Center Freiburg: Research Funding; German Cancer Aid: Research Funding.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sonia Pértega-Díaz ◽  
Vanesa Balboa-Barreiro ◽  
Rocío Seijo-Bestilleiro ◽  
Cristina González-Martín ◽  
Remedios Pardeiro-Pértega ◽  
...  

Abstract Background Improved colorectal cancer (CRC) survival rates have been reported over the last years, with more than half of these patients surviving more than 5 years after the initial diagnosis. Better understanding these so-called long-term survivors could be very useful to further improve their prognosis as well as to detect other problems that may cause a significant deterioration in their health-related quality of life (HRQoL). Cure models provide novel statistical tools to better estimate the long-term survival rate for cancer and to identify characteristics that are differentially associated with a short or long-term prognosis. The aim of this study will be to investigate the long-term prognosis of CRC patients, characterise long-term CRC survivors and their HRQoL, and demonstrate the utility of statistical cure models to analyse survival and other associated factors in these patients. Methods This is a single-centre, ambispective, observational follow-up study in a cohort of n = 1945 patients with CRC diagnosed between 2006 and 2013. A HRQoL sub-study will be performed in the survivors of a subset of n = 485 CRC patients for which baseline HRQoL data from the time of their diagnosis is already available. Information obtained from interviews and the clinical records for each patient in the cohort is already available in a computerised database from previous studies. This data includes sociodemographic characteristics, family history of cancer, comorbidities, perceived symptoms, tumour characteristics at diagnosis, type of treatment, and diagnosis and treatment delay intervals. For the follow-up, information regarding local recurrences, development of metastases, new tumours, and mortality will be updated using hospital records. The HRQoL for long-term survivors will be assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. An analysis of global and specific survival (competitive risk models) will be performed. Relative survival will be estimated and mixture cure models will be applied. Finally, HRQoL will be analysed through multivariate regression models. Discussion We expect the results from this study to help us to more accurately determine the long-term survival of CRC, identify the needs and clinical situation of long-term CRC survivors, and could be used to propose new models of care for the follow-up of CRC patients.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3226-3226
Author(s):  
Eli Muchtar ◽  
Morie A. Gertz ◽  
Martha Q. Lacy ◽  
David Dingli ◽  
Francis K. Buadi ◽  
...  

Abstract Introduction: Prognosis of AL amyloidosis has improved in recent years; however for many patients prognosis remains poor. We aimed to define patient-, disease- and treatment characteristics which are associated with long-term survival. Method: A retrospective chart review of all patients with biopsy-proven systemic AL amyloidosis, who were seen within 90 days of the confirmed diagnosis. Long-term survival was defined as 5-year and 10-year survival from the time of diagnosis. For 5-year survival we selected patients seen between January 1, 2000 and December 31, 2012 (allowing a minimum of 5-year follow-up, n=1331) and for 10-year survival we screened patients seen between January 1, 2000 and December 31, 2007 (allowing a minimum of 10-year follow-up; n=779). Treatment allocation was defined as the first regimen given, irrespective of subsequent treatment modifications. Results: Of the screening population, 498 patients survived ≥5 years from diagnosis (37% of the 5-year screening cohort) and 168 patients survived 10 years or more (22% of the 10-year screening cohort). Five-year survivors and 10-year survivors as compared to their counterparts were (Table): younger, higher proportion of women, more likely to have single organ involvement, less heart/liver/nerve involvement and more kidney involvement. Long-term survivors also had lower bone marrow plasma cell percentage at the time of diagnosis and lower tumor burden measured by the difference between involved to uninvolved light chain (dFLC). Similarly, long-term survivors had lower Mayo stages and higher systolic blood pressure. No difference in light chain isotype was observed between long-term survivors to long term non-survivors. Long-term survivors were less likely to be seen within 30 days of diagnosis compared to their counterparts (52% among 5-year survivors vs 67% among 5-year non-survivor; P<0.001). FISH abnormalities (data available for 555/1331 patients, 42%) were comparable between groups with regard to t(11;14) (50% among 5-year survival compared to 50% among 5-year non-survivors; P=0.93) and 13q abnormalities (34% vs 36%, respectively; P=0.53). However, trisomies were less frequently encountered in the 5-year survivor group (20% vs 29%, respectively; P=0.01), and far less common among 10-year survivors (11% vs 26%, respectively; P=0.04). Autologous stem cell transplantation (ASCT) was more likely to be associated with long-term survival. Of all patients who underwent ASCT, 74% survived more than 5 years and 49% survived more than 10 years. In comparison, among the standard-intensity therapies, 5-year survival rates for melphalan-dexamethasone, bortezomib-based regimens, immunomodulatory drug-based regimens and single agent dexamethasone/ melphalan-prednisone were 29%, 28%, 30% and 10%, respectively. The corresponding 10-year survival rates were 15%, 20%, 20% and 5%, respectively. Conclusions: Long-term AL survivors have distinct favorable baseline characteristics (including those introduced by referral bias) and ASCT as their initial therapy. Identification of these patients, especially the Mayo 2004 stage III and the Mayo 2012 stage III-IV patients who unexpectedly survived 10 years, will allow for further study and insights. Disclosures Gertz: Teva: Consultancy; Prothena: Honoraria; Alnylam: Honoraria; celgene: Consultancy; Ionis: Honoraria; Physicians Education Resource: Consultancy; Research to Practice: Consultancy; Amgen: Consultancy; janssen: Consultancy; Apellis: Consultancy; Medscape: Consultancy; Abbvie: Consultancy; spectrum: Consultancy, Honoraria; annexon: Consultancy. Lacy:Celgene: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Russell:Vyriad: Equity Ownership. Kumar:KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 175-175 ◽  
Author(s):  
M. A. Gubens ◽  
P. L. Kunz ◽  
G. A. Fisher ◽  
J. M. Ford ◽  
D. Lichtensztajn ◽  
...  

175 Background: Pancreatic cancer is one of the most lethal malignancies, with an estimated 5-year survival rate of 6%, often due to advanced stage at diagnosis. However, there is a small population of patients, even with metastatic disease, who survive 3 years and beyond. Methods: Cases of pancreatic adenocarcinoma diagnosed from 1998 to 2005 were identified in the California Cancer Registry. A multivariate logistic regression model was constructed to predict the outcome of 3+ year survival according to demographic, disease and treatment variables defined a priori: age, gender, race/ethnicity, socioeconomic status (SES), histology, stage, treatment within 4 months of diagnosis (surgery, chemotherapy, and/or radiation), prior cancer history, and treatment at an academic hospital. Results: Among 54,475 cases of pancreatic cancer with ≥3 years of follow-up data available, median survival was 3.5 months. 2,855 patients (5.2%) survived at least 3 years, of whom 19% had remote stage disease at diagnosis. On multivariate analysis, advanced age was associated with decreased odds of long-term survival (p<0.01). By race, Asian/Pacific Islanders (odds ratio (OR) 1.76, p<0.01), Hispanics (OR 1.29, p=0.01) and non-Hispanic blacks (OR 1.24, p=0.14) were more likely to be long-term survivors than non-Hispanic whites. There was a gradient toward increased long- term survival for patients with higher SES (OR 1.49 for highest vs. lowest quintile, p<0.01). Mucinous tumors were associated with higher long-term survival than other adenocarcinomas (OR 2.21, p<0.01). Localized (OR 6.82) and regional stage disease (OR 2.61) showed more long-term survival than remote stage disease, both p<0.01. Surgery (OR 8.20, p<0.01), chemotherapy (OR 1.44, p<0.01), and radiation therapy (OR 1.25, p=0.02) increased the odds of long-term survival, as did treatment at an academic hospital (OR 1.54, p<0.01). Conclusions: In a well- characterized population-based registry with rigorous follow-up, we were able to identify a cohort of long-term survivors of pancreatic adenocarcinoma as well as factors associated with their exceptional survival. Planned future work with this cohort includes case-control studies making use of tumor and germline specimens, as well as survivorship research. No significant financial relationships to disclose.


1993 ◽  
Vol 14 (5) ◽  
pp. 416 ◽  
Author(s):  
Margaret C. Haugh ◽  
Catherine Cornu ◽  
Jean-Pierre Boissel

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5522-5522
Author(s):  
Florence Sabirou ◽  
Gautier Defossez ◽  
Pierre Ingrand ◽  
Isabelle Azais ◽  
Geraldine Durand ◽  
...  

Background: The treatment revolution of multiple myeloma (MM) with the advent of novel therapies, proteasome inhibitors, immunomodulators and newer drugs lead to increased survival. Clinical characteristics at diagnosis of Long-term survivor (>5 years after the start of treatment) were described; however data regarding the profile of lines of treatment is very limited. The aim of this study was to describe the profiles of response of this population. Methods: The Poitou‐Charentes cancer registry has exhaustively registered incident cases of MM from 2008 to 2010. The follow-up date was December 31st, 2018. Patients (pts) alive after 5 years from the start of first line treatment were considered long-term survivors and their data were collected from their medical files. Three pts profiles were studied, very long responder (VLR) treated with a single line; long responder (LR) treated with [2-3] lines; and advanced (AdMM) [4 lines +[. Smoldering Myeloma, AL amyloidosis, lost to follow-up pts were excluded from the analysis. Results: Among the 396 MM registered, 177 were alive after 5 years, and 158 were included in the study. The mean age was 62.3 +/-11, sex ratio 1.2, 51% IgG, 25% IgA and 20% Light Chain isotype. ISS1 was 42%, 34% ISS2 and 14% ISS3. The median follow-up after the 5-year landmark was 39.9 +/-13 months and 52% pts died during follow-up. Overall, the median number of lines was 2.9 +/-2, 44% had at least one ASCT, 83% received Bortezomib, 72% Lenalidomide, 48% Thalidomide, 22% Pomalidomide, 20% Daratumumab (usually 3 lines+). VLR represented 19%, 27% LR, and 54% AdMM. In VLR group, 43% received a Bortezomib-based regimen (2 or 3 drugs) followed by ASCT, 47% a Melphalan-based regimen plus Thalidomide (MPT) or Bortezomib (MPV). In LR group, first line comprised: 39% Bortezomib-based regimen and ASCT versus 24% MPT and 15% MPV. Second line for LR group: 75% had Lenalidomide single agent or combination, 22% had a Bortezomib-based regimen, 17% had an ASCT. In the LR group, 45% received a third line: 40% Lenalidomide, mostly single agent, 25% a Bortezomib-based regimen and 3% had an ASCT. The AdMM group had a mean of 5.9 +/-1.6 lines (range 4 -11) and 56% of RR patients had at least one ASCT. Conclusion: Approximately 40% of MM were long-term survivors at 5 years from start of therapy in 2010, mainly on the basis of proteasome inhibitors and immunomodulators-based regimens plus use of ASCT. The vast majority of pts reached the 5 years cut-off with [4;+[ lines, and very few pts were real long-term survivors with an early prolonged control of Myeloma. Future perspective will look into 10 years long-term survival, including novel drug developments with the advent of immunotherapy. Disclosures Sabirou: AbbVie: Research Funding. Leleu:Janssen: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Merck: Honoraria; BMS: Honoraria.


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