Diffuse Pattern of Bone Marrow Involvement in MRI Is Associated with High Risk Cytogenetics and Poor Outcome in Newly Diagnosed, Symptomatic Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3920-3920
Author(s):  
Lia A Moulopoulos ◽  
Efstathios Kastritis ◽  
Evangelos Terpos ◽  
Maria Gkotzamanidou ◽  
Maria Roussou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Newly Diagnosed ◽  
Poor Survival ◽  
Normal Pattern ◽  
First Line ◽  
Agent Based ◽  
First Line Therapy ◽  
Line Therapy ◽  
Novel Agent

Abstract Abstract 3920 Magnetic Resonance Imaging (MRI) and specific recurrent cytogenetic abnormalities offer important prognostic information for multiple myeloma (MM) patients. However, limited data are available about the association between cytogenetic abnormalities and MRI patterns of marrow infiltration. To address this issue, we analyzed 203 newly-diagnosed, symptomatic patients who were treated in a single center, in Athens (Greece). The pattern of marrow involvement in MRI was recognized as: (1) normal when there was no evidence of abnormal signal; (2) focal which consisted of localized areas of abnormal marrow; (3) diffuse, in which the normal bone marrow is completely replaced; and (4) variegated which consists of innumerable small foci of disease on a background of intact marrow. Cytogenetic studies by FISH were performed in CD138 selected plasma cells using standard methodology. Eighty-six (42%) patients had focal pattern, 79 (39%) diffuse, 28 (14%) normal and 10 (5%) variegated pattern. Due to the low number of patients with variegated pattern and to our previous finding that variegated and diffuse patterns have similar outcomes, we analyzed these two patterns together. Patients with normal MRI pattern presented with better performance status (86% had ECOG PS ≤1 vs. 47% and 45% of patients with focal or diffuse patterns, p<0.001). Patients with focal or diffuse infiltration had features of advanced disease, such as anemia (Hb <10 g/dl; p<0.001), elevated serum LDH ≥300 IU/L (p=0.008) and advanced ISS stage (p<0.001). Patients with focal MRI pattern presented less often with renal impairment (eGFR <50 ml/min; p=0.017) but more often with lytic bone disease (p<0.001). The presence of del17p was more common in patients with diffuse pattern (22% vs. 10% in patients with focal and none in those with normal pattern, p=0.04). Similarly, add1q21 was more common in patients with diffuse pattern (37% vs. 13% and 15% for patients with focal or normal pattern; p=0.038). Del13q was observed also more frequent in diffuse pattern (48% vs. 28% and 24% for focal and normal pattern, p=0.056) while there were no significant differences in the frequency of t(4;14) and t(14;16) among patients with different MRI patterns. In general, 56% of patients with diffuse MRI pattern had high risk cytogenetics [any of del17p, add1q21, t(4;14) or t(14;16)] vs. 31% and 22% of patients with focal and normal patterns (p=0.012). Most patients (70%) received first line therapy based on novel agents (thalidomide, bortezomib or lenalidomide). Response to first line therapy was similar for patients with different MRI patterns (76%, 77.5% and 75% for focal, diffuse and normal pattern, respectively). However, patients who were treated upfront with conventional chemotherapy (CC) and had a diffuse MRI pattern had inferior response (46% vs. 79% and 83% for patients with focal and normal patterns, respectively, p=0.024). When patients were treated with novel agent-based frontline therapy, the response rates were similar among MRI patterns (89%, 74% and 73% for diffuse, focal and normal MRI patterns, respectively; p=NS). The median survival for patients with normal, focal and diffuse MRI patterns was 102, 57 and 37 months, respectively (p<0.001). The respective median survival for patients who were treated with CC was: not reached yet, 51 and 23.5 months (p<0.001) and in those who received novel agent-based regimens was 47 months for diffuse pattern vs. not reached for patients with focal or normal MRI pattern (p=0.05). When we adjusted for other clinical factors and for treatment type, then diffuse MRI pattern was independently associated with poor survival (HR: 3.018, p=0.024). Other factors that were independently associated with poor survival were age (>75 years; p<0.001), CC (p=0.001), ISS (p<0.001) and serum LDH ≥ 300 IU/L (p=0.05). When high risk cytogenetics were included in the multivariate model then only high risk cytogenetics (HR: 2, p=0.046), ISS stage (p=0.027) and serum LDH ≥300 IU/L were independently associated with poor survival. In conclusion, diffuse MRI pattern of bone marrow infiltration is associated with the presence of high risk cytogenetics, such as del17p and add1q21. The strong correlation of diffuse pattern with poor survival, even in the era of novel agents, suggests the need for more effective therapies for those patients and highlights the importance of the performance of baseline MRI in all patients with symptomatic disease. Disclosures: No relevant conflicts of interest to declare.

Efficacy, Tolerability and Cost Benefit of a 5-Day Azacitidine Regimen

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5034-5034
Author(s):  
Francesca Pierdomenico ◽  
Antonio Almeida
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Total Dose ◽  
Haematological Toxicity ◽  
Cost Effective ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 5034 Background: Azacitidine is a hypomethylating agent indicated for treatment of higher risk Myelodysplastic Syndromes (MDS). A recently published phase III trial demonstrated improved overall survival (OS) of MDS patients treated with Azacitidine compared to those receiving conventional care regimens, thus establishing this treatment option as first line therapy in those patients for whom bone marrow transplantation is not an option. Standard regime has been 75 mg /m2/day during 7 days; however several other treatment schedules have been explored that may have equal efficacy and tolerability though being more cost-effective. Aims: Evaluate the efficacy of Azacitidine regimen in terms of transfusion independence (TI), overall response (OR), AML transformation and tolerability in patients with higher risk MDS and AML with dysplasia. Methods: Higher risk (IPSS INT-2 and high risk) MDS patients were treated at a single institution with Azacitidine with a dosing regime of 500 mg/m2 every 4 weeks administered over 5 days. The total dose was adjusted so that entire vials were used. OR, including complete response (CR), haematological response (HR) and partial response (PR) and TI, defined according to the 2000 International Working Group Criteria (IWG), were assessed by blood and bone marrow examination. Treatment cycles were repeated until toxicity or disease progression. Results: A total of 38 patients were treated with Azacitidine between January 2007 and December 2010. Mean age was 68 years old (range 85–33) and male sex was predominant (M:F of 1.5) Fifteen patients had refractory anaemia with excess blasts, eleven had AML with dysplasia, five had chronic myelomonocytic leukaemia, tree had refractory cytopenias with multilineage dysplasia and four had acute erythroblastic leukemia. Most patients were high risk according to IPSS scoring (82%). Azacytidine was used as first line therapy in 32% and as second line in 61%. An average of 5 cycles (1–22) per patient were administered. The TI rate was of 45%, with average response duration of 6.5 months. OR rate was of 32% (9 CR, 1 HR and 2 PR). Twenty-two patients died during the follow-up period. Six patients progressed to AML: five of them had never shown any response to Azacitidine, while the other one had obtained TI. Median survival from diagnosis was of 22 months, while median survival from beginning of treatment was of 12 months. Tolerability was good, mainly grades I and II gastrointestinal and skin toxicity. Eleven patients (26%) had Grade III haematological toxicity and four (11%) suffered Grade IV haematological toxicity. The Azacitidine schedule using 500 mg/m2/4 weeks with the total dose adjusted across the 5 days in order to avoid wastage, instead of 75 mg/m2/day during 7 days, allowed for significant costs reductions. Conclusion: The efficacy of Azacitidine in achieving TI and prolonging survival in MDS is well recognized. In this study, Azacitidine improved quality of life and overall survival regardless of the quality of response. Treatment was well tolerated, with limited toxicity. Our results, though coming from a small group of patients, were comparable to what reported in the literature in terms of efficacy and tolerability, and we showed that it is cost effective to use our schedule regime. Disclosures: Almeida: Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau.

Efficacy and safety of aspacytarabine (BST-236) as a single-agent, first-line therapy for patients with acute myeloid leukemia unfit for standard chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7007-7007
Author(s):  
Jessica K. Altman ◽  
Jamie Koprivnikar ◽  
James K. McCloskey ◽  
Vamsi Kota ◽  
Olga Frankfurt ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
De Novo ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
Standard Chemotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
De Novo Aml

7007 Background: Aspacytarabine (BST-236) is a prodrug of cytarabine, the backbone of acute myeloid leukemia (AML) standard of care chemotherapy, associated with toxicity which precludes its administration in older patients and patients with comorbidities. Aspacytarabine is inactive in its intact prodrug form until cytarabine is gradually released at pharmacokinetics which decrease the systemic exposure to peak toxic cytarabine levels, resulting in reduced systemic toxicity and relative sparing of normal tissues, enabling therapy with high cytarabine doses to patients otherwise unfit to receive it. Methods: A phase 2b open-label, single-arm study to evaluate the efficacy and safety of aspacytarabine as a first-line single-agent therapy in newly-diagnosed AML patients unfit for standard chemotherapy (NCT03435848). Aspacytarabine is administrated at 4.5 g/m2/d (containing 3 g/m2/d cytarabine) in 1-2 induction and 1-3 consolidation courses, each consisting of 6 daily 1-hour infusions. Patients with secondary AML, prior hypomethylating agent (HMA) therapy, and therapy-related AML, are eligible. Results: To date, in the ongoing study, 46 newly-diagnosed AML patients unfit for standard chemotherapy (median age 75 years) were treated with aspacytarabine and completed 1-4 courses of 4.5 g/m2/d aspacytarabine, including 26 patients (63%) with de novo AML and 17 (37%) with secondary AML. Six patients (13%) were previously treated with HMA (median 12 courses). The baseline median bone marrow blasts was 52%, and 54% and 29% of patients had adverse or intermediate European LeukemiaNet (ELN) score, respectively. Twenty (43%) patients had ECOG 2. Aspacytarabine is safe and well-tolerated in repeated-course administration. Grade > 2 drug-related adverse events include mainly hematological events and infections. The 30-day mortality rate is 11%. Of 43 patients evaluable for efficacy analysis to date, 15 patients (35%) reached a complete remission (CR) following 1 (13 patients) or 2 (2 patients) induction courses, all with complete hematological recovery (median 27.5 days, range 22-39 days). The CR rates in de novo AML patients and patients with adverse ELN score are 46% and 33%, respectively. Of the 11 patients evaluable to date for minimal residual disease (MRD) flow cytometry test, 8 are MRD negative (73%). While aspacytarabine treatment consists of a limited number of courses, median duration of response and median overall survival for responders are not reached at 12 and 24 months, respectively (end of follow up). Updated results will be presented at the meeting. Conclusions: The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone. Clinical trial information: NCT03435848.

Mo1310 OVER-THE-SCOPE CLIP AS FIRST-LINE THERAPY IN THE MANAGEMENT OF HIGH RISK BLEEDING PEPTIC-ULCERS: A CASE-MATCH CONTROL STUDY

2019 ◽  
Vol 89 (6) ◽  
pp. AB484
Author(s):  
Carlos Robles-Medranda ◽  
Juan M. Alcívar-Vásquez ◽  
Roberto Oleas ◽  
Jorge Baquerizo-Burgos ◽  
Juan I. Olmos ◽  
...  
Keyword(s):  
High Risk ◽  
Peptic Ulcers ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Bleeding Peptic Ulcers ◽  
Over The Scope Clip ◽  
Control Study

First-Line Therapy with Donor Derived HCMV-Specific T Cells Reduce Persistent HCMV Infection after Allogenic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 727-727
Author(s):  
Xiangyu Zhao ◽  
Xuying Pei ◽  
Xiaojun Huang ◽  
Ying-Jun Chang ◽  
Lanping Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
High Risk ◽  
Hcmv Infection ◽  
Antiviral Agents ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Risk Patients ◽  
One Year

Abstract Background: Human cytomegalovirus (HCMV) infection, especially persistent HCMV infection, is an important cause of morbidity and mortality after allogenic stem cell transplantation (allo-SCT). Antiviral agents remain the mainstay of treatment and are recommend as the first-line therapy for HCMV. However, drugs are associated with significant toxicity, and their efficacy is limited in the absence of cell-mediated immunity. In recent years, adoptive immunotherapy with HCMV-specific T cells (CTLs) has been developed as an alternative option for HCMV, and data from previous studies have indicated that infusion of CTLs at early-stage of HCMV infection may have better benefits compared to salavage therapy. However, because CTLs remains time consuming and cost-intensive, so far there have no reports of first-line therapy with CTLs for HCMV infection, and the mechanisms driving the sustained antiviral immunity induced by adoptive T cells transfer remain undetermined. Our previous study had demonstrated that patients with acute graft-versus-host disease (aGVHD) were at high risk to develop persistent HCMV infection. Therefore, in the current study, we selected patients who developed aGVHD before HCMV reactivated and started CTLs generation in advance. This risk-stratified measure successfully selected patients who had high risk resisting to conventional anti-HCMV therapy , and spared low risk patients as well, making it feasible and financially viable to use CTLs as a first-line therapy. Aims: To provide robust support for the safety and efficacy of CTLs given as a first-line therapy for HCMV infection after allo-SCT, and gain some insight into the underlying mechanisms. Methods: Firstly, using humanized HCMV infected mice model, we explored where the adoptive transferred CTLs cells trafficked, evaluated the antiviral efficacy of CTLs and investigated the recovery of HCMV-specific immunity after T cell transfer. Secondly, we conducted a prospective clinical trial enrolled 35 allo-SCT patients who diagnosed with acute GVHD and had high risk developing persistent HCMV infection, intervened with antiviral agents combined with CTLs as first-line therapy and evaluated the long-term safety and durability of antiviral responses. As controls, we selected a cohort of 70 high-risk patients as well as another cohort of 70 low-risk patients who only received antiviral agents as first-line therapy without CTLs. We also evaluated the immune response after infusion and analyzed the association between immune recovery and HCMV clearance. Results: i) In humanized HCMV infection mice, adoptive infused CTLs had the ability to homing to organs, and effectively combated systemic HCMV infection by promoting the restoring of stem cell derived endogenous HCMV-specific immunity. ii) In clinical trial, first-line therapy with CTLs significantly reduced the rate (2.86% vs. 20.00%, P=0.018) and the cumulative incidence (HR=7.60, 95%CI=1.22-10.15, P=0.020) of persistent HCMV infection, and showed a lower one-year treatment related mortality (TRM) (HR=6.83, 95%CI=1.16-8.90, P=0.030) and a better one-year overall survival (OS) (HR=6.35, 95%CI=1.05-9.00, P=0.040) compared to high-risk control cohort. The cumulative incidence of persistent HCMV infection, one-year TRM and OS in CTL cohort were comparable to those in low-risk control cohort. Moreover, first-line therapy with CTLs promoted the quantitative and functional recovery of CTLs in patients, which was associated with HCMV clearance. Conclusion: In this study, we firstly demonstrated the safety and efficacy of CTLs administration as a first-line therapy for HCMV infection in humanized HCMV infection mice, and in a large clinical cohort study. The data provided robust support for the benefits of donor derived CTLs in treating HCMV infection as a first-line therapy, and suggested that infused CTLs might probably stimulate the recovery of donor derived HCMV-specific immunity. This trial was registered at www.clinicaltrials.gov as #NCT02985775. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Thalidomide Plus Dexamethasone for Untreated Newly Diagnosed Multiple Myeloma Patients and Deep Vein Thrombosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5093-5093 ◽  
Author(s):  
Victor H. Jiménez ◽  
Virginia J. Domínguez ◽  
Eduardo E. Reynoso
Keyword(s):  
Multiple Myeloma ◽  
Deep Vein Thrombosis ◽  
Oral Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis ◽  
First Line Therapy ◽  
Line Therapy ◽  
Deep Vein

Abstract Background The combination of thalidomide/dexamethasone (TD) induces remission in approximately 70% of previously untreated patients with low or intermediate tumor mass. TD appeared superior to previous programs because of the high response rate and reasonable survival and its low frequency of serious complications. The aim of our study was to assess the efficacy of thalidomide plus dexamethasone as first line therapy and the incidence of deep vein thrombosis. Material and methods Patients with newly diagnosed and symptomatic MM (untreated patients) were evaluated. We enrolled all patients who fulfilled entire criteria for multiple myeloma between January 1998 and December 2005. Patients were divided into 2 groups: thalidomide plus dexamethasone (TD) and VAD group. The present study is a prospective, descriptive, longitudinal and observational one. Thalidomide was prescribed in an oral dose of 100 mg qhs and increased by 50 mg every 7 days to a maximum dose of 300 mg, depending on side effects. Dexamethasone was given in an oral dose of 20 mg/m2 each morning after breakfast on days 1–4, 9–12 and 17–20, followed by 10 days without therapy prior to the next cycle. Treatment with the combination was continued for at least 6 months or until the earliest occurance of maximum plateau of myeloma protein reduction, autologous transplant-supported intensification or other treatments. VAD was given as an Out-patient regimen including: vincristine (0.4mg/day, continuous IV), doxorubicin (9mg/m2/day, continuous IV) and dexamethasone (40 mg/day PO) with a median of 6 courses. Citrate plasma was used to investigate coagulation and anticoagulation parameters. Results Sixty newly diagnosed multiple myeloma patients were included in the study, 35 (58%) male and 25 (42%) female, aged 45–85 (mean 63). Underlying diagnosis was IgG MM in 44 (73.3%), IgA in 12 (20%) and light chain disease in 4 (6.7%). Clinical characteristics were similar for both groups. According to Durie Salmon criteria patients were grouped into: IA (n6, 10%), IB (n3, 5%), IIA (n12, 20%), IIB (n6, 10%), IIIA (n19, 31.6%) and IIIB (n14, 23.4%). The frequency of response (CR, NCR/VGPR and PR) in the group of thalidomide and dexamethasone was 73% being higher than VAD (53%)p0.005. CR was observed in 5 patients treated with thalidomide/dexamethasone (16%). Thrombosis complications DVT was observed in 7 patients. DVT occurred in 4 patients treated with TD and 3 with VAD. From the last 40 patients, 5 presented APC-R and 3 of them developed DVT. A significant shorter time to DVT was observed in patients exposed to VAD chemotherapy (first 2 cycles p 0.007). Patients developing APC-R were tested for Factor V Leiden mutation resulting negative. After patients developed any response criteria were retested for acquired activated protein C resistance, all of them went back to normal. Finally we conclude TD is an effective, less toxic therapy in comparison with VAD as first line therapy and in order to reduce incidence of DVT effective prophylactic anticoagulation should be implemented in all controlled trials, at least during the first few cycles of treatment.

Salvage Therapies in Patients with High-Risk Relapse After Fludarabine, Cyclophosphamide, Rituximab (FCR) for Chronic Lymphocytic Leukemia: The French CLL Intergroup Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1796-1796
Author(s):  
Luc-Matthieu Fornecker ◽  
Therese Aurran-Schleinitz ◽  
Anne-Sophie Michallet ◽  
Bruno Cazin ◽  
Jehan Dupuis ◽  
...  
Keyword(s):  
High Risk ◽  
Second Line ◽  
Complex Karyotype ◽  
First Line ◽  
Second Line Therapy ◽  
High Risk Patients ◽  
First Line Therapy ◽  
Line Therapy ◽  
Ultra High Risk ◽  
Risk Patients

Abstract Abstract 1796 Introduction: FCR chemoimmunotherapy is recommended as first line therapy for fit cll patients. Since the 2007 EBMT guidelines based on the previously published trials using FCR, the definition of high risk CLL has evolved, to include biologic parameters (TP53 disruption by deletion/mutation, high b2-microglobulin level, IgVH unmutated, complex karyotype), refractoriness (progression during fluda-based regimen or within 6mo of completion), and also remission duration (high risk if PFS after FCR <24mo, ultra-high risk if TTNT <24–36mo with TP53 del/mut). However, few data are available regarding the characteristiscs, response rate and outcome of CLL patients treated in second line after FCR first line. Patients and methods: In this multicentric retrospective study, we collected data from 117 patients who relapsed after FCR first line therapy and received second-line therapy (according to NCI2008 guidelines). Results: At the time of initial FCR therapy: patients characteristics were as follows: Binet B/C 87.2%, unmutated IgVH 52.2%, del11q 25.6% (n=30/81 with FISH available), del17p 6.8% (n=8/87 with FISH available), bulk>5cm 22%, complex karyotype 21% (n=12/57 with karyotype available). FCR yielded 93% ORR, with 66% clinical CR, 27% PR, and 7% failed to respond. Median PFS and TTNT were 27mo and 32.5mo, respectively. At the time of relapse: patients characteristics were as follows: del11q 16.4% (n=19/65 with FISH available), del17p 19% (n=22/77), bulk>5cm 26%, complex karyotype 44% (n=24/54 with karyotype available). According to FCR remission duration, 11.1% of patients were considered as truly FCR-refractory, 47% had PFS<24mo, 34.2% had TTNT<24mo. TTNT<24mo after FCR was correlated to age>65y, del17p (20% vs 0%) and complex karyotype (38% vs11%), but not with gender, IgVH status, del11q, or bulk>5cm. Based on FCR-refractoriness, or TTNT<24mo and/or del17p, 53 patients were considered as ultra-high risk (45.3%). Various regimen were used for second-line treatment after FCR: R-bendamustine (n=47, 40.2%), alemtuzumab-based therapy (single agent or with chemo/dexa, n=22, 18.8%), R-CHOP (n=15, 12.8%), FCR (n=14, 12%), and other miscellaneous regimens (as follows: R-alkylator (n=6, 5.1%), R-DHAP (n=4, 3.4%), R-methylprednisolone (n=3, 2.6%), or investigational drugs (n=6, 5.1%)). Thus, 74.3% of patients received a second course including rituximab-based chemotherapy. Overall response rate was 78.4%, with 13.8% clinical CR, 64.6% PR, and 21.6% failure/stable disease. 14 pts (12%) underwent stem cell transplantations, 8 had maintenance therapy ongoing (ofatumumab, alemtuzumab, or lenalidomide). With regards to factors defining high-risk relapse, distribution of salvage therapies was as follows: As expected, a second course of FCR was seldom used in high-risk patients. Among ultra-high risk patients, 30.3% received R-benda, 11.3% Alem-based Rx, 32% R-CHOP and 18% the miscellaneous regimens described above. After second-line therapy, median PFS was 12 months, median TTNT was 14mo, and median OS was 36mo (20 deaths). On univariate analysis, complex karyotype (p=0.04) but not del17p (p=0.1), PFS<24mo (p=0.028) and TTNT<24mo (p=0.04) correlated with OS. Regarding treatment, OS was significantly improved in R-bendamustine-treated patients, as compared to alem-based or CHOP regimen (p=0.01). Most importantly, patients who received an allogeneic transplant benefited from significantly prolonged OS (at 4y, 70% vs 40%, p=0.03). Of note, only one patient treated with R-benda received allotransplant. Conclusions: This study shows that there are no consensus for second line therapy after FCR. Second line trials after FCR therapy are warranted. Definition of high-risk subsets of patients at relapse after FCR is of upmost importance in the management of CLL, to compare second-line strategies. Our data suggest that R-bendamustine is an efficient regimen even in high-risk patients (complex karyotype, PFS<24mo, TTNT<24mo). These data are important since this immunochemotherapy is now used as the backbone for combination with new compounds (ibrutinib, GS1101, GDC-199). Disclosures: Aurran-Schleinitz: Roche: Honoraria. Leblond:Roche: Advisory Board Other, Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen-Cilag: Honoraria.

Survival until First Progression and Post First Progression Survival Equally Contribute to the Overall Survival of Myeloma Patients: Differences in Patients ≤65 Years of Age Compared to Patients >65 Years

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4030-4030
Author(s):  
Efstathios Kastritis ◽  
Evangelos Terpos ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Dimitra Gika ◽  
...  
Keyword(s):  
High Risk ◽  
Renal Impairment ◽  
Initial Phase ◽  
Older Patients ◽  
Performance Status ◽  
Age Groups ◽  
First Line ◽  
Younger Patients ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 4030 Age is a major prognostic factor for the outcome of patients with multiple myeloma (MM), due to more intensive treatment in younger vs. older patients, comorbidities and toxicity, resulting in early discontinuation of treatment in older patients or even differences in disease characteristics. It is believed that the longer survival of patients ≤65 years is, to a large extent, due to the receipt of more lines of therapy and thus they can have an extended survival even after relapse to first line therapy. In order to decipher these differences in the outcome of MM patients of different ages, we analyzed 438 consecutive, unselected patients who were treated in a single center (Department of Clinical Therapeutics, University of Athens School of Medicine) from April 1994 to April 2012, and compared the characteristics and outcome of patients ≤65 years (166 patients), which are usually treated with more intensive therapies (including HDT), to that of patients 66–75 years (154 patients) and >75 years of age (118 patients). Some of these patients were included in clinical trials; however, even patients who were ineligible because of poor performance status, renal impairment or comorbidities were also included, thus, being more representative of the general myeloma population. Differences in the characteristics of patients of different age groups are depicted in the table. Younger patients presented less often with ISS-3, severe anemia, renal impairment or impaired PS than older patients. However, there was no difference in the detection of high risk cytogenetics. Response was higher and deeper in younger patients. Early deaths, within 2 months from initiation of therapy, occurred more often in older patients. Median PFS was longer in younger patients. Similar proportion of patients who relapsed have received 2nd line therapy (p=0.365). Post relapse survival (PRS) was 31 months for patients ≤65 years, 20 months for patients 66–75 years and 15 months for patients >75 years (p<0.001). The difference of PRS between patients 66–75 years and patients >75 years was also significant (p=0.004). Median OS was 71 months for patients <65 years, 46 months for patients 66–75 years and 31.5 months for patients >75 years (p<0.001). Thus, it seems that the OS of patients in each age group is distributed almost equally between the initial phase of the disease and post first relapse/progression (see Table). PFS <12 months was observed in 10% of patients ≤65 years vs. 22.5% and 29% of patients 66–75 and >75 years (p=0.003). PRS for patients with a PFS<12 months was 8 months for those ≤65 years, 10 months and 6 months for patients 66–75 and >75 years. Median OS was significantly better for patients who achieved CR or VGPR (58 months) vs. patients who achieved a PR (39 months) (p<0.001). For patients <65 years who achieved a CR/VGPR median OS has not been reached (4-year OS was 79%), for patients 66–75 years was 52 months and 40 months for those >75 years (p<0.001). Among patients with a minimum follow up ≥10 years (76 patients), 5 (6.5%) remained without progression for ≥10 years (4 of them had received HDT). In order to adjust for imbalances in baseline characteristics and depth of response (CR/VGPR vs. PR), we performed a multivariate analysis in which ISS stage (p<0.001), novel agent-based first line therapy (p=0.01), CR/VGPR (p=0.005) and age ≤65 (p<0.001), but not 66–75 vs. >75 years (p=0.092) were independently associated with improved survival. In conclusion, our data indicate that the survival of MM patients is distributed almost equally between the initial phase i.e. before relapse to first line therapy, and to subsequent phases of their disease i.e. post relapse survival. This is observed across all age groups, but in patients ≤65 years the duration of first response is significantly longer, perhaps due to more intensive therapies and to less frequent early deaths. In this unselected series of patients, the 10-year free of progression rate was 6.5%. Table ≤65 years 66–75 years >75 years p-value Males 60% 43.5% 51% 0.015 ISS-1 21% 18% 9% 0.02 ISS-2 50% 46% 47% ISS-3 29% 37% 45% Hb <10 g/dl 40% 45% 53% 0.075 eGFR <60 ml/min 29% 45% 55% <0.001 Performance status ≥2 39% 55% 59% 0.001 High risk cytogenetics (n=194) 50% 48% 41% 0.5 Upfront novel agents 73.5% 63% 81% 0.023 CR 34% 27% 17% 0.005 >VGPR 56% 49% 34% 0.001 ≥PR 81% 79% 64% 0.003 Early deaths 2% 6% 12% 0.005 Median PFS (months) 34 19.5 15 0.001 Median PRS (months) 31 20 15 <0.001 Median OS (months) 71 46 31.5 <0.001 Disclosures: No relevant conflicts of interest to declare.

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