Long Term Follow-up of 121 Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukaemia (Ph+ALL) Treated in Prospective GMALL Trials Supports a Greater Emphasis On Allogeneic SCT as Definitive Postremission Therapy.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2608-2608 ◽  
Author(s):  
Heike Pfeifer ◽  
Christoph Wettner ◽  
Barbara Wassmann ◽  
Aristoteles A.N. Giagounidis ◽  
Matthias Stelljes ◽  
...  
Keyword(s):  
Elderly Patient ◽  
Elderly Patients ◽  
Research Funding ◽  
Intensive Chemotherapy ◽  
Front Line ◽  
Consolidation Chemotherapy ◽  
Line Therapy ◽  
Postremission Therapy

Abstract Abstract 2608 Background: Combined treatment with a tyrosine kinase inhibitor (TKI) and ALL-type induction and consolidation chemotherapy followed by allogeneic SCT is standard front-line therapy for younger patients with Ph+ALL, but the value of adding intensive chemotherapy to a TKI in elderly patients is controversial. More than 90% of elderly patients achieve a complete remission, irrespective of the type of TKI-based induction, but relapse is the major cause of treatment failure. In a previously reported randomized trial examining imatinib combined with intensive induction and consolidation chemotherapy for Ph+ALL in elderly patients (n=55), the probability of overall survival (OS) after 24 months was 42% ± 8% (Ottmann OG et al., Cancer. 2007; 109:2068-76). To date, very little published data on long-term outcome of elderly patients with Ph+ALL are available. Aims: We conducted the present analysis to determine whether subsets of patients derive long-term benefit from combined imatinib plus intensive chemoptherapy, examine the characteristics of long-term survivors, determine whether such patients can be identified by assessment of MRD, and obtain preliminary results on the feasibility and efficacy of SCT in this population of elderly patient. Study design and patients demographics: Our current analysis includes a total of 121 patients (119 ALL, 2 CML in lymphoid blast crisis), with a median age of 66 years (range 54–80). Fifty-five patients were enrolled in a previously reported randomized clinical trial comparing single-agent imatinib and chemotherapy as induction therapy, followed by up to 6 cycles of consolidation chemotherapy; a further 67 patients were subsequently treated according to this protocol as per recommendation by the GMALL Study Group. Results: The overall CR rate was 88%, median time to progression was 14.5 months (range 0.5–102) and OS was 18.6 months (range 0.5–102), respectively. Probabilities of remission duration, survival and TTP at 5 years were 19%, 22% and 19%, respectively. The type of initial induction therapy had no significant impact on OS and DFS. Of 113 pts, who were evaluable for comorbities, pulmonary disease was the only comorbidity associated with inferior outcome (median OS 13 months vs. 20 months, univariate analysis p=0.02). Allogeneic SCT was performed in CR1 in 12 patients and as salvage therapy in another 7 patients. Median age of these 19 patients was 62y (range 54–69). The time from diagnosis to SCT in CR1 was 4.6 months (2.9 mo – 16.8 mo) and from relapse to SCT in >CR1 3 months (2.1 mo – 6.1 mo). The 5yr OS in patients transplanted in CR1 vs. non-transplanted patients was superior (48% vs 22%). Remarkably, OS of the 7 patients transplanted beyond CR1 as part of salvage therapy was 43% after 4.5 years. With a median follow-up of 21.6 months (range 3.3– 54) after SCT, 8 patients are in ongoing CR with a median OS of 51.8 months from initial diagnosis (range 35 – 66), 5 pts. died in CR, 6 pts. relapsed. Conclusions: The combination of imatinib with intensive chemotherapy is feasible in elderly patients, but long-term survival is poor primarily due to high relapse rate. Allogeneic SCT in CR1 is superior to conventional therapy and should be considered as front-line therapy in this elderly patient population. The encouraging results of allogeneic SCT performed beyond CR1 suggest that SCT should be considered as definite postremission therapy in a larger proportion of elderly patients than is current practice. Disclosures: Ottmann: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

Imatinib and Interferon-Alpha Maintenance Therapy for Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Ineligible for Allogeneic Stem Cell Transplantation (SCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2042-2042
Author(s):  
Heike Pfeifer ◽  
Barbara Wassmann ◽  
Andreas Käbisch ◽  
Michael Lübbert ◽  
Lothar Leimer ◽  
...  
Keyword(s):  
Side Effects ◽  
Elderly Patients ◽  
Maintenance Therapy ◽  
Low Dose ◽  
Front Line ◽  
Consolidation Chemotherapy ◽  
Mutation Status ◽  
Line Therapy ◽  
Remission Duration

Abstract Abstract 2042 Poster Board II-19 Introduction: The tyrosine kinase inhibitor imatinib (IM), alone or in combination with chemotherapy, has become the mainstay of front-line treatment for Ph+ ALL. We recently demonstrated that IM in combination with intensive consolidation chemotherapy of approximately one year duration is feasible in elderly patients with de novo Ph+ ALL, but is associated with a high relapse rate. Allogeneic SCT (alloSCT) is potentially curative but may not be feasible in most elderly or comorbid patients. Maintenance therapy (MT) in such patients is conceptually attractive, but data on whether any type of MT facilitates long-term leukemia-free survival of patients with Ph+ALL in first CR is lacking. Based on data suggesting that interferon-alpha (IFN-a) possesses anti-leukemic activity in patients with Ph+ALL, we conducted a phase II study to determine the feasibility and efficacy of MT consisting of imatinib in combination with low-dose (LD) IFN-a in elderly patients with Ph+ALL who were not eligible for SCT. In addition, we examined whether bcr-abl transcript levels and mutation status were predictive of relapse and remission duration. Methods: Nineteen elderly patients (median age 66 yrs; [60-75 yrs.]) who had received IM-based remission induction and consolidation therapy as reported previously (Ottmann et al., Cancer 109:2068-76, 2007) were enrolled in a clinical trial of IM 400 mg daily in combination with LD-IFNa with a target dose of 3 Mio IU/week. At the time of enrollment, the majority of patients (n=12) had received five (n=3) or six (n=9) consolidation cycles, the remaining patients had discontinued intensive front-line therapy after four (n=2), three (n=1), two (n=1), and one (n=1) consolidation cycles, 2 patients were switched to MT after induction. The median number of cycles of consolidation chemotherapy given concurrently with IM was six. Minimal residual disease (MRD) was serially assessed by quantitative RT-PCR, mutational analyses was performed by D-HPLC and direct sequencing. Results: The median overall duration of MT is 26 mos. (range 3-92 mos.). Seven of 19 pts. (37 %) are in ongoing CR, with a median remission duration from start of maintenance of 76.7 mos. (54-91 mos.). Median overall survival of all pts. is 61 mos. (range: 20-99 mos.). Eleven of 18 evaluable pts. experienced side effects which lead to a dose reduction of IFN. 9 pts. suffered from moderate depressions or fatigue. Hematologic toxicity was mild: only 2 pts. developed grade 3 cytopenia during MT. Remission duration was independent of the number of previous cycles of intensive chemotherapy, of the MRD response during the first 6 mos. of intensive front-line therapy (16 mos. vs. 26 mos.) and of achievement of PCR negativity at any time during intial therapy. Surprisingly, the bcr-abl transcript level at the start of MT likewise had no impact on time to disease recurrence. Conclusions: In elderly Ph+ALL pts. ineligible for allogeneic SCT, maintenance with imatinib in combination with low-dose IFN-a results in long-term sustained remissions in a substantial proportion of patients, with acceptable side effects. Surprisingly, the MRD response and mutation status prior to MT were not significantly predictive of remission duration. Likewise, greater intensity of prior chemotherapy as determined by the number of administered consolidation cycles had no significant benefit with respect to remission duration during MT. More extensive evaluation of tyrosine kinase inhibitors in combination with LD IFNa as MT for Ph+ALL is warrented. Disclosures: Ottmann: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria.

Imatinib (IM) and Interferon-Alpha (IFN-a) Maintenance Therapy Is Associated with Long-Term DFS in a Subset of Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ALL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1503-1503 ◽  
Author(s):  
Heike Pfeifer ◽  
Sylvia Wystub ◽  
A. Binckebanck ◽  
Barbara Wassmann ◽  
Andreas Käbisch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Elderly Patients ◽  
Research Funding ◽  
Low Dose ◽  
Hematologic Toxicity ◽  
Front Line ◽  
Cns Involvement ◽  
Line Therapy ◽  
Remission Duration

Abstract Abstract 1503 Background: The frequent development of acquired resistance in patients with Ph+ALL initially responsive to tyrosine kinase inhibitor(TKI)-based regimens highlights the need for more effective post-remission therapy. Imatinib or dasatinib as single agents or combined with chemotherapy are commonly employed, but do not adequately prevent relapse. Interferon-alpha as treatment for bcr-abl positive leukemias has attracted renewed interest, fueled by preclinical observations suggesting that IFN-a may target leukemic stem cells. Proposed mechansims of IFN-a action include recruitment of dormant CML stem cells into the cell cycle, enhancing their susceptibility to eradication by TKIs. Whereas several recent randomized clinical studies in CML demonstrate greater efficacy of combined IFN-a and TKI compared to TKIs alone, no long-term clinical data on the combination of IFN-a and TKIs are available for patients with Ph+ALL. Aims: This prospective, open-label phase II study was designed to investigate the combination of low-dose IFN-a with imatinib mesylate (IM) 600mg daily as maintenance therapy in Ph+ALL patients in terms of hematologic and non-hematologic toxicity and the ability to adhere to the planned dose of the study drugs. In addition, we examined whether bcr-abl transcript levels and mutation status were predictive of relapse and remission duration. Outcome with study treatment is compared with that of patients with Ph+ALL who received the same initial therapy, followed by maintenance with imatinib alone. Patients and study design: Patients with Ph+ALL in first CR after receiving induction and consolidation chemotherapy according the GMALL protocol for elderly Ph+ALL who were not candidates for allogeneic stem cell transplantation (SCT). were eligible. MT consisted of IM at a single dose of 600 mg daily, combined with low dose subcutaneous interferon-alfa-2a (RoferonÒ) starting at 1 MU three times a week with dose escalation to a target dose of 3 MU three times a week as rapidly as tolerated. The trial was approved by the Ethics Committee of the University of Frankfurt, Germany. Results: 19 elderly patients (median age 66 yrs; [60 – 75 yrs]) were enrolled in the combination study, 12 patients (median age 67 yrs; [58 – 75 yrs]) who received only IM as recommended MT after the same front-line therapy served as a control group. The median overall duration of MT is 26 mos. [3 – 110 mos]. Median overall survival for pts. receiving IM+ IFN-a is 5.4 yrs [2.5 – 11.4 yrs] vs. 2.9 yrs. [0.7 – 8.7 yrs] for pts. receiving IM alone (p=ns). For pts. receiving IM+ IFN-a, the median remission duration from start of maintenance is 2.2 yrs. [0.4–9.5 yrs] versus 0.75 yrs[0.1–7.6 yrs]. for patients receiving IM as MT (p=0.07). Three of 19 pts. are in ongoing CR 7.9, 8.6, and 10.4 years after start of maintenance. 4 pts. died in CR of causes unrelated to leukemia and 12 patients relapsed, 2 (16%) with isolated CNS involvement. Remission duration was independent of the number of previous cycles of intensive chemotherapy, of the MRD response during the first 6 mos. of intensive front-line therapy (16 mos. vs. 26 mos.) and of achievement of PCR negativity at any time during intial therapy. Surprisingly, the BCR-ABL transcript level at the start of MT likewise had no impact on time to disease recurrence. Prolonged MRD positivity without hematologic relapse occured in several patients. For pts. receiving IM as MT, 2 of 12 pts. are in ongoing CR 6.5 and 7.6 yrs. from start of maintenance. 2 of the 10 patients relapsed on MT with CNS involvement. Overall tolerability was acceptable, adverse events which lead to dose reductions for IFN-a were noted in 9 of 18 evaluable pts. Nine pts. suffered from moderate depression or fatigue. Hematologic toxicity during MT with IM+ IFN-a was mild with grade III cytopenia developing in only 2 pts. Conclusions: In elderly Ph+ALL pts. ineligible for allogeneic SCT, maintenance with IM in combination with low-dose IFN-a results in long-term sustained remissions in a substantial proportion of patients, with acceptable side effects. Surprisingly, the level of MRD was not predictive for remission duration. The lack of relationship between number of consolidation cycles and remission duration suggests IM+IFN-a MT may be effective even if started earlier during front-line therapy. Evaluation of the more potent 2nd generation TKI in combination with LD IFN-a as MT for Ph+ALL is warrented. Disclosures: Ottmann: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

Follow-up Analysis of a Randomized Comparison of Prolonged Myelosuppressive Maintenance Therapy Versus Intensive Consolidation Therapy as Postremission Therapy in AML.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1056-1056
Author(s):  
Utz O. Krug ◽  
Maria Cristina Sauerland ◽  
Bernhard J Woermann ◽  
Wolfgang Berdel ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Postremission Therapy ◽  
To Receive

Abstract Abstract 1056 Poster Board I-78 Introduction: We previously showed that a prolonged myelosuppressive maintenance chemotherapy was superior to S-HAM as a postremission therapy in patients > 16 years of age with AML after a TAD-HAM double induction therapy and TAD consolidation chemotherapy with regard to relapse-free survival (RFS) and borderline significance of the overall survival (OS) in responding patients (Buchner et al., JCO 2003, 21:4496-4504). Here we present long-term follow-up data with a median follow-up of 7.9 years from diagnosis and 7.1 years from the date of complete remission. Patients and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were upfront randomized in the AMLCG1992 study of the German AML Co-operative Group to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age ≥ 60 years] x 6 (HAM in patients ≥ 60 years only in case of blast persistence on day 16 of therapy) induction, TAD consolidation, and monthly maintenance with cycles of cytarabine combined with either daunorubicin (course 1), 6-thioguanine (course 2), cyclophosphamide (course 3), and again 6-thioguanine (course 4), and restarting with course 1 for 3 years, or to receive TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age ≥ 60 years) x 8 instead of maintenance. Results: A total of 576 patients (69.2%) achieved a complete remission (CR) those were 294 of 429 (68.5%) patients randomized to receive maintenance and 282 of 403 (70.0%) patients randomized to receive intensive consolidation S-HAM (p=n.s.). 190 patients received maintenance therapy as intended and 135 patients received an intensive consolidation therapy as intended. This prolonged follow-up analysis verified the superior relapse-free survival in all patients in the maintenance arm (10-year RFS 30.0 ± 5.6 versus 19.9 ± 6.1 %, p = 0.015). Stratified by age, the 10-year RFS was superior in younger patients < 60 years (36.9 ± 7.1 versus 25.2 ± 8.0 %, p = 0.038) and borderline significant in elderly patients (17.2 ± 4.5 versus 6.8 ± 6.2 %, p = 0.075). A subgroup analysis of known risk groups (lactate dehydrogenase (LDH) level < 700U/l versus ≥ 700U/l at diagnosis, cytogenetic risk profile, bone marrow blasts on day 16 after the start of the induction therapy) revealed a superior RFS in the subgroup of patients with LDH level > 700 U/l at diagnosis (33.5 ± 12.3 versus 18.2 ± 9.5 %, p = 0.043). This superior RFS also translated into a superior 10-year relapse-free interval (RFI) of all responding patients in the maintenance arm (35.7 ± 6.3 versus 27.6 ± 5.9 %, p = 0.015) with borderline significance in younger patients (42.9 ± 7.4 versus 35.0 ± 7.4 %, p = 0.053) and a significant difference in elderly patients (20.6 ± 10.0 versus 8.4 ± 7.5 %, p = 0.043). In this updated analysis, there was a trend, but no significant difference in the OS (maintenance arm: 10-year OS 24.3 ± 4.8, intensive consolidation arm: 19.7 ± 4.7 %, p = 0.148), and we verified a trend for a better OS in responding patients for the maintenance arm (10-year OS in responding patients 33.6 ± 7.5 versus 28.5 ± 6.2 %, p = 0.093). The event-free survival (EFS) also showed a trend towards better EFS in the maintenance arm (10-year EFS 20.7 ± 4.2 versus 14.8 ± 4.1 %, p = 0.082) which was significant in elderly patients (10-year EFS 10.5 ± 5.5 versus 3.9 ± 3.7 %, p = 0.044). Discussion: This updated analysis with a long-term follow-up of median 7.9 years from diagnosis and 7.1 years from CR verified the superior RFS and the trend for enhanced OS in responding patients. These results suggest the superiority of a prolonged monthly myelosuppressive maintenance therapy as compared to intensive consolidation S-HAM after TAD-HAM induction and TAD consolidation. Disclosures: No relevant conflicts of interest to declare.

Long-Term Outcome Of 151 Patients With Relapsed APL Receiving Second-Line With Chemotherapy Or Arsenic Trioxide-Based Regimens

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3922-3922
Author(s):  
Pau Montesinos ◽  
David Martínez-Cuadrón ◽  
Concha Rivas ◽  
Salut Brunet ◽  
José David González-San Miguel ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Salvage Therapy ◽  
Second Line ◽  
Front Line ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Chemotherapy Group ◽  
Line Therapy

Abstract Introduction Arsenic trioxide (ATO) is currently regarded as the best treatment option in relapsed acute promyelocytic leukemia (APL). The long-term outcome of salvage therapy using an ATO-based approach compared with chemotherapy based regimens is not well established. We analyze the clinical outcome of 151 APL patients relapsing after front-line therapy with ATRA and anthracycline, who received second-line therapy with chemotherapy or ATO-based regimens. Methods From June 1997 to May 2013, 151 patients (94 M/57 F; median age: 42 years, 2-81) relapsed after front-line therapy with PETHEMA trials. Patients presented with either molecular relapse (n=47) or hematological relapse (n=104). Sixty-seven patients (44%) followed salvage therapy with chemotherapy-based regimens (chemotherapy group) consisting of induction with mitoxantrone plus cytarabine plus ATRA (n=45), EMA (n=7), or other regimens (n=15). Patients not eligible for stem-cell transplantation (SCT) received consolidation with or without maintenance therapy. From October 2003, 84 patients (56%) received salvage therapy with ATO-based regimens (ATO group), comprising induction with ATO (0.15 mg/kg intravenously until CR, with ATRA [n=19] or chemotherapy [n=6]) followed by one consolidation cycle with ATO plus ATRA. If the post-consolidation bone marrow PCR was negative an autologous (auto)-SCT was recommended, when the PCR was still positive an allogeneic (allo)-SCT was planned. Patients not eligible for SCT received maintenance therapy with ATO plus ATRA with or without low-dose chemotherapy. Results Baseline characteristics, including sex, relapse-risk at primary diagnosis, morphologic and BCR subtype, as well as age at relapse and type of relapse, were similar in both cohorts of patients. Although not significant, patients rescued in the chemotherapy group presented earlier relapses (<18 months after initial APL diagnosis) (55% vs. 43%, P=0.13). CR rates were 85% in the chemotherapy group (8 deaths and 2 resistances) and 92% in the ATO group (4 deaths and 3 resistances) (P=0.11). In patients achieving second CR, a molecular CR was achieved after consolidation in 78% and 84%, respectively (P=0.38). Twenty-two patients in the chemotherapy group (39%) and 16 in the ATO group (21%) were not transplanted in second CR (P=0.04). The reasons for not SCT in the chemotherapy and in the ATO group were ineligibility for SCT (6 vs. 8 patients), early relapse before planned SCT (10 vs. 7 patients), and mobilization failure (6 vs. 1 patients). Overall, 34 patients underwent SCT in the chemotherapy group (auto-SCT, 20; allo-SCT, 14), and 57 underwent SCT in the ATO group (auto-SCT, 47; allo-SCT, 10). The median follow-up in the chemotherapy group was 95 months (range, 24-167), and 33 months (range, 3-100) in the ATO group. The 5-year overall survival (OS), disease-free (DFS), and relapse-free survival (RFS) in the chemotherapy group and in the ATO group were 40% vs. 56% (P=0.01), 31% vs. 39% (P=0.07), and 34% vs. 48% (P=0.09), respectively. For patients not receiving SCT because of mobilization failure or ineligibility, the 5-year OS, DFS, and RFS in the chemotherapy group and in the ATO group were 56% vs. 19% (P=0.11), 42% vs. 19% (P=0.49), and 42% vs. 29% (P=0.63), respectively. For patients receiving auto-SCT, the 5-year OS, DFS, and RFS in the chemotherapy group and in the ATO group were 55% vs. 80% (P=0.04), 40% vs. 54% (P=0.06), and 44% vs. 57% (P=0.13), respectively. For patients receiving allo-SCT, the 5-year OS, DFS, and RFS in the chemotherapy group (P=0.48), and 31% vs. 57% (P=0.34), respectively. All but one patient underwent auto-SCT with negative PCR (this patient relapsed rapidly after auto-SCT). Regarding allo-SCT, 7 patients were PCR+ and 17 were PCR negative before SCT (5-year DFS 0% vs. 41%, respectively, P=0.01). Conclusions This study performed in a large series with prolonged follow-up of APL patients relapsing after upfront therapy with ATRA and anthracycline shows high rates of CR either with ATO (92%) or chemotherapy regimens (85%). Salvage therapy with ATO-based regimen allowed performing more frequently auto-SCT with negative PCR, and this strategy resulted in an overall improvement of the 5-year OS, DFS, and RFS. Disclosures: No relevant conflicts of interest to declare.

Treatment Patterns and Outcomes of DLBCL after Failure of Front-Line Immunochemotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2683-2683 ◽  
Author(s):  
Umar Farooq ◽  
Matthew J Maurer ◽  
Stephen M Ansell ◽  
Tasha Lin ◽  
Grzegorz S. Nowakowski ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treatment Patterns ◽  
Front Line ◽  
Factors Associated ◽  
Line Therapy ◽  
First Relapse

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is curable for the majority of patients treated with anthracycline based immunochemotherapy (IC). However, up to 40% of patients will relapse or require retreatment of DLBCL and outcomes are poor in this setting. Here we examine the incidence, treatment patterns and outcomes of relapsed DLBCL in the R-CHOP era. Methods: Patients were prospectively enrolled in the University of Iowa / Mayo Clinic SPORE Molecular Epidemiology Resource (MER) within 9 months of diagnosis and followed for relapse, retreatment, and death. Clinical management at diagnosis and subsequent therapies were per treating physician. This analysis includes patients with DLBCL or primary mediastinal B-cell lymphoma (PMBCL) who underwent front-line anthracycline based IC; patients with primary CNS lymphoma or PTLD were excluded. All relapse and re-treatments were verified by medical record review. Response to front-line therapy was retrospectively classified per 2007 Revised Response Criteria for Malignant Lymphoma from available clinical and radiology records. Unplanned consolidative radiation (RT) without biopsy proven disease after achieving PR from IC (N=21) was not classified as a relapse. Results: 1039 patients with newly diagnosed DLBCL or PMBCL and treated with IC were enrolled in the MER from 2002-2012. Median age at diagnosis was 62 years (range 18-92) and 577 patients (56%) were male. 647 patients (63%) had stage III/IV disease and IPI at diagnosis was 0-1 in 350 patients (34%), 2 in 305 patients (29%), 3 in 250 patients (24%) and 4-5 in 134 patients (13%). At a median follow-up of 59 months (range 1-148), 258 patients had relapse or retreatment of DLBCL of which 184 (71%) died. Incidence of relapse was 21.7% (95% CI: 19.3%-24.4%) at 2 years and 25.5% (95% CI: 22.9%-28.5%) at 5 years. In addition, the incidence of lymphoma related death without documented relapse or retreatment was 4.7% (95% CI: 3.6%-6.2%) at 2 years. At first relapse, 174 patients (67% of relapsed) received platinum based salvage therapy with 90 (52%) subsequently proceeding to autologous stem cell transplant (ASCT). 22 patients received CNS directed systemic therapy at relapse with 9 (41%) proceeding to transplant, and 43 received non-platinum-based salvage systemic therapy with 7 proceeding to transplant (17%), 15 patients received RT only as 2nd line therapy, and 4 were untreated. At a median follow-up of 56 months (range 6-121) post-transplant, 39 of 107 patients who underwent transplant remain in remission with a 2-year post-transplant progression-free survival of 45% (95% CI 37%-56%). Response to front-line IC was predictive of post-relapse outcome. Survival post-relapse was superior in the 162 patients with responsive disease (CR or PR) at the end of front-line IC (median OS 21.0 months) compared to the 88 patients who had stable or progressive disease (median OS 6.8 months, HR = 2.33, 95% CI: 1.73-3.14 p<0.0001). Transient response in midst of front-line IC was similar to no response. Patients achieving a CR or PR to front-line IC were more likely to proceed to ASCT at relapse (55%) compared to patients with either SD or PD at the end of front-line IC (25% and 17% respectively, p<0.0001). Other factors associated with poor survival at first relapse were relapse within 12 months of diagnosis (HR = 2.24, 95% CI: 1.57-3.18, p<0.0001), IPI at diagnosis of 3-5 (HR=1.51, 95% CI: 1.13-2.03, p=0.0058), and age > 60 (HR =1.51, 95% CI: 1.12-2.03, p=0.0064). There was no difference in survival at first relapse by cell of origin (HR = 1.13, 95% CI: 0.74-1.72, p=0.59). Conclusions: Most patients undergo therapy after relapsed/refractory DLBCL but only one-third receive ASCT. Outcomes following all treatments for relapsed/refractory DLBCL remain poor. Factors associated with adverse outcomes include refractory to front-line therapy, early relapse, baseline IPI and advanced age. These outcomes provide relevant historical control for the many novel agents being tested in this unmet need. Figure 1. Figure 1. Disclosures Farooq: Kite Pharma: Research Funding. Maurer:Kite Pharma: Research Funding. Cerhan:Kite Pharma: Research Funding. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Thompson:Kite Pharma: Research Funding.

Long-term follow-up of brentuximab vedotin ± dacarbazine as first line therapy in elderly patients with Hodgkin lymphoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 7542-7542 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Andres Forero-Torres ◽  
Beata Holkova ◽  
Jerome H. Goldschmidt ◽  
Ralph V. Boccia ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Long Term Follow Up

Abstract WP27: Endovascular Treatment in Elderly Patient. Should We Continue Treating Them?

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Pedro Cardona ◽  
Blanca Lara ◽  
Helena Quesada ◽  
Nuria Cayuela ◽  
Lucia Aja ◽  
...  
Keyword(s):  
Elderly Patient ◽  
Elderly Patients ◽  
Endovascular Treatment ◽  
Successful Aging ◽  
Functional Independence ◽  
Long Term Results ◽  
Lower Percentage ◽  
Long Term Follow Up

Background: Endovascular treatment has been approved and has demonstrated effective in treating strokes with large vessel occlusion in trials published. A short number of elderly patients were included in these trials of thrombectomy. Current criteria admit patients without limit age but demand good baseline Rankin. However, despite those efforts in subgroup of older patients, we could achieve outcomes and long-term results different after endovascular treatment. Methods: We performed an analysis of consecutives patients treated with stent-retriever from March 2010 to May 2016. We dichotomize between younger (<80 years old) and elderly (>=80y) patients. We assessed good functional outcome in Rankin scale (0-2) at 3 month and long-term follow-up, percentage of successful recanalization (TICI 2b-3), symptomatic intracranial hemorrhage (SICH) and mortality. Moreover we determine percentage of futile recanalization in elderly patients and variables associated to failed thrombectomy. Results: A total of 622 patients were analyzed, mean age 67+/-12, baseline NIH:17, OSTP (onset stroke time to groin puncture): 279 min, baseline Rankin 0-1: 92%. Subgroup of elderly patients represented 21% of patients (131pt): mean age 83 (80-92), NIH:18, OSTP: 272 min, baseline Rankin 0-1:96%. We compare percentage of successful recanalization (TICI 2b-3) between younger and older patient (75% vs 60%; p:0.001). In multivariate analysis functional independence at 3 month (mRs 0-2) was significantly worse in elderly subgroup compared with younger patients (23% vs 51% ) and mortality (25% vs 17%). In a subgroup of long-term follow-up we found in elderly patient an increase of mortality (49%) after 2.5 years and lower percentage mRS 0-2 (18%), due to morbidity and fragility after stroke. Futile recanalization was higher in elderly patients compared with younger (31% vs 17%). Variables associated to futile recanalization in this subgroup of patients were ASPECTS<8 and hostile vascular access to occluded artery. Conclusions: We recommend more restrictive criteria to endovascular treatments in elderly patients. A low percentage of good outcome and high percentage of mortality at long-term follow-up don’t contribute to recent health target of successful aging.

Azacytidine in Refractory or Relapsed AML After Intensive Chemotherapy (IC): Results of the French ATU Program.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1054-1054 ◽  
Author(s):  
Raphael Itzykson ◽  
Sylvain Thépot ◽  
Christian Recher ◽  
Jacques Delaunay ◽  
Bruno Quesnel ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Research Funding ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Disease Status ◽  
High Risk Population ◽  
Intensive Chemotherapy ◽  
First Relapse ◽  
Refractory Aml

Abstract Abstract 1054 Poster Board I-76 Background: Limited options are available in AML refractory to or relapsing after intensive chemotherapy (IC), especially in elderly patients (pts). Azacytidine (AZA) prolongs survival when used as first line treatment of higher-risk MDS and WHO AML with 20-29% BM blasts (Lancet Oncol 2009). Its role in relapsed/refractory AML, especially with baseline BM blasts > 30%, has not been evaluated in large patient (pt) series. Methods: An AZA compassionate program (ATU) was opened in France between Dec 2004 and Dec 2008 for higher risk MDS, and for AML not candidates or refractory to IC. We retrospectively analyzed the outcome of WHO AML (including RAEB-t) included in this program in the 42 centers with complete pt reporting, and who had received ≥ 1 cycle of AZA after relapse or failure of IC. Results: 184 pts were included. Median age was 64 years, 58 pts had prior MDS, 14 had RAEBt at diagnosis, and 16 had therapy-related AML. Cytogenetics (MRC classification) was favorable (fav) in 2, intermediate (int) in 115 (including normal karyotype (NK) in 75), unfavorable (unfav) in 53, and failed in 14 pts. 65 pts had failed to achieve CR (51 after 1, and 14 after ≥2 courses of induction IC), 91 pts were in 1st relapse (median CR duration: 11 months), 28 were in 2nd or subsequent relapse. 20 pts previously had received alloSCT (14 in 1st CR, 5 in 2d CR, 1 refractory). Median follow-up was 15 months. The median number of AZA cycles was 3 (1-28) at FDA/EMEA-approved MDS schedule (75 mg/m2/d x7d/4 w) in 75% and less intensive (5d/4w, or <75 mg/m2/d) in 25% pts, with concomitant valproic acid (VPA) in 33%. Febrile neutropenia occurred in 67% pts, requiring hospitalization in 41%. Overall response rate (ORR) (Cheson et al. JCO 2003 criteria) was 11%: CR: 13 (7%), CRi: 5 (3%), PR: 1 (1%). 44 pts died before completing 4 cycles, and AZA was stopped before 4 cycles in another 52 pts (lack of response: n=43, severe infection: n=3, pt decision: n=5, allo SCT: n=1). The remaining 69 pts failed to achieve response after 4 cycles. In the 13 pts with CR, 6 (43%) were in persistent CR after a median follow-up of 7 months. In total, 9 pts received alloSCT after AZA: 2 CR, 7 refractory. Median OS was 7.8 months (1y OS: 29.1%). In univariate analysis, age, prior MDS, disease status (1st, ≥2nd relapse, refractory), WBC count at diagnosis, addition of VPA, and CR1 duration for pts in 1st relapse, did not influence ORR or OS. Only normal karyotype at onset of AZA improved ORR and OS (ORR: 18% vs 7%, p=0.04; 1y-OS: 44.4% vs 15.9%, p=0.001). We next restricted our analysis to the 141 pts with refractory AML (defined as failure of ≥2 IC cycles in pts <60y and ≥1 IC cycle in pts ≥60y) or in first relapse. 102 of them were aged ≥ 60y (median age 68y; 40 refractory, 62 in 1st relapse; median 1st CR duration: 12 months, range 2 - 54). Their ORR was 13% (CR 9%, CRi 4%). 1y OS was 29.4%, and median OS 8.9 months. OS was not influenced by previous MDS (n=32) or disease status (relapse/refractory). OS was improved in pts with NK (1y OS 42.5% vs 17.3%, p=0.02). The remaining 39 pts were aged < 60y (median age 52y); 10 of them were refractory, and 29 in first relapse (including 12 with unfav karyotype and 10 having failed 1 IC cycle after 1st relapse). Only 1 pt obtained CR and 1 PR (ORR: 6%), and median OS was 6.9 months (1y OS: 30%). Conclusion: In this high-risk population of relapsed/refractory AML, AZA resulted in significant responses and OS in AML pts refractory to one cycle of intensive chemotherapy (IC) or in untreated first relapse after IC, who were generally elderly pts. Results were more limited in pts with refractory disease after 2 induction cycles or first relapse resistant to one cycle of IC (who were generally younger). Those results warrant further studies of AZA in combination to other active agents in this population, particularly in elderly patients. Disclosures: Off Label Use: Azacytidine (FDA and EMEA approved in higher-risk MDS and RAEBt) used in WHO AML (including with marrow blasts > 30%). Fenaux:AMGEN: Research Funding; CELGENE: Research Funding.

Interest of the Association Azacitidine-Lenalidomide As Front Line Therapy in High-Risk Myelodysplasia (MDS) or Acute Myeloid Leukemia (AML) with Complex Karyotype

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5035-5035
Author(s):  
Elodie Scherman ◽  
Sandra Malak ◽  
Christine Perot ◽  
Norbert C. Gorin ◽  
Marie T Rubio ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Complex Karyotype ◽  
Front Line ◽  
Reduced Intensity Conditioning ◽  
First Line ◽  
Line Therapy ◽  
Acute Myeloid

Abstract Abstract 5035 Background. Results of intensive chemotherapy (ICT) in myelodysplasia (MDS) or secondary acute myeloid leukaemia (sAML) are poor, particularly in the presence of complex cytogenetic. Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only curative treatment but only a minority of patients is eligible for HSCT notably because of difficulties to assess disease control underlining the need for novel strategies. Although, the use of hypomethylating agents has improved the overall survival (OS) of MDS with excess of blasts and might be interesting in AML (Fenaux, Lancet Oncol 2009), the prognosis of high risk MDS and AML remains poor (Itzykson, Blood 2011). Lenalidomide has demonstrated its efficiency in MDS with del5q and, has also been tested in patients with high-risk MDS or AML (Ades, Blood 2009). Aim. We report our experience of the association of azacitidine and lenalidomide in patients presenting with high risk MDS or sAML and who were unfit for ICT. Patients and treatment. Eight consecutive patients were referred to our haematological department from August 2008 to March 2010 with a diagnosis of high-risk MDS or sAML because of the presence of a complex karyotype including in all cases abnormalities of the 5q chromosome. At diagnosis, median age of patients was 66.5 years (range, 23–76); median WBC was 2×10.9/L (range, 0.11–7.1) and median marrow blast was 23% (range, 11%-37%). Four patients had secondary therapy-related AML and four patients had type-2 refractory anemia with excess of blasts (RAEB). None of them was eligible for an intensive chemotherapy because of age and/or poor performans status and/or comorbidities. They received cycles of 28 days of azacitidine (75 mg/m2 Day 1 to 5 or 7 SC) and lenalidomide (10 mg per day, day 1 to 14 or 21, oral) as first line treatment for a median of 4.5 cycles (range, 1–13 cycles). Results. Main side effects were cytopenias: 7 patients on the 8 developed grade 4 thrombocytopenia. Five patients, 4 with baseline ANC more than 1000/mm3 developed grade 4 neutropenia. Severe infections occurred in neutropenic patients: 6 sepsis (4 fevers of unknown origin, 1 facial cellulitis, 1 fungal infection and 1 CMV reactivation.) including 2 septic shock. However, no death was related to the toxicity of the treatment. Of the eight patients, 6 achieved a haematological response (3 complete response (CR), 3 partial response (PR)) and 2 progressed under treatment. Among the 6 responding patients, initial responses occurred at a median of 10 weeks (range, 6–28 weeks) from the beginning of therapy. Two patients were allografted, one with a reduced intensity conditioning in haematological and cytogenetic CR at transplant, and the other one with a sequential type reduced intensity conditioning in complete haematological but partial cytogenetic remission at HSCT. With a median follow-up of 60 weeks for the responding patients, (range, 0–72), the 4 responding patients who were not allografted because of age did experience relapse at a median of 12 weeks (range, 8–36 weeks) from initial response while the two patients who were allografted are still alive in CR at 15 and 14 months after HSCT, respectively. Considering the whole population, with a median follow up of 18 months, the median OS was 15 months (range, 1–18 months), and median progression-free survival (PFS) was 9.5 months (range, 0–18 months). Conclusion. The association of azacitidine and lenalidomide in the context of high risk MDS and sAML might offer a significant probability of remission with tolerable toxicity. For patients considered for an allogeneic HSCT, the use in first line therapy of such novel combination strategy rather than intensive chemotherapy represents an interesting option particularly in the case of complex cytogenetic. Disclosures: Off Label Use: Interest of the association Azacitidine-Lenalidomide as front line therapy in high-risk myelodysplasia (MDS) or acute myeloid leukemia (AML) with complex karyotype.

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