Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

scholarly journals Long-Term Quality of Life after Pancreatic Surgery for Intraductal Papillary Mucinous Neoplasm

2021 ◽  
pp. 1-8
Author(s):  
Helwig Valentin Wundsam ◽  
Christiane Sophie Rösch ◽  
Patrick Kirchweger ◽  
Ines Fischer ◽  
Michael Weitzendorfer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Life Questionnaire ◽  
Ecog Performance Status ◽  
Long Term Follow Up ◽  
Eortc Qlq

<b><i>Introduction:</i></b> Intraductal papillary mucinous neoplasms (IPMNs) represent the most common precancerous cystic lesions of the pancreas. The aim of our study was to investigate if resection for non-invasive IPMNs alters quality of life (QoL) in a long-term follow-up. <b><i>Methods:</i></b> Patients (<i>n</i> = 50) included in the analysis were diagnosed and resected from 2010 to 2016. QoL was assessed at a median of 5.5 years after resection. At that point in time, the current QoL as well as the QoL before resection was evaluated retrospectively. The standardised European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Pancreatic Cancer (EORTC QLQ – PAN26) was applied for the QoL assessment. <b><i>Results:</i></b> After a median of 66 months postoperatively, the total QoL score significantly worsened (92.13 vs. 88.04, <i>p</i> = 0.020, maximum achievable score = 100) for patients (median age at surgery 68.0 years), mostly due to digestive symptoms. During the same follow-up period, median Eastern Cooperative Oncology Group (ECOG) performance status did not worsen (<i>p</i> = 0.003). <b><i>Conclusions:</i></b> Long-term QoL statistically significantly worsened after pancreatic resection for IPMN. The extent of worsening, however, was small, and QoL still remained excellent. Therefore, resection in cases of IPMN is appropriate, if indicated carefully.

Mature, real world progression-free survival (PFS) and overall survival (OS) milestones in stage IV, non-squamous, non-small cell lung cancer patients (nsqNSCLC) treated with first line pemetrexed(Pem)/platinum(Plat) followed by pem+/-bevacizumab(Bev) maintenance.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20721-e20721
Author(s):  
Parva Kiran Bhatt ◽  
Ibtihaj Fughhi ◽  
Sanjib Basu ◽  
Mary J. Fidler ◽  
Jeffrey Allen Borgia ◽  
...  
Keyword(s):  
Disease Control ◽  
Real World ◽  
Performance Status ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Prognostic Indicators ◽  
Ecog Performance Status ◽  
Neutrophil Lymphocyte Ratio

e20721 Background: Pemetrexed maintenance therapy is associated with superior survival in stage IV nsqNSCLC patients. We have observed long term disease control in some patients treated with at least one cycle of Pem/Plat with potential for maintenance pem. There are no reports of data regarding long term PFS and OS in patients treated with Pem regimens. The objectives of our retrospective analysis are to determine the frequency of long term disease control on Pem maintenance and to identify parameters associated with longer PFS/OS. Methods: We included all patients with Stage IV nsqNSCLC who received at least one cycle of pem/plat between May 2010 and Nov 2013. We identified 240 patients from our database and analyzed their demographics, lab values, dates of therapy, and dates of progression. PFS/OS was estimated by the Kaplan-Meier method and associations with patient characteristics were assessed by log-rank tests and Cox proportional hazards analysis. The shortest potential follow up was 5 years. Results: Median age was 66 years, 60% were female, and 72% were Caucasian. Baseline ECOG performance status was 0(22%), 1(50%) and ≥ 2(22%). Median PFS was 6.2 months. At 1, 2, 3, 4, and 5 years of follow up absence of disease progression was seen in 33%, 14%, 7.5%, 4%, and 3%, respectively. Additionally, in terms of OS at 1-5 years, we observed 54.5%, 35%, 21%, 14%, and 11%. Lower baseline neutrophil: lymphocyte ratio (NLR) was strongly associated with improved PFS when using NLR≤5 vs > 5 (median PFS 13.2 mo vs 5.6 mo) Additionally, baseline Hemoglobin (mean = 12.03 g/dL, HR = .904, p = .0046) and Albumin (mean 3.3 g/dL, HR = .7722, p = .024) were associated with better PFS. Conclusions: The similarity in median PFS in our patients (6.2 mo) and clinical trial data suggests that our group of real world patients did not have uniquely favorable baseline characteristics. However, the patients most likely to reach long PFS/OS milestones had favorable baseline prognostic indicators suggesting that this patient subset might also be most likely to benefit from the recently approved regimen which combined Pembrolizumab with Pemetrexed/Carboplatin.

Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9501-9501 ◽  
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo Dols ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Interim Analysis ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Randomized Study ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Ecog Performance Status

9501 Background: NIVO + IPI was shown to improve overall survival (OS) and durability of response vs chemo in 1L advanced NSCLC in CheckMate 227 Part 1, regardless of PD-L1 expression. We hypothesized that a limited course of chemo combined with NIVO + IPI could provide rapid disease control while building on the durable OS benefit seen with dual PD-1 and CTLA-4 inhibition. CheckMate 9LA (NCT03215706) is a phase 3 randomized study evaluating NIVO + IPI + 2 cycles chemo vs chemo in 1L stage IV/recurrent NSCLC. Methods: Adults with tx-naive, histologically confirmed stage IV/recurrent NSCLC, ECOG performance status 0–1, and no known sensitizing EGFR/ALK alterations were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles) (n = 361) or chemo (4 cycles) alone (n = 358), stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous). Chemo was based on histology. Pts with non-squamous NSCLC in the chemo-only arm could receive optional pemetrexed maintenance. Pts were treated with immunotherapy until disease progression, unacceptable toxicity, or for 2 y. The primary endpoint was OS; the interim analysis using Lan–DeMets alpha spending function with O’Brien–Fleming boundary was planned at ~80% information fraction (ie, after observing ~322 total events). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by blinded independent central review, and efficacy by PD-L1 subgroups. Exploratory endpoints included safety/tolerability. Results: Baseline characteristics were balanced across arms. At a preplanned interim analysis (minimum follow-up 8.1 mo), OS was significantly prolonged with NIVO + IPI + chemo vs chemo (HR 0.69, 96.71% CI: 0.55–0.87; P = 0.0006); statistically significant improvements in PFS and ORR were seen. With longer follow-up (minimum 12.7 mo), NIVO + IPI + chemo vs chemo continued to provide longer OS; median 15.6 vs 10.9 mo (HR 0.66, 95% CI: 0.55–0.80); 1-y OS rates were 63 vs 47%. Clinical benefit was consistent across all efficacy measures in key subgroups including by PD-L1 and histology. Grade 3–4 tx-related adverse events were reported in 47 vs 38% of pts in the NIVO + IPI + chemo vs chemo arms, respectively. Conclusions: CheckMate 9LA met its primary endpoint: a statistically significant improvement in OS was observed with NIVO + NSCLC-optimized IPI + a limited course of chemo vs chemo (4 cycles) in 1L advanced NSCLC. No new safety signals were reported. Clinical trial information: NCT03215706 .

Long-term real-world outcomes of first-line (1L) pembrolizumab (pembro) monotherapy in PD-L1 ≥50% metastatic NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21184-e21184
Author(s):  
Vamsidhar Velcheti ◽  
Xiaohan Hu ◽  
Bilal Piperdi ◽  
Lingfeng Yang ◽  
Thomas A. Burke
Keyword(s):  
Real World ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Metastatic Nsclc ◽  
The Us

e21184 Background: Pembro monotherapy was approved in the US in October 2016 as 1L therapy for patients with metastatic NSCLC and PD-L1 tumor proportion score (TPS) ≥50% based on findings from KEYNOTE-024. With 5-year follow-up in KEYNOTE-024, median overall survival (OS) was 26.3 months (95% CI, 18.3–40.4) in the pembro arm. With 4-year follow-up in KEYNOTE-042, median OS was 20.0 months (15.9–24.2) in the pembro PD-L1 ≥50% subgroup. Our aim was to describe long-term, real-world outcomes with 1L pembro monotherapy for patients treated at US oncology practices with disease characteristics similar to those in the KEYNOTE trials. Methods: Patients initiating 1L pembro monotherapy from December 1, 2016, through November 30, 2017, were selected from the US nationwide Flatiron Health de-identified, electronic health record-derived database if they had stage IV or recurrent metastatic NSCLC with PD-L1 TPS ≥50%, ECOG performance status 0–1, and no known EGFR/ALK/ROS1 aberration (confirmed negative EGFR/ALK for nonsquamous tumors). Enhanced manual chart review was used to determine real-world progression (rwP), tumor response (rwTR), and reasons for pembro discontinuation. OS and real-world progression-free survival (rwPFS) were estimated using the Kaplan-Meier method. Data cutoff was August 31, 2020. Results: Median study follow-up was 38.4 months (range, 33.1–44.9). Of 228 eligible patients, median age was 71 years (range, 46–82); 123 (54%) were women; 156 (68%), 12 (5%), and 60 (26%) had nonsquamous, not otherwise specified, and squamous NSCLC, respectively; and 209 (92%) were current/former smokers. History of brain metastasis was recorded for 17 (7%). Pembro was discontinued by 151 patients (66%), most commonly because of disease progression (70; 46%) and secondarily for toxic effect of therapy (35; 23%); 87 patients (38%) received ≥1 additional lines of therapy. OS, rwPFS, and rwTR results are shown below. Conclusions: In this real-world study with 3-year follow-up, patients with PD-L1 TPS ≥50% metastatic NSCLC without known EGFR/ALK aberrations and good performance status treated with 1L pembro monotherapy experienced median OS of 23 months, similar to the OS observed in phase III pivotal clinical trials, supporting the long-term OS benefits of 1L pembro monotherapy in this patient population.[Table: see text]

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1997 ◽  
Vol 15 (7) ◽  
pp. 2564-2569 ◽  
Author(s):  
S B Saxman ◽  
K J Propert ◽  
L H Einhorn ◽  
E D Crawford ◽  
I Tannock ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Intergroup Trial ◽  
Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

scholarly journals Survival of Critically Ill Oncologic Patients Requiring Invasive Ventilatory Support: A Prospective Comparative Cohort Study With Nononcologic Patients

2019 ◽  
pp. 1-8
Author(s):  
Rene López ◽  
Suraj Rajesh Samtani ◽  
Jose Miguel Montes ◽  
Rodrigo Perez ◽  
Maria Jose Martin ◽  
...  
Keyword(s):  
Critically Ill ◽  
Performance Status ◽  
Chronic Health Evaluation ◽  
Health Evaluation ◽  
Ecog Performance Status ◽  
Term Survival ◽  
Mechanically Ventilated ◽  
Oncologic Patients

PURPOSE Cancer is in the process of changing to become a chronic disease; therefore, an increasing number of oncologic patients (OPs) are being admitted to intensive care units (ICUs) for supportive care of disease or therapy-related complications. We compare the short- and long-term outcomes of critically ill mechanically ventilated OPs with those of their nononcologic counterparts. PATIENTS AND METHODS We performed a prospective study of patients admitted to our ICU between October 2017 and February 2019. Demographic, physiologic, laboratory, clinical, and treatment data were obtained. The primary outcome was survival at 28 days and at the end of the follow-up period. Secondary outcomes were survival according to acute severity scoring (Acute Physiology and Chronic Health Evaluation II score), Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson comorbidity index. RESULTS A total of 1,490 patients were admitted during the study period; 358 patients (24%) were OPs, and 100 of these OPs were supported with mechanical ventilation. Seventy-three percent of OPs had an ECOG performances status of 0 or 1, and 90% had solid tumors. Reason for admission to the ICU was postoperative admission in 44 patients and neutropenic infection in 10 patients. The follow-up period was 148 days (range, 42 to 363 days). Survival at 28 days was similar between OPs and nononcologic patients and associated with the Acute Physiology and Chronic Health Evaluation II score. However, long-term survival was lower in OPs compared with nononcologic patients (52% v 76%, respectively; P < .001) and associated with poor ECOG performance status. CONCLUSION Short-term survival of critically ill, mechanically ventilated OPs is similar to that of their nononcologic counterparts and is determined by the severity of the critical illness.

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.

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