Treatment of Persons with Multiple Myeloma in Underprivileged Circumstances: Real-World Data from a Single Institution

2020 ◽  
Vol 143 (6) ◽  
pp. 552-558 ◽  
Author(s):  
Iván  Murrieta-Álvarez ◽  
David P. Steensma ◽  
Juan Carlos Olivares-Gazca ◽  
Mauricio Olivares-Gazca ◽  
Andrés León-Peña ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Overall Survival ◽  
Low Cost ◽  
Novel Agents ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Real World Data ◽  
Term Survival

<b><i>Background:</i></b> The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally. <b><i>Patients and Methods:</i></b> All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were included in this study. Patients were given oral thalidomide (100 mg/day), oral dexamethasone (36–40 mg/week), and aspirin 100 mg/day. Bor­tezomib (1.75 mg s.c. every week) was administered to those who could afford it. After 4–6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following HCT, patients continued indefinitely on thalidomide; those who failed to tolerate thalidomide were switched to lenalidomide (25 mg/day). <b><i>Results:</i></b> The median overall survival (OS) for all patients has not been reached and is &#x3e;157 months. Median follow-up of the patients lasted 14 months (range 1.3–157). The median OS of patients with and without HCT was similar. The response rate (complete remission or very good partial remission) was 72% for those given thalidomide plus dexamethasone versus 88% for those given bortezomib, thalidomide, and dexamethasone before HCT, but OS was not different. As post-HCT maintenance, 37 patients received thalidomide; 26 of those (70%) could be maintained indefinitely on thalidomide, whereas 11 were switched to lenalidomide after a median of 7 months; median OS of patients maintained on thalidomide or lenalidomide after HCT was not different. <b><i>Conclusion:</i></b> In this series, a regimen incorporating low-cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of MM patients. This approach may be a model for MM treatment in underprivileged circumstances.

scholarly journals Treatment of Persons with Multiple Myeloma in Underprivileged Circumstances: Real-World Data of a Prospective Study in a Single Institution

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5707-5707
Author(s):  
Iván Murrieta-Álvarez ◽  
David P. Steensma ◽  
Juan Carlos Olivares-Gazca ◽  
Jesús Mauricio Olivares-Gazca ◽  
Andrés A. León-Peña ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Population Data ◽  
Mantel Test ◽  
Novel Agents ◽  
P Value ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Real World Data ◽  
Term Survival

Background The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally. Patients and methods All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were prospectively entered in this study. Patients were given oral thalidomide (T), 100 mg/day, oral dexamethasone (D) (36-40 mg/week) and aspirin 100 mg/day. Bortezomib (V) (1.75 mg subcutaneously every week) was administered to those who could afford it. After 4-6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following the HCT, patients continued indefinitely on T; those who failed to tolerate were switched to lenalidomide (R) (25 mg/day). The assessment of overall survival (OS) for all groups was achieved through the Kaplan-Meier method using the Cox-Mantel test. All the statistical analyses used a p value <0.05 to considered them statistically significant. Results Among 108 patients with MM who were prospectively accrued in the study (47 females and 61 males), the median age was 57 years (range 33 to 90). IgG myeloma represented 60% of patients and 49% had International Scoring System (ISS) stage III disease. The median (OS for all patients has not been reached and is >157 months. The median OS of patients who did not receive HCT was similar to those who did, with a trend for better outcomes with HCT (A). The response rate (complete remission or very good partial remission) was 71.8% for those given TD versus 88.3% for those given VTD before HCT, but OS was not different (B, C and D). As post-HCT maintenance, 37 patients received T; 26 of those (70%) could be maintained indefinitely with T, whereas 11 were switched into R after a median of 7 months; median OS of patients maintained after HCT with T or R was not different. Comparing the current population data with those obtained between 1983 and 1993 in the same institution employing only MP, the prognosis of MM patients was noted to have improved substantially. In our previous experience in the same institution, the median OS of patients treated solely with MP was 33 months, with a 72-month survival of 30%, whereas in this study of patients given IMiDs +/- HCT, median OS has not been reached and the 72-month OS is 60%, twice that obtained with MP. When analyzing the OS of patients included in this study and separated by 5-year intervals, survival continued to improve since 1993. Conclusions In this series, a regimen incorporating low cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of persons with MM. This approach may be a model for treatment of MM in middle-income countries. Figure Disclosures Steensma: Aprea: Research Funding; Arrowhead: Equity Ownership; Summer Road: Consultancy; Astex: Consultancy; Onconova: Consultancy; H3 Biosciences: Other: Research funding to institution, not investigator.; Stemline: Consultancy; Pfizer: Consultancy.

scholarly journals Narcotic Use in Multiple Myeloma Patients at the Time of ASCT and One-Year Follow up

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4726-4726
Author(s):  
Matthew Danish ◽  
Tabitha Copeland ◽  
Joseph Ho ◽  
Mansi Shah ◽  
Dennis Cooper
Keyword(s):  
Multiple Myeloma ◽  
Clinical Response ◽  
Bone Pain ◽  
Novel Agents ◽  
Cell Transplant ◽  
Post Transplant ◽  
Opiate Use ◽  
The Impact

Background: Bone pain is one of the most common presentations of multiple myeloma and nearly all patients have skeletal involvement in the course of disease. Consequently, many patients require narcotics for symptom management at the time of diagnosis but the long term impact of MM treatment on pain control remains uncertain. With the advent of combination therapy for MM with novel agents followed by transplant and then maintenance therapy, clinical response is nearly universal and greater than 30% of patients achieve a serologic complete response. Therefore, we examined the impact of modern myeloma-directed therapy and high response rates on the use of narcotics up to 1 year after transplant in this group of patients. Methods: A retrospective review of data collected from the Rutgers-CINJ database was conducted. All patients who received induction inducing therapy (e.g. bortezomib, lenalidomide and dexamethasone or cyclophosphamide, bortezomib and dexamethasone) followed by high dose melphalan and autologous stem cell transplant (ASCT) and who had adequate post-transplant follow up (at least 100 days) were included. Morphine use was assessed at the time of transplant and at follow-up visits. All opiates (e.g. oxycodone, fentanyl, MS contin, etc.) where converted to morphine equivalents/day (ME/day) and recorded. Treatment responses were determined based on the International Myeloma Working Group Response Criteria. We compared the incidence and amount of narcotic use over time using one-way analysis of variance (ANOVA) and Dunn's multiple-comparison test. Results: 189 patients were included in the analysis. 38% were using opiates at the time of transplant. At 100 days post-transplant 35.5% were using opiates and at 1 year post transplant 30.9% were using opiates (p=0.04) . Average opiate use was 74.1 ME/day (95% CI: 55.2 to 92.9), 69.45 ME/day (95% CI: 50.5 to 88.3), and 70.78 ME/day (95% CI: 43.5 to 98) for each of the aforementioned time points (p=0.088) (Figure 1). For example, 74 ME/day would be equal to approximately 50 mg of Oxycodone daily. 74 patients were active opiate users at the time of transplant (Table 1). Response to myeloma treatment (remission, progression, relapse) was not different in opiate-using patients at the time of transplant or at 100 days and 1 year after transplant (Table 2). Conclusion : Early studies from the 1960's reported on the rapid reduction of bone pain in treatment responsive patients with MM (Hogstrata et al.). Recently, treatment modalities for MM have significantly improved, leading to markedly increased remission rates (>90%), progression-free and overall survival. With dramatically increased serologic responses, one would hypothesize that there would be a decline in pain and a subsequent decrease in opiate use. However, in this retrospective chart review we found that 30% of multiple myeloma patients continued to use opiates following transplant and that ongoing use of opiates appeared to be independent of clinical response. Interestingly, at the time of transplant active opiate users had a CR of 27.2% while the non-opiate using patients had a CR of 13.3%. Although there was a slight decline in the number of opiate users at the 1 year follow up, 33% of opiate users continued at their original level of opiate use and 22% increased their opiate use at 1 year post ASCT. Persistent long term use of opiates is of particular concern given that the survival of patients with MM has significantly improved with the use of novel agents and autologous transplant with an increasing number of patients surviving 10 years or more. In patients who have achieved an excellent response (e.g. serologic CR and negative PET scan), ongoing narcotic use should be addressed at each visit and other advanced pain management techniques should be considered. Disclosures No relevant conflicts of interest to declare.

Long-Term Survival In Patients With Acute Steroid Refractory Graft-Versus-Host-Disease (SR-GVHD) Treated With Infliximab Combined With Daclizumab

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4624-4624
Author(s):  
Sanaz Nicky Soltani ◽  
Ramaprasad Srinivasan ◽  
Theresa Jerussi ◽  
A. John Barrett ◽  
Thomas E Hughes ◽  
...  
Keyword(s):  
High Probability ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Post Transplant

Acute SR-GVHD occurs in approximately 15% of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), and is associated with a 70-90% long-term mortality rate. We previously reported that concomitant blockade of TNF-α and IL-2 pathways with infliximab combined with daclizumab have a synergistic therapeutic effect, with a high probability of complete resolution of SR-GVHD. Although various treatment modalities are effective in the treatment of SR-GVHD, minimal long-term follow up data exists for complete responders to second line treatments. Here we report long-term outcomes in a cohort of 23 subjects developing SR-GVHD treated with infliximab/daclizumab. A consecutive series of 141 patients with a variety of hematological and non-hematological malignancies as well as nonmalignant hematological disorders including severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria and pure red cells aplasia, underwent a reduced intensity allogeneic HSCT from an HLA identical or single antigen mismatched relative at a single institution between 2/2001 and 12/2008. Transplant conditioning consisted of cyclophosphamide (60 mg/kg days -7, -6) and fludarabine (25 mg/m2days -5 to -1) with or without equine ATG or 6-12 Gy of total body irradiation. GVHD prophylaxis was with cyclosporine with or without additional MMF or MTX. Twenty three patients (median age 35 years, range 13-65 years) developed SR-GVHD at a median of 28 days post transplant. SR-GVHD was defined as absence of response to at least 6 days of high dose methylprednisolone therapy. Following a diagnosis of SR-GVHD, patients received a combination of daclizumab (1mg/kg given on days 1, 4, 8, 15, 22), infliximab (10mg/kg given on days 1, 8, 15, 22), broad spectrum bacterial and anti-fungal prophylaxis, and had their methylprednisolone tapered to 1mg/kg/day. Combined cytokine blockade was highly active against SR-GVHD, with 21/23 (87.5%) patients achieving a complete response (CR), defined as total resolution of GVHD in all involved organ systems. All complete responders survived to hospital discharge. With a median follow-up of 9 years (range 5-10 years), 9/23 (39%) survive, including 6 patients without chronic GVHD whose immunosuppressive therapy (IST) has been discontinued and 3 patients with chronic GVHD (2 limited and 1 extensive) who continue to be tapered off IST. Fourteen of 21 patients with resolution of SR-GVHD died a median 173 days post transplant (range 67-1039 days), including 1 from complications related to recurrent SR-GVHD, 6 from progression of malignancy (all solid tumors), 2 from bleeding related to peptic ulcer disease and 5 from infectious complications including invasive fungal infection and CMV disease. A subgroup analysis showed 5/6 patients with SAA developing SR-GVHD had a complete response to combined infliximab/daclizimab. Remarkably, at a median 6 years follow up, 67% (4/6) of these SAA patients were long-term survivors. All these survivors have maintained normal blood counts and remained transfusion independent with 100% donor chimerism in myeloid and T-cell lineages. Conclusion Patients with SR-GVHD treated with infliximab combined with daclizumab had a high probability of achieving a complete response with nearly 40% of patients having long-term survival. This is the first report to show that long-term survival can be achieved in a substantial proportion of patients receiving combined IL-2 and TNF blockade for SR-GVHD. Disclosures: Off Label Use: Infliximab is FDA approved for the treatment of psoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis. Daclizumab gained FDA approval for use in transplant rejection.

scholarly journals Feline and Canine Cutaneous Lymphocytosis: Reactive Process or Indolent Neoplastic Disease?

2022 ◽  
Vol 9 (1) ◽  
pp. 26
Author(s):  
Francesco Albanese ◽  
Francesca Abramo ◽  
Michele Marino ◽  
Maria Massaro ◽  
Laura Marconato ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Clinical Signs ◽  
Case Series ◽  
Response To Treatment ◽  
Neoplastic Disease ◽  
Retrospective Case ◽  
Term Survival ◽  
Dermal Infiltrate

Cutaneous lymphocytosis (CL) is an uncommon and controversial lymphoproliferative disorder described in dogs and cats. CL is generally characterized by a heterogeneous clinical presentation and histological features that may overlap with epitheliotropic lymphoma. Therefore, its neoplastic or reactive nature is still debated. Here, we describe clinicopathological, immunohistochemical, and clonality features of a retrospective case series of 19 cats and 10 dogs with lesions histologically compatible with CL. In both species, alopecia, erythema, and scales were the most frequent clinical signs. Histologically, a dermal infiltrate of small to medium-sized lymphocytes, occasionally extending to the subcutis, was always identified. Conversely, when present, epitheliotropism was generally mild. In cats, the infiltrate was consistently CD3+; in dogs, a mixture of CD3+ and CD20+ lymphocytes was observed only in 4 cases. The infiltrate was polyclonal in all cats, while BCR and TCR clonal rearrangements were identified in dogs. Overall, cats had a long-term survival (median overall survival = 1080 days) regardless of the treatment received, while dogs showed a shorter and variable clinical course, with no evident associations with clinicopathological features. In conclusion, our results support a reactive nature of the disease in cats, associated with prolonged survival; despite a similar histological picture, canine CL is associated with a more heterogeneous lymphocytic infiltrate, clonality results, and response to treatment, implying a more challenging discrimination between CL and CEL in this species. A complete diagnostic workup and detailed follow-up information on a higher number of cases is warrant for dogs.

scholarly journals Pre-Salvage ISS and Other Important Outcome Predictors in CD34 Selected Allogeneic Hematopoietic Cell Transplant for Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3473-3473
Author(s):  
Adam Bryant ◽  
Patrick Hilden ◽  
Sergio Giralt ◽  
Miguel-Angel Perales ◽  
Guenther Koehne
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Older Age ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Term Survival ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
The Impact

Abstract Introduction Despite recent therapeutic advances Multiple Myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to imid or proteasome inhibitor therapies are universally dismal.1 Allogeneic hematopoietic cell transplant (alloHCT) remains the only curative MM treatment but has been associated with historically high rates of GVHD and of non-relapse mortality (NRM), exceeding 40% in some series.2 Although these rates have decreased in recent years, the potential morbidity and mortality associated with alloHCT and the increasing availability of alternative non-transplant therapies demands a thoroughly informed pre-alloHCT assessment. Here we assess the impact of pre-alloHCT variables on clinical outcomes in a large cohort of relapsed/refractory (RR) MM patients who underwent CD34+ selected alloHCT at our institution. Methods This retrospective study included all MM patients who had CD34+ selected alloHCT from Jun 2010 to Dec 2015. Patients were conditioned with targeted dose busulfan (0.8 mg/kg x 10), melphalan (70 mg/m2 x 2) and fludarabine (25mg/m2 x 5) followed by infusion of a CD34+ selected peripheral blood stem cell graft, without post alloHCT GVHD prophylaxis. Estimates were given using the Kaplan-Meier and cumulative incidence methods. Competing risks for relapse, NRM, and GVHD were death, relapse, and relapse or death respectively. The log-rank and Gray's test were used to assess univariable associations. GVHD by 6 months was assessed via a landmark analysis. Results Our 73 patient cohort had a median age of 55 (37-66) and was mostly male (74%). Most patients had low risk MM by ISS (50/66, 76%) and intermediate risk MM by R-ISS (45/66, 68%) at pre-salvage assessment. Patients had a median of 4 (2-9) pre-alloHCT lines of therapy and were evenly split between patients in PR and in VGPR or CR at time of alloHCT (50% and 49%). Median HCT-CI score was 2 (range 0-6) with the majority of patients graded as intermediate or high risk (score ≥1; 55/73, 75%). At a median follow-up in survivors of 35 months (12-84) OS and PFS rates were 70% and 53% at 1 year (95% CI 58-79, 41-64) and 50% and 30% at 3 years, respectively (38-62, 19-41). The cumulative incidences of relapse were 25% and 47% at 1 and 3 years, respectively (16-35, 35-58), and 1 year NRM was 22% (13-32). Deaths were balanced between relapse and non-relapse causes (54% and 46% respectively). Incidence of grade II-IV acute GVHD was 7% at 100 days (3-14), and of chronic GVHD was 8% at 1 year (3-16). In univariable analysis, intermediate-high risk ISS assessed prior pre-alloHCT salvage therapy was associated with lower OS (3 year 30 v 54%, p=0.037), lower PFS (3 year 9 v 33%, p=0.013), and greater relapse incidence (3 year 72 v 39%, p=0.004). Older age and GVHD prior to 6 months were also associated with lower OS; older age, more heavily pre-treated disease, and worse disease status at alloHCT were associated with lower PFS; and heavier pre-alloHCT treatment was also associated with higher relapse (Table 1). Higher HCTCI was not associated with increased NRM (1 year 22 v 16 v 27% for HCTCT 0, 1-2, ≥3 respectively; p = 0.863). Discussion We describe a cohort of high-risk heavily pretreated RRMM patients with durable OS (50% at 3 years), comparatively low PFS (30% at 3 years), and historically improved rates of NRM (22% at 1 year). We also importantly identified numerous pre-alloHCT variables that were associated with survival, PFS, and relapse. Amongst these, poor ISS measured prior to pre-alloHCT salvage was consistently associated with worse survival and relapse outcomes and may speak to this score's utility as a dynamic measure of disease risk in patients exposed to multiple lines and therapy. Conclusions Our report reinforces that CD34+ selected alloHCT can achieve prolonged disease control and long term survival in high risk, heavily treated refractory MM populations, and newly describes certain pre-transplant variables that may help identify patients with better potential survival and relapse outcomes. Given the dismal prognosis and lack of established alternate therapies for RRMM patients, we advocate that identification of favorable or adverse pre-transplant variables during pre-alloHCT assessment be used to inform alloHCT decision-making rather than to exclude certain patient cohorts from this potentially effective and curative treatment option. Disclosures Perales: Abbvie: Other: Personal fees; Merck: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Takeda: Other: Personal fees; Novartis: Other: Personal fees.

scholarly journals Multiple Myeloma in Adolescent and Young Adults: A SEER and CIBMTR Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Steven J Gibson ◽  
Jennifer A Thornton ◽  
Christin B DeStefano
Keyword(s):  
Multiple Myeloma ◽  
Young Adults ◽  
Medical Center ◽  
The United States ◽  
Marrow Transplant ◽  
Cell Transplant ◽  
Blood And Marrow Transplant ◽  
Race Ethnicity

Background Multiple myeloma (MM) is a disease of the elderly, with less than 3% of cases diagnosed in adolescents and young adults (AYA). Data on demographics, use of autologous stem cell transplant (ASCT), second primary malignancies (SPMs) and survival are scant to non-existent in the AYA MM population. To our knowledge, this study is the first to better understand characteristics and survival trends of this unique population. Methods The Surveillance, Epidemiology, and End Results (SEER)-18 and Center for International Blood and Marrow Transplant Research (CIBMTR) datasets were utilized. Inclusion criteria were patients younger than 40 years old diagnosed with MM (ICD-O code 9732/3) between 2000-2017 (SEER) and 2008-2018 (CIBMTR). Variables assessed included age (&lt;30 vs. 30-39), gender, income (&lt;65K vs. ≥65K), race/ethnicity, place of residence (metropolitan vs. non-metropolitan), and year diagnosed (2000-2005 vs. 2006-2011 vs. 2012-2017). Incident SPMs were characterized as standardized incidence ratios (SIR). Analyses were conducted with STATA and data were censored at time of death or loss to follow up. Kaplan-Meier curves were generated for myeloma-specific survival (MSS). Individual variables were compared via log rank tests and Cox proportional hazard regression models. Model fit was assessed with Akaike's information criterion and Snell residuals. Assumptions of the Cox proportional hazards model were evaluated with log-time. Results There were 1,087 and 1,142 patients meeting criteria in SEER and CIBMTR, respectively. Median MSS was 181 months (15 years). The most common causes of death were MM (76%), SPMs (5.5%), and infection (3.6%). Statistically significant incident SPMs were lung cancers (SIR 4.94, p&lt;0.05), non-Hodgkin lymphoma (NHL) (SIR 5.28, p&lt;0.05), and acute myeloid leukemia (AML) (SIR 14.62, p&lt;0.05). Year of diagnosis strongly influenced survival. Compared to those diagnosed in 2000-2005, there was a 36% reduction in the risk of death among those diagnosed 2006-2011 (HR 0.64, 95% CI 0.49-0.82, p=0.001), and a 61% reduction among those diagnosed 2012-2017 (HR 0.39, 95% CI 0.26-0.58, p&lt;0.001). Race/ethnicity, gender, and age did not impact MSS. Among the AYA MM patients who received ASCT, notably 26% had a hematopoietic cell transplant comorbidity index (HCT-CI) of ≥ 3, nearly all received melphalan conditioning, and 80% received ASCT within the first year of diagnosis. One and four-year post-ASCT survival were 96% and 81%, respectively. Discussion To our knowledge, this is the first study assessing MM trends in the AYA population. Despite AYAs being underrepresented in MM clinical trials, the dramatic improvement in survival over time reflects efficacy of new drug approvals in this young population. It is also interesting that racial and socioeconomic disparities which are pervasive in the older adult MM population were not demonstrated in AYAs. AYA patients died from SPMs at rates similar to the adult MM population (3-6%), and notable incident SPMs in the AYA population were lung cancer, NHL, and AML. Also noteworthy was the high number of AYA MM patients who underwent up-front ASCT, which was nearly the same number of patients from the SEER dataset over half the amount of time. Since AYA MM patients have been underrepresented in trials utilizing ASCT, a survival benefit of ASCT in this population has not been demonstrated in the era of novel therapies. Further, given possible underlying genetic predisposition in AYA MM patients, long-term post-ASCT follow up is needed to better understand long-term toxicities including risk of hematological SPMs. Disclosures The findings and opinions contained herein are those of the authors and do not represent the views/opinions of the United States Air Force, Walter Reed National Military Medical Center, David Grant Medical Center, Department of Defense, or the Center for International Blood and Marrow Transplant Research (CIBMTR). Disclosures No relevant conflicts of interest to declare.

scholarly journals Conditional Survival Analysis of 816 Multiple Myeloma (MM) Patients Constitutes a Different Way to Provide More Specifically Determined Prognosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2091-2091
Author(s):  
Maximilian Schinke ◽  
Inga Promny ◽  
Stefanie Hieke ◽  
Johannes M. Waldschmidt ◽  
Gabriele Ihorst ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Conditional Survival ◽  
Term Survival ◽  
Long Term Survival ◽  
Prediction Time ◽  
Risk Parameters ◽  
Over Time

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.

scholarly journals Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8096-8096 ◽  
Author(s):  
Geetika Srivastava ◽  
Vishal Rana ◽  
Martha Lacy ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Entire Cohort ◽  
Dexamethasone Therapy

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.

Follow up Analysis for MRC Myeloma VII Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 927-927
Author(s):  
Gareth J. Morgan ◽  
Faith E. Davies ◽  
Kim Hawkins ◽  
Susan E. Bell ◽  
Julia M. Brown ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapy Group ◽  
Intensive Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Conventional Dose

Abstract The results of the MRC Myeloma VII trial and overview analysis of comparable trials have suggested that VAD-like induction chemotherapy followed by high dose therapy (HDT) with autologous transplantation may be regarded as a new standard treatment for multiple myeloma. However, there is a need for data from the extended follow up of patients in such trials to provide confirmatory evidence of the benefit of treatment incorporating HDT compared with conventional dose treatment, in particular to determine the long term difference in survival and the impact of attaining a complete response (CR) following intensive treatment. We present an updated analysis of Myeloma VII with median follow up of 5.5 years. Myeloma VII is the largest trial of its type in which patients with previously untreated multiple myeloma, age <65 years, were randomized to receive either standard conventional-dose combination chemotherapy (ABCM) or a sequence of treatment, C-VAMP followed by high dose therapy (HDT), typically melphalan 200g/m2 with autologous stem cell transplant. The planned maintenance in both arms was interferon α-2a. The trial, initiated in 1993 and closed to entry in 2000 and was conducted to MRC guidelines for good clinical practice in clinical trials. In the 401 evaluable patients the CR rate was 44% in the intensive therapy group, 8% in the standard therapy group (p<0.001). Intention to treat analysis showed a survival benefit of 14.1 months in the intensive arm (Figure 1); median 56.3 months (95% CI 46.0–74.6) vs. 42.2 months (95% CI 33.1–48.9), p=0.004 (log rank test). Progression free survival was also improved in the intensive group, median 31.2 months (95% CI 27.1–37.5) compared with 19.5 months (95% CI 16.2–21.6) in the standard group (p=<0.001). This analysis provides confirmatory evidence that treatment including high dose therapy is superior to conventional dose chemotherapy. Long term follow up of this study shows that the benefits of intensive treatment are maintained long term and that an important therapeutic aim is the achievement of CR. For the patients receiving the full protocol, the differences are accentuated, implying that maximising numbers of patients getting to transplant is an important therapeutic aim. These results would also support the continuing development of peri-HDT strategies to further improve outcomes. Figure Figure

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