scholarly journals The Impact of Age on the Outcome of Primary Treatment for Classical Hodgkin's Lymphoma: 70 Years of Age Is a Clinical Relevant Cutpoint and the Most Important Predictor of Overall Survival

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1559-1559
Author(s):  
Lourdes Calvente ◽  
Manjula Maganti ◽  
Mary Gospodarowicz ◽  
David C. Hodgson ◽  
Danielle Rodin ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Treatment Outcomes ◽  
Older Patients ◽  
Research Funding ◽  
Multivariable Analysis ◽  
Advanced Stage ◽  
Age Group ◽  
Grade 3 ◽  
The Impact

Introduction: Classical Hodgkin lymphoma (cHL) typically affects younger patients but 15-35% are >60 years. The age used to define an elderly population has varied but age 60 is frequently used. A clinically relevant definition of older age could be based on the use of alternate treatments due to different efficacy and/or toxicity. Treatment outcomes may also be influenced by tumor biology and patient comorbidity that vary with age. We evaluated the effect of age on treatment outcomes in cHL. Methods: All cHL patients treated at our centre between Jan 1999 and Dec 2015 were retrospectively analyzed. Clinical data were obtained from prospectively collected Lymphoma database and additional data was manually retrieved. Treatment for localized disease was combined modality (2-4 cycles of ABVD and potentially 6 cycles for bulk disease > 10 cm; radiation doses 20-35 Gy) with advanced disease typically receiving chemotherapy alone (ABVD 6-8 cycles). Older patients received individualized treatment. We used the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), (Sorror Blood 2005) as the elements can be abstracted retrospectively. Results: 607 patients were identified; 14% were >60 years and 6% were age >70. Baseline characteristics are outlined in table 1. Patients >70 presented more frequently with high-risk HCT-CI and worse ECOG PS. Patients > 60 presented more frequently with advanced stage (61-70 age group: 40%; >70 years: 46%). 65% of the patients age >70 presented with an IPS of >3. Chemotherapy alone approaches were used more commonly in older patients (age 61-70: 40%; age 70+: 51%) than in those <60 years (25%). Within the whole cohort 12 patients received non-anthracycline based treatment (<60: n=4; 61-70: n=1; and >70: n=7).For patients <60 and >70 this decision was made due to prior comorbidities that precluded the use of standard treatment, and for the patient in the 61-70 was because of acute toxicity with ABVD-based chemotherapy. Treatment was discontinued in 33% of the patients > 70 (77% due to toxicity), 21% in the 61-70 years group (30% toxicity) and 6% in patients <60 (29% toxicity). Patients > 70 had higher rates of grade 3-5 febrile neutropenia (28% versus 15% [age 61-70] and 7% [age <60]). Bleomycin toxicity was more common in older patients (age >70: grade 3-4 events 12% of the patients with discontinuation in 66%; age 61-70: 13% with discontinuation rate of 20%) compared to a 1% rate of grade 3-5 events in age <60. There was a grade 5 episode of febrile neutropenia in >70 group and 1 death related to bleomycin in age <60. With a median follow up of 8.6 years, the 10-year OS and PFS were 80.5% and 71.2%, respectively. By age-group, the 10-year OS was 88% (<60 years), 57% (61-70 years) and 15% (age >70 years); (p<0.001) (Figure 1a-b). In multivariable analysis for OS, age 61-70 (HR 2.44, p=0.002) and age >70 (HR 5.72, p=0.001), non-anthracycline based chemotherapy (HR 3.69, p<0.001), high-risk HCT-CI (HR 3.03, p=0.001) and ECOG 2-4 (HR 1.8, p=0.017), were significant. Age >70, type of chemotherapy, high-risk HCT-CI, and advanced stage were significant for PFS in the multivariable analysis (Table 2a-b). Death due to disease or toxicity at 10 years was 13.6% (age <60: 9.7%, 61-70 years: 23.2%; and for age > 70: 50.7%; [p=<0.001]) (Figure 2a-b). Multivariable analysis for cause-specific survival identified age >70 years (HR 4.04, p=<0.001), extranodal disease (HR 2.57, p=0.001) and ECOG 2-4 (HR 2.10, p=0.010) as significant predictors(Table 3). Conclusions: Age >70 years is a clinically relevant age cutoff as it has additional prognostic significance and greater rates of treatment discontinuation and toxicity compared to age 60. The HCT-CI is a useful predictor of outcome in cHL and should be validated prospectively. In multivariable analysis, age, type of treatment, comorbidity and ECOG performance status are independent predictors of OS. Further studies are ongoing to validate these findings and assess biologic differences in older versus younger cHL patients. Disclosures Tsang: Nordic Nanovector: Research Funding. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Kuruvilla:Janssen: Research Funding; Roche: Honoraria; Novartis: Honoraria; Merck: Honoraria; Gilead: Honoraria; Seattle Genetics: Consultancy; Roche: Consultancy; Merck: Consultancy; Karyopharm: Consultancy; Celgene: Honoraria; BMS: Honoraria; BMS: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Astra Zeneca: Honoraria; Janssen: Honoraria; Roche: Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria.

Alemtuzumab Plus Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allogeneic Transplantation in Ultra High-Risk CLL: Interim Analysis of a Phase II Study of the GCLLSG and fcgcll/MW

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2854-2854 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Florence Cymbalista ◽  
Véronique Leblond ◽  
Alain Delmer ◽  
Dirk Winkler ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Response Rates ◽  
Long Term Results ◽  
High Dose ◽  
Significant Difference ◽  
Ultra High Risk ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 2854 Alemtuzumab (A) proved to be efficacious in CLL patients (pts) with very poor prognosis, either due to fludarabine (F) refractoriness or due to unfavorable cytogenetics (17p-). However, rate and duration of remissions still remain unsatisfactory. Therefore, the French and German CLL study groups jointly embarked on this trial, trying to achieve higher overall response rates (ORR) by adding high-dose dexamethasone (D) to A and, simultaneously, investigating the consolidation effect of prolonged A maintenance or allogeneic stem-cell transplantation (allo-SCT), respectively. Induction treatment consisted of subcutaneous A 30 mg weekly × 3 for 28 days, combined with oral D 40 mg on days 1–4 and 15–18, and prophylactic pegfilgrastim 6 mg on days 1 and 15. Depending on the remission status, pts were treated for up to 12 weeks. If CR was documented at 4 or 8 weeks, or at least SD was achieved at 12 weeks, consolidation was scheduled with either allo-SCT or A maintenance with 30 mg every 14 days for up to 2 years (y), at the discretion of pt and physician. Between January 2008 and July 2011, 124 pts were recruited at 26 centers, 120 of whom were eligible. Pts were generally subdivided into three cohorts: 55 pts were refractory (i.e. no response or relapse within 6 months) to regimens containing F or a similar drug (i.e. pentostatin, cladribine, bendamustine). Non-refractory pts all exhibited 17p- and had either untreated (n=39) or relapsed CLL (n = 26) requiring therapy. The median age was high with 66/64/66 y in 17p- 1st line, 17p- relapse, and F-refractory pts, respectively. The three cohorts had 46/54/75% Binet C disease, 41/35/27% B symptoms, 38/42/53% reduced performance status (ECOG 1/2), median thymidine kinase levels of 35/49/24 U/L, median ß2MG levels of 3.8/5.5/4.6 mg/L, and IGHV was unmutated in 89/96/87%. In the F-refractory group, 53% exhibited 17p deletion and 22% had 11q deletion. Pretreated patients had received a median of 3 (F-refractory) or 2 prior lines (17p- relapse). 5 pts had previously undergone autologous and 1 pt allo-SCT. Treatment and efficacy data are currently available for 87 pts who completed induction therapy :17p- 1st-line (n=30), 17p- relapse (n=17), and F-refractory (n=40). Of these, 80/53/55% received the full induction of 12 weeks. ORR (best observed status) was generally high with 97/76/70%. CR was achieved in 20/0/5%. After a median follow-up of 11.8 months (mo), median progression-free survival (PFS) was 16.9/10.4/8.4 mo. Deaths are recorded in 13/27/36% of pts, with median overall survival (OS) not yet reached (>24 mo) in the 17p- 1st line group, and 15/12 mo in 17p- relapse/F-refractory pts. Consolidation treatment was performed as maintenance A (median duration 32 weeks, range 2 – 89) in 34%, and allo-SCT in 30%, with a median age of 66 and 61 y in these subgroups. The main reasons for going off-study without consolidation were death due to infection (14%, n=11, of these 6 without response, and 10 in the F-refractory cohort), CLL progression (12%), and other toxicity (5%). Among the 28 pts not receiving consolidation, there were 19 (68%) deaths, 15 of them in the F-refractory cohort. When comparing A maintenance and allo-SCT for consolidation, there were 9 (35%) and 7 (30%) PD events, respectively and there was so far no significant difference in PFS (median 17 mo in both groups) or OS. During induction, grade 3/4 hematotoxicity consisted of anemia in 28%, neutropenia in 47%, and thrombopenia in 44%. Grade 3/4 non-CMV infection occurred in 29% of 17p- 1st-line, 15% of 17p- relapsed, and 56% of F-refractory pts. CMV reactivation was observed in 54/25/40%, without severe sequelae recorded. During A maintenance, grade 3/4 toxicity consisted of neutropenia in 39% pts and thrombopenia in 4% pts with 6 SAEs (ITP, diarrhea, infection, erythema, tachycardia, and thrombosis). Conclusions: The combination of A and D shows high response rates in ultra high-risk CLL, with promising preliminary findings for PFS and OS, despite the high median age of the pts. The results compare favorably to ORR/CR of 68%/5%, and median PFS of 11.3 mo in the 17p- subgroup of the CLL8 study treated with FCR, consisting of younger pts (median 61 y). In F-refractory CLL however, when compared to the preceding CLL2H study with single agent A, the improved initial response by adding dexamethasone does not seem to translate into improved long-term results. More mature follow-up is needed, especially with respect to the impact of allo-SCT. Disclosures: Stilgenbauer: Amgen: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding. Off Label Use: Alemtuzumab in 1st line CLL treatment. Cymbalista:Roche (d) Mundipharma (e) Genzyme (e): Honoraria, Research Funding. Hinke:WiSP (CRO): Employment.

Activity and Tolerability of Azacitidine in Patients Who Relapse after Allogeneic Stem Cell Transplantation (allo-SCT) for Acute Myeloid Leukemia (AML) and Myelodysplasia (MDS): a Survey from the European Society for Blood and Marrow Transplantation (EBMT

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2506-2506 ◽  
Author(s):  
Charles Craddock ◽  
Myriam Labopin ◽  
Mohamed Houhou ◽  
Marie Robin ◽  
Juergen Finke ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
Unrelated Donor ◽  
Disease Relapse ◽  
Post Transplant ◽  
Significant Difference ◽  
Grade 3

Abstract Disease relapse is the most common cause of treatment failure after allo-SCT for high risk AML and MDS. Treatment options for patients with recurrent disease are extremely limited and re-induction chemotherapy, when administered, is often either poorly tolerated or ineffective. Azacitidine (AZA) is a DNMT inhibitor which is well tolerated and clinically active in high risk AML/MDS. Of interest AZA also up-regulates the expression of tumor antigens and plausibly augments a graft-versus-leukemia effect. A number of small studies have suggested clinical activity of AZA in patients who relapse after an allograft for AML/MDS but both overall response rate and predictors of response remain unknown. We report the first systematic study of the activity and tolerability of AZA in patients who relapsed after allo-SCT for AML/MDS. 204 patients who relapsed at a median of 6.5 months (range, 1-49) after an allograft for AML (n=130) or MDS (n=74) were studied. The median age was 58 years (range 22-76). 89 patients were transplanted using a matched sibling donor and 115 from an adult unrelated donor. 47 patients received a myeloablative and 157 a reduced intensity conditioning regimen. AZA was administered for 5-7 consecutive days every month. The median duration of AZA treatment was 68 days (inter-quartile range 24-154 days). 66 patients received additional donor lymphocyte infusions (DLI) at a median of 43 days after commencement of AZA. AZA was well tolerated in the majority of patients. 57 patients developed Grade 3-4 non-hematological toxicities 47 of which were infectious complications and likely also attributable to relapsed disease. 4 patients developed Grade 3-4 acute GVHD after AZA treatment. 45 (22%) patients achieved a complete remission (CR) or partial remission after AZA administration at a median of 114 days after commencement of treatment. 31 (15%) patients achieved a CR. The median number of courses of AZA to achieve a clinical response was three. In multivariable analysis the only significant factor determining improved response to AZA was relapse occurring more than 12 months post-transplant. The median overall survival (OS) for all patients was 6 months after the commencement of AZA therapy. In patients who achieved a CR the 2 year OS after commencement of AZA was 38.5% versus 11% for the whole population (p= 0.001). In multivariable analysis OS was determined by the occurrence of disease relapse more than 6 months post-transplant and achievement of a CR after AZA therapy. Of note, there was no significant difference in response rates to AZA between patients with relapsed AML or MDS. Concurrent administration of DLI did not improve either response or survival rates. In conclusion, these data confirm the ability of AZA to salvage a proportion of patients with AML or MDS who relapse after an allogeneic SCT and identify prognostic factors of response. The response and survival rates achieved with salvage AZA are comparable to those previously reported with either intensive chemotherapy or DLI. We conclude AZA represents an important and relatively well-tolerated new treatment option in the management of selected patients with AML and MDS who relapse after allo-SCT. Disclosures Craddock: Celgene: Grants Other, Honoraria. Kroger:Celgene: Research Funding. Mohty:Celgene: Research Funding.

Age Differences in Disease Characteristics, Patterns of Care, and Outcomes of Follicular Lymphoma (FL) in the United States (US): Report From the National Lymphocare Study (NLCS)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3708-3708
Author(s):  
Chadi Nabhan ◽  
Michelle Byrtek ◽  
Shadi Latta ◽  
Keith L Dawson ◽  
Xiaolei Zhou ◽  
...  
Keyword(s):  
Research Funding ◽  
Age Groups ◽  
Age Group ◽  
Employment Equity ◽  
Disease Characteristics ◽  
Baseline Factors ◽  
Equity Ownership ◽  
Grade 3 ◽  
The Impact ◽  
To Receive

Abstract Abstract 3708 Background: There are few prospective studies on disease characteristics, patterns of care, response, and outcomes in elderly FL patients (pts) in the US. The NLCS is a Genentech-sponsored prospective multicenter registry study that collects this information without study-specific treatment. We utilized the NLCS database to better understand the impact of age on FL outcome. Patients and Methods: All evaluable pts with FL histology in the NLCS were included except pts with FL plus other lymphoma histology or pts who progressed before first treatment or before being assigned to watchful waiting (WW). Using Pearson Chi-Square tests, associations of age groups (≤60, 61–70, >70) with disease characteristics and overall response (ORR) were examined. Median PFS and OS by treatment regimen were estimated using Kaplan-Meier methods for each age group. Cox proportional hazards regression adjusted for baseline factors (grade, number of nodal sites, LDH, Hgb, stage, performance status (PS), bone marrow (BM) involvement, race, and treatment center type) were used to assess treatment differences in PFS and OS and the significance of age by treatment interactions. Results: Of 2,647 pts, 47% (n=1,254) were ≤60 yrs, 25% (n=666) were 61–70 yrs, and 27% (n=727) were >70 yrs (min age of 22; max of 97). Compared with pts ≤60 yrs, pts 61–70 and >70 were more likely to be white (93% >70, 92% 61–70, and 88% ≤60, P=.02 and .02 respectively), have stage I/II disease (37% >70, 36% 61–70, and 29% ≤60, P=.0008 and .0003), have <5 nodal sites (73% >70, 69% 61–70, and 61% ≤60, P=.001 and <.0001), and have poor-risk FLIPI (53% >70, 51% 61–70, and 15% ≤60, P<.0001 and <.0001). Compared with pts ≤60, elderly pts (>70) were more likely to have FL grade 3 (24% vs 18%, P=.01). While there were no differences in geographic distribution by age, elderly pts were more likely to receive therapy at community practices (86%) versus academic institutions than pts ≤60 (77%, P<.0001) or 61–70 (81%, P=.004). Treatments varied significantly by age (P<.0001). More elderly pts were observed compared to pts ≤60 (23% vs19%). When treated, elderly pts (22%) were more likely to receive rituximab (R) monotherapy compared with patients aged 61–70 (12%) or ≤60 (10%). When chemotherapy alone or plus R was given, elderly pts were less likely to receive anthracyclines (45% vs 65% (61–70) and 68% (≤60)). Among all variables, only grade 3 histology predicted anthracycline use in all age groups. Lack of BM involvement predicted anthracycline use for younger pts (≤60 and 61–70). Of those ≤60, white pts were more likely to receive anthracyclines, and of those 61–70, those with ≥5 nodal sites were more likely to receive anthracyclines. ORRs were similar across age groups receiving similar regimens with R plus chemo providing the highest ORR. Adjusting for baseline factors, treatment (WW, R, R-Chemo, or other) benefit varied for each age group in terms of PFS (P=.02), with treatment outcomes being most differentiated among younger pts (Table). PFS appeared shorter in elderly pts regardless of the treatment received. No significant interaction between age and efficacy of anthracycline in terms of PFS or OS was observed (P-values >.65), but the overall effect of anthracycline for all pts was beneficial for PFS (HR=0.80, P=.02) and OS (HR=0.67, P=.003). Median OS was 8 years for elderly and not reached for others. After adjusting for baseline factors, no significant differences in treatment impact by age on OS were seen. Elevated LDH, reduced Hgb, stage III/IV, PS ≥1, and BM involvement were all significantly associated with shortened OS. These factors were also significantly associated with treatment choice, as worse-prognosis elderly pts were more likely to receive either R or R+chemo than WW or other treatment. Conclusions: FL pts >70 yrs more commonly received R alone and less commonly received anthracyclines when treated with chemotherapy. The impact of anthracyclines on PFS did not vary by age, but differences in PFS for other treatment regimens showed a stronger association among younger pts Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau. Byrtek:Genentech, Inc., a member of the Riche Group: Employment, Equity Ownership. Dawson:Genentech, Inc., a member of the Riche Group: Employment, Equity Ownership. Link:Genentech, Inc., a member of the Riche Group: Consultancy; Celgene: Consultancy; Spectrum: Consultancy. Friedberg:Genentech: Consultancy. Cerhan:Genentech: National LymphoCare Scientific Advisory Board Other. Flowers:Celgene: Consultancy; Prescription Solutions: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy, Research Funding; Genentech: Consultancy; GIlead: Research Funding; Spectrum: Research Funding; Janssen: Research Funding; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees.

Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 0801

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 614-614
Author(s):  
Paul M. Barr ◽  
Hongli Li ◽  
Richard Burack ◽  
Michael LeBlanc ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Free Survival ◽  
Grade 3

Abstract Background: Despite an abundance of effective therapeutic options, advanced stage follicular lymphoma (FL) remains incurable. Further, prospective trials consistently demonstrate that 20% of patients relapse within 2 years and ultimately have an inferior survival (Casulo 2015). Maintenace rituximab following chemoimmunotherapy induction is able to delay disease progression but has not demonstrated a benefit in overall survival (Salles 2011). Additionally, radioimmunotherapy (RIT) is one of the most effective single agent options in FL but is not commonly utilized as part of upfront treatment. As such, the role of both remains unclear. Based on results demonstrated with RIT consolidation in SWOG 0016 and the efficacy of rituximab maintenance, SWOG 0801 was designed as a phase 2 single arm trial, conducted to evaluate the utility of consolidative RIT and sequential maintenance rituximab following chemoimmunotherapy induction. Methods: Eligible patients (pts) with treatment naïve stage III/IV or bulky stage II FL received RCHOP for 6 cycles (without rituximab for the last 2 cycles) followed by iodine-131 tositumomab and subsequent rituximab administered every 3 months for up to 4 years. The primary endpoint was progression-free survival (PFS) at 3 years. Secondary endpoints included 5-year overall survival (OS), overall response rate (ORR), and safety. Results: Of 87 pts registered to this study, 85 were deemed eligible following central pathologic review. One additional patient withdrew consent and received no treatment on protocol. Of the 84 evaluable patients, the median age was 52 years (range 29 - 80) ) and 18%, 40%, and 42%had low, intermediate and high risk FLIPI scores, respectively. Seventy-three pts completed RCHOP and I-131 tositumomab. Grade ≥3 AEs occurring ≥5% of pts included neutropenia (57%), leukopenia (40%), thrombocytopenia (20%), febrile neutropenia (17%), fatigue (10%), neuropathy (8%), anemia (7%) and hyperglycemia (5%). Reasons for discontinuation included refusal of tositumumab (6 pts), prolonged myelosuppression (2 pts), ascites (1pt), inability to provide tositumumab (1 pt), and an unrelated lower extremity wound (1 pt). Following induction and RIT, 59 complete responses and 23 partial responses were observed, for a ORR of 99% (95% CI: 93.5%, 99.9%) Sixty nine eligible patients registered to maintenance therapy with 42 completing the 4 year treatment plan. The only grade ≥3 AE that occurred in ≥5% of pts was leukopenia (5%). Twenty-seven pts discontinued maintenance therapy, including 11 in the first 2 years and 16 in the last 2 years, due to the following reasons: infection (8 pts), patient preference (8 pts), deaths (2 pts), treatment delay (2 pts), secondary solid tumors (2 pts), bowel perforation (1 pt), joint pain (1 pt), hepatic transaminase elevation (1 pt), insurance refusal (1 pt), and dose error (1 pt). Four additional secondary malignancies were reported following completion of therapy including solid tumors (3 pts) and AML (1 pt). To date, 9 deaths have occurred due to secondary malignancies (3 pts), unknown etiology (3 pts), cardiac arrest (2 pts) and non-alcoholic cirrhosis (1 pt). After median follow-up of 5.6 years (range 3-7 years), 17 events have occurred including 9 pts experiencing progressive FL resulting in a progression free survival of 90% (95% CI: 81.9%, 95.1%) at 3 years and 84%(95% CI: 74.5%, 90.6%) at 5 years (Figure). Three-year overall survival is 96% (95% CI: 89.3%, 98.8%) and 5-year overall survival is 94% (95% CI: 86.2%, 97.5%). Conclusions: SWOG 0801 demonstrates near universal responses following chemoimmunotherapy and RIT. This sequential therapeutic strategy appears to improve early outcomes as 94% of pts are without disease progression at 2 years, consistent with the best results ever demonstrated for FL in the National Clinical Trials Network. However, the majority of discontinuations occurred during maintenance suggesting that rituximab over a 4-year span is not feasible for many patients due to cumulative toxicity. Future studies investigating precision strategies in high-risk FL may consider an aggressive chemoimmunotherapy induction and RIT consolidation platform to overcome early FL progression given these promising outcomes. Support: NIH/NCI grants CA180888, CA180819, and in part by GlaxoSmithKline. Figure. Progression-Free Survival and Overall Survival Figure. Progression-Free Survival and Overall Survival Disclosures Barr: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Smith:Amgen: Other: Educational lecture to sales force; Juno: Consultancy; Pharmacyclics: Consultancy; AbbVie: Consultancy; Portola: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; TGTX: Consultancy. Gopal:Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy. Persky:Merck: Research Funding; Gilead: Speakers Bureau. Press:Roche / Genentech: Consultancy, Research Funding. Fisher:Gilead: Consultancy; Seattle Genetics: Consultancy; Johnson and Johnson: Consultancy. Friedberg:Bayer: Other: Data Safety Monitoring Committee.

Allogeneic Stem Cell Transplantation (SCT) for Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) in Elderly Patients (Older than 60 Years)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2025-2025
Author(s):  
Michele Pohlen ◽  
Christoph Groth ◽  
Tim Sauer ◽  
Dennis Görlich ◽  
Rolf Mesters ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Treatment Outcomes ◽  
Cell Transplantation ◽  
Older Patients ◽  
Conventional Treatment ◽  
Advanced Disease ◽  
Disease Status ◽  
Risk Models ◽  
The Impact

Abstract Allogeneic SCT is the most potent post-remission therapy for AML patients, particularly in patients aged >40-45 years, and the only curative option for patients with refractory AML or with high-risk MDS. Although median age at diagnosis is above 65 years for both entities, for patients aged 60 years or older, studies evaluating allogeneic SCT as post-remission therapy or as salvage therapy are limited. Dose adapted / reduced conditioning for patients in remission and sequential conditioning (intensive chemotherapy followed by dose adapted conditioning), for patients with active leukemia / high-risk disease, together with improvement in supportive care, have shown improved outcome results for SCT in younger and older patients. Aiming to predict treatment outcomes of patients undergoing allogeneic SCT, various transplant specific risk models have been introduced in the past. Assuming that these risk models might be of value especially in older patients, we performed a retrospective single center analysis of transplanted patients, incorporating the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), the European Group for Blood and Marrow Transplantation (EBMT) Score and the Disease Risk Index (DRI). Between 1999 and 2014, 187 patients (pts) with AML (87%) or MDS (13%) aged ≥60 years (median age of 64 years, range 60 - 77 years) received an allogeneic SCT at our institution, either from a HLA-identical related (50 pts.), HLA-matched unrelated (103 pts.), or an HLA-mismatched donor (34 pts). Median follow-up of surviving patients was 36 months (range 1 to 173 months). All patients with AML received a cytarabine-based standard induction therapy. Conditioning prior to transplant consisted of dose reduced / dose adapted therapy (TBI-, busulfan- or treosulfan-based) or sequential conditioning (for patients with high risk or refractory disease). Thirty-nine of the 47 AML patients transplanted in first complete remission (CR1) had a high-risk AML, defined by an adverse cytogenetic risk profile (16 pts), persisting AML after first induction therapy (12 pts), a secondary AML (6 pts.), or persisting / increasing minimal residual disease (5 pts). MDS patients had mainly an advanced disease with blast count 10-19% (19/24 pts). For all patients, an overall survival (OS) at 3 years of 35% (95% CI: 27-42%) was observed. Cumulative incidences of NRM and relapse at one year were 37% and 22%, respectively. Patients transplanted in CR1 showed a 3-year OS of 49%, whereas patients transplanted in subsequent remission, with active AML, or high-risk MDS had a 3-year OS of 26%, 28% and 31%, respectively. Univariate analysis of the whole group showed that advanced and/or active disease (advanced/active AML/MDS vs. AML CR1, p = .04), high DRI (high/very high vs. low/intermediate, p = .06), and poor Eastern Cooperative Oncology Group Score (ECOG; ≥2 vs. 0 or 1, p=.0001), were associated with an inferior OS. Patient age had no impact on outcome parameters. In a multivariate analysis of disease / transplant related risk factors (status pre transplant, EBMT-score, HCT-CI and DRI) only disease status pre transplant was an independent prognostic factor for OS (active / advanced disease vs. CR1, hazard ratio 1.55; 95% CI 1.01-2.38). These results indicate that patient's age ≥60 years in general is no limiting factor for an allogeneic transplant, even if refractory to conventional treatment. Pre-transplant selection of patients eligible for intensive treatment was most likely one relevant bias in our analysis, limiting the determination of the impact of preexisting comorbidities on treatment outcomes. Given the prognostic impact of the disease status at transplant, the improvement of transplant results in elderly patients, and the dismal prognosis of older patients with myeloid neoplasms receiving conventional treatment, the impact of allogeneic SCT, especially in early disease stages / CR1 of patients with MDS / AML eligible for intensive treatment has to be further studied in prospective trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Oral Azacitidine (CC-486) Plus R-CHOP in Patients with High-Risk or Previously Untreated Diffuse Large B-Cell Lymphoma, Grade 3B Follicular Lymphoma, or Transformed Lymphoma (AFT-08)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2964-2964 ◽  
Author(s):  
Peter Martin ◽  
Nancy L. Bartlett ◽  
Julio C. Chavez ◽  
John L. Reagan ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Board Of Directors ◽  
Dose Escalation ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Grade 3

Abstract Background: For patients with diffuse large B-cell lymphoma (DLBCL), resistance to standard R-CHOP immunochemotherapy remains an urgent and unmet clinical challenge. Aberrant DNA methylation likely contributes to chemoresistance and may represent a therapeutic target.In a phase I study of R-CHOP plus subcutaneous azacitidine, a DNA methyltransferase inhibitor, complete responses (CRs) were achieved in 10/11 high-risk DLBCL patients (Clozel et al. Cancer Discovery 2013), providing the rationale for this study of oral azacytidine (CC-486) plus R-CHOP. Previously reported data from the dose escalation phase of this study demonstrated promising response rates in patients with high-risk DLBCL (Martin et al. Blood 2017). Here, we present results from both the dose escalation and expansion phases after substantially longer follow-up. Methods: CC-486-DLBCL-001 (NCT02343536) is a phase I, open-label, multicenter study of CC-486 plus standard R-CHOP in patients with previously untreated DLBCL, grade 3B follicular lymphoma (FL), or transformed FL. Eligible patients were aged ≥18-80 years with no active viral hepatitis, had an International Prognostic Index (IPI) score ≥2 or DLBCL double-positive for BCL2 and c-MYC, an Eastern Cooperative Oncology Group performance status ≤2, and Ann Arbor stage II-IV disease. Patients in the dose escalation phase were enrolled sequentially into 4 dose cohorts of CC-486 (100, 150, 200, and 300 mg) using the time-to-event continual reassessment method. Additional patients were enrolled in the expansion phase to evaluate preliminary efficacy. Patients received up to six 21-day cycles. CC-486 was administered for 7 days before initiation of R-CHOP and on days 8-21 of cycles 1-5. Granulocyte-colony stimulating factor was mandated by protocol and anti-emetics were standard treatment. The primary objectives were to determine safety (per NCI CTCAE v4.03) and the recommended phase 2 dose (RP2D) of CC-486 in combination with standard R-CHOP. Secondary endpoints included pharmacokinetics and preliminary efficacy per the International Working Group criteria (Cheson et al.J Clin Oncol 2014). Results: Fifty-nine patients were enrolled as of May 31, 2018, including 40 treated at the RP2D of CC-486 300 mg. The median age in the overall population was 66 years (range, 25-80), 76% were aged >60 years, 59% were male, and 59% had an IPI score ≥3. Fifty-four patients (92%) completed all 6 planned cycles of study treatment. Thirteen patients (22%) had CC-486 dose reductions because of adverse events (AEs). Two patients discontinued CC-486 due to AEs: febrile neutropenia (n=1; 150 mg) and sepsis (n=1; 300 mg). The most common AEs were gastrointestinal, which were mainly grade 1/2; hematologic AEs were the most common grade 3/4 toxicity (Table 1). Grade 3/4 AEs related to CC-486 occurred in 36 (61%) patients, most commonly neutropenia (41%) and febrile neutropenia (20%). Febrile neutropenia was more common among older patients (9/15 patients with this AE were aged >70 years) and those with IPI scores ≥3 versus ≤2 (31% vs 17%) but was not correlated with CC-486 dose. One patient died during the study (acute respiratory failure possibly related to study treatment). All patients were evaluable for response. The overall response rate was 95%, with 52 patients (88%) achieving a CR; response rates were generally similar in patients with IPI scores ≥3 and ≤2 and in patients treated at the RP2D (Table 2). Median progression-free survival (PFS) was not reached (median follow-up of 12 months); estimated 1-year PFS rates were similar in the overall population (86%) and in patients with IPI scores ≥3 (84%) and ≤2 (89%). Conclusions: Epigenetic priming with CC-486 before R-CHOP demonstrated promising clinical activity in patients with high-risk, previously untreated DLBCL, transformed FL, or grade 3B FL. AEs were generally consistent with the known safety profile of azacitidine and toxicities associated with R-CHOP. These results support further investigation of oral azacitidine (CC-486) in combination with R-CHOP, including patients with high-risk disease. Disclosures Martin: Gilead: Consultancy; Janssen: Consultancy; Kite: Consultancy; AstraZeneca: Consultancy; Seattle Genetics: Consultancy; Bayer: Consultancy. Bartlett:Astra Zeneca: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; ImaginAB: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed: Research Funding; Pharmacyclics: Research Funding; Millennium: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck & Co: Research Funding; Pharmacyclics: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Novartis: Research Funding; Immune Design: Research Funding. Chavez:Merck: Research Funding; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; Humanigen: Consultancy. Reagan:Alexion: Honoraria; Takeda Oncology: Research Funding; Pfizer: Research Funding. Smith:Portola: Honoraria; BMS: Consultancy. LaCasce:Seattle Genetics: Consultancy, Honoraria; Humanigen: Consultancy, Honoraria; Bristol-Myers Squibb: Other: Data safety and monitoring board; Research to Practice: Speakers Bureau. Jones:Celgene: Employment, Equity Ownership. Drew:Celgene Corp.: Employment. Wu:Celgene: Employment, Equity Ownership. Cerchietti:Celgene: Research Funding; Weill Cornell Medicine: Employment. Leonard:ADC Therapeutics: Consultancy; Karyopharm: Consultancy; MEI Pharma: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Genentech/Roche: Consultancy; BMS: Consultancy; Juno: Consultancy; Celgene: Consultancy; Biotest: Consultancy; Novartis: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Sutro: Consultancy; United Therapeutics: Consultancy.

Incidence of febrile neutropenia and effectiveness of pegfilgrastim prophylaxis in patients with advanced-stage solid tumors receiving chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20564-e20564
Author(s):  
Jeffrey Crawford ◽  
Maureen Reiner ◽  
Phuong Khanh H. Morrow ◽  
Gary H. Lyman
Keyword(s):  
Febrile Neutropenia ◽  
Solid Tumors ◽  
Phase Iii ◽  
Disease Stage ◽  
Advanced Stage ◽  
Test Results ◽  
Advanced Disease Stage ◽  
Grade 3 ◽  
Advanced Stage Cancer ◽  
The Impact

e20564 Background: Advanced disease stage has been identified as an independent risk factor for the development of febrile neutropenia (FN), which continues to be associated with substantial morbidity. We report here results from two clinical trials on the impact of pegfilgrastim (PEG) in patients with advanced stage solid tumors. Methods: Patients were pooled from two placebo-controlled trials: a) a phase III trial of 928 patients with breast cancer, randomized to placebo or PEG 6 mg on day 2 of each 21-day cycle (Vogel CL, et al. JCO 23:1178-84, 2005); and b) a phase II trial of 241 patients with colorectal cancer (CRC), randomized to placebo or PEG 6 mg on day 4 of each 14-day cycle (Hecht JR et al. Clin CRC 9:95-101, 2010). Patients were grouped by disease stage at baseline: advanced (stage III, IIIA, IIIB, IV) or limited (stage I, II, IIA, IIB). Grade 3/4FN was defined as a temperature of ≥ 38.2°C and an ANC of <1.0 x 109/L. The Cochran-Mantel-Haenszel test was used to evaluate the association between PEG and grade 3/4 FN, odds ratio (OR) for FN was estimated by logistic regression, and a trend in the number of FN events per patient was estimated using a Cochran-Armitage test. Results: Characteristics of the 982 patients with advanced stage cancer are shown in the table. PEG was associated with significantly fewer grade 3/4 FN events (p < 0.001), with OR for PEG vs placebo of 0.12 (95% CI: 0.07, 0.22). The percentage of patients with 0, 1, and ≥ 2 FN events was 97%, 3%, and 0% with PEG and 81%, 18%, and 0.4% with placebo, and PEG significantly reduced the number of FN events (p< 0.001). Conclusions: Patients with advanced stage cancer are at considerable risk for developing FN, and PEG prophylaxis reduced that risk. Assessment of FN risk is essential in the advanced/metastatic treatment setting. [Table: see text]

Chemotherapy-induced diarrhea in older patients with colorectal cancer receiving fluoropyrimidines: A retrospective review.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14647-e14647
Author(s):  
Laxmi H Iyer ◽  
Ilene S. Browner ◽  
Amanda L. Blackford ◽  
Daniel A. Laheru ◽  
Nilofer Saba Azad ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Older Patients ◽  
Medical Center ◽  
Gender Performance ◽  
Advanced Stage ◽  
Specific Data ◽  
Severe Diarrhea ◽  
Patient Demographics ◽  
Grade 3 ◽  
The Impact

e14647 Background: Chemotherapy-induced diarrhea (CID) is a common treatment-limiting toxicity of regimens used for colorectal cancer (CRC). Fluoropyrimidines, the backbone of CRC regimens, are associated with diarrhea, but the frequency and severity in older patients are less known due to under-representation of older patients in CRC trials. As life expectancy increases, the prevalence of older CRC patients will increase. We aimed to evaluate if older patients are vulnerable to CID. Methods: We retrospectively studied patients >70 years old who received fluoropyrimidines based therapy for stages II-IV CRC at Johns Hopkins and Bayview Medical Center from 1996-2007. Patient demographics and cancer-specific data were retrieved. Diarrhea was graded per National Cancer Institute Clinical Toxicity Criteria. Results: We included 150 patients > 70 years old. Median age was 75 (range 70-87). 65 (43%) were 70-74 years old, 52 (35%) were 75-79 years and 33 (22%) > 80. Diarrhea occurred in 48% (n=72) of patients. Presence of diarrhea was not significantly associated with increasing age (70-74, 75-79 or >80 years), gender, ECOG performance, number of comorbidities or medications. Severe grade 3-4 diarrhea occurred in 16% (n=24) and was associated with advanced stage (p=0.04). CID (all grades) was more common in cycle 1 than subsequent cycles (p=0.002). Conclusions: Fluoropyrimidines based therapy was tolerated in older patients with CRC. Incidence of CID was not associated with increasing age, gender, performance, comorbidities or polypharmacy. Severe diarrhea occurs in advanced stage and early during therapy. Larger prospective studies are needed to definitively evaluate the impact of age on CID.

scholarly journals Toxicities and Related Outcomes of Elderly Patients (pts) (≥65 Years) with Hematologic Malignancies in the Contemporary Era (Alliance A151611)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 536-536
Author(s):  
Michael Tallarico ◽  
Jared Foster ◽  
Drew Seisler ◽  
Jacqueline Lafky ◽  
Arti Hurria ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Biologic Therapy ◽  
Group Differences ◽  
Age Group ◽  
Advisory Committees ◽  
Treatment Type ◽  
Treatment Interaction ◽  
Grade 3 ◽  
The Impact

Abstract Background: Contemporary approaches to non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) incorporate chemo-immunotherapy, biologic combinations, and immune modulating agents; toxicities in elderly pts (³65 years) receiving these therapies are not well studied. Further, clinical and biologic factors predicting these toxicities in pts receiving biologic therapy remain undefined. Methods: We reviewed data on NHL and/or CLL pts treated prospectively on 14 studies by the Alliance for Clinical Trials in Oncology from 2004-2014 (Table 1). Toxicity was assessed per the NCI CTCAE at the time of trial enrollment, and the probabilities of experiencing grade 3 and grade 4 hematologic (hem) and non-hematologic (non-hem) toxicities were modeled as a function of age (³65 years vs. < 65), time on study, treatment (biologics only vs. biologic + chemotherapy), gender, race, LDH, performance status (PS), stage, and an age-by-treatment interaction using logistic regression. Results: A total of 1199 pts (409 age ³ 65; 790 age < 65; 736=CLL and 463=NHL) were included. Among these patients, 493 received only biologic therapy (166 age ³ 65; 327 age < 65; 104 CLL; 389 NHL), and 706 received biologic + chemotherapy (243 age ³ 65; 463 age < 65; 632 CLL; 74 NHL). Among CLL pts (259 pts ³ 65), the effect of age on the probability of experiencing a grade 3 heme toxicity differed by treatment type (age-by-treatment interaction p = 0.047). Specifically, the adjusted odds ratio (OR) (age ³ 65 vs. < 65) for pts receiving only biologic therapy was 3.075 (95% CI: 1,15-8.25), and that for pts receiving biologic + chemotherapy was 1.044 (95% CI: 0.69 - 1.57). Similar results were seen in CLL pts for grade 4 heme toxicities (age-by-treatment interaction p = 0.033; biologic OR 6.937, 95% CI: 1.76-27.35; biologic + chemo OR 1.484, 95% CI: 1.04-2.13). No such interactions were found in CLL pts for grade 3 and 4 non-hem toxicities; however, older pts had significantly higher odds of experiencing a grade 3 non-hem toxicity than younger pts (adjusted OR 1.40; p = 0.047; 95% CI: 1.004-1.96). No age group differences were found in CLL pts for grade 4 non-hem toxicity. Similar analyses were performed for NHL pts (150 pts ³ 65), but no significant age group differences were found. Among CLL pts, women had significantly higher odds of experiencing a grade 3 heme toxicity than men (OR 2.01; p = 0.0007); no difference in grade 3 non-hem or any grade 4 toxicity was noted. Non-Caucasian CLL pts had higher odds of experiencing a grade 4 non-hem toxicity than Caucasians (OR 2.892; p = 0.0029), but no other toxicity differences were found. Worse PS was associated with increased toxicities (OR 1.871; p = 0.0009: grade 3 heme; OR 1.647; p = 0.0025: grade 3 non-hem; OR 1.410; p = 0.0448: grade 4 heme, and OR 1.931; p = 0.0252: grade 4 non-hem). CLL pts with advanced stage disease had higher odds of experiencing a heme toxicity (grade 3: OR 1.95; p = 0.0007, grade 4: OR 1.451; p = 0.0329), but no stage associations were found for non-hem toxicities. Among NHL pts, men had significantly higher odds of experiencing a grade 4 hematologic toxicity than women (OR 4.351; p = 0.0169), but no other toxicity differences were found. An increase in LDH was associated with significantly higher odds of experiencing grade 3 non-hem and grade 4 heme toxicities (grade 3 non-heme: OR 1.633; p = 0.021, grade 4 heme: OR 2.039, p = 0.0182), but no such effect was found for grade 3 heme or grade 4 non-hem. Worse PS was associated with higher odds of experiencing grade 3 toxicities (heme: OR 2.025; p = 0.0344, non-hem: OR 2.458; p = 0.0013), but no such differences were found for grade 4 toxicities. No significant stage or race effects were found in NHL patients. Conclusion: In pts ³65 years who have CLL or NHL, we identified several clinical and disease-related factors as potential predictors of developing grade 3 and/or 4 heme and non-hem toxicities (Table 2). A prognostic model is being constructed to predict toxicities in these under-studied pts to guide management and monitoring. Further, the impact of these toxicities on outcomes is being analyzed and will be presented at the meeting. Disclosures Hurria: Celgene: Other: Research; Optum Health Care SOlutions: Consultancy, Other: Conference panel, research; Boehringer Ingelheim Pharmaceuticals: Consultancy; Sanofi: Consultancy; Carevive: Consultancy; Novartis: Other: Research; GTx, Inc: Consultancy. Bartlett:Gilead: Consultancy. Cheson:Gilead: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nabhan:Infinity: Consultancy; Abbvie: Consultancy; Cardinal Health: Consultancy; Seattle Genetics: Research Funding; Genentech: Consultancy, Research Funding; Astellas: Research Funding; Celgene Corporation: Consultancy, Research Funding.

Determinants of Choice of Front-Line Tyrosine Kinase Inhibitor for Chronic Phase CML: A Study from the "Registro Italiano LMC & Campus CML"

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-36
Author(s):  
Mario Tiribelli ◽  
Roberto Latagliata ◽  
Massimo Breccia ◽  
Isabella Capodanno ◽  
Maria Cristina Miggiano ◽  
...  
Keyword(s):  
High Risk ◽  
Tyrosine Kinase ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Multivariable Analysis ◽  
Chronic Phase ◽  
Front Line ◽  
Line Therapy ◽  
Concomitant Medications

Introduction : therapy of chronic phase (CP) chronic myeloid leukemia (CML) is based on tyrosine kinase inhibitors (TKIs) in virtually all patients. Three TKIs are approved for first-line therapy in Italy: imatinib and two second-generation (2G) TKIs, dasatinib and nilotinib. Choice of the front-line TKI is based on a combined evaluation of patient's and disease characteristics, age, risk, comorbidities and concomitant medications. Treating physician's preference and, in some cases, economic considerations, particularly after the advent of generic imatinib, may play a role in TKI selection. However, to date, few data are available on TKI use in a whole nation and on the possible drivers of treatment choice. Aim of the present work was to analyse the use of front-line TKI therapy in a large, unselected cohort of Italian CP-CML patients, correlating patient's features to drug choice. Methods: in the framework of the national Campus CML program, we retrospectively evaluated 1422 patients with CP-CML diagnosed from 2012 and 2019 in 21 haematologic Centres, mostly in academic and/or tertiary hospitals, widespread through the entire Italian territory and treated frontline with imatinib, dasatinib or nilotinib. Results: median age at diagnosis was 59.9 years [interquartile range (IQR) 47.1 - 71.7], with 317 (22.3%) patients under 45 years, 552 (38.8%) between 45 and 65 years and 553 (38.9%) older than 65 years; 821 (57.7%) patients were males. Among 1364 evaluable patients, CML risk according to Sokal score was low in 540 (39.6%), intermediate in 610 (44.7%) and high in 214 (15.7%) patients respectively; the number at low, intermediate or high risk according to the novel ELTS score among 1325 evaluable patients was 759 (57.3%), 402 (30.3%) and 164 (12.4%) respectively. Considering comorbidities, 1003 (70.6%) patients had at least one active disease at the time of CML diagnosis, the most common being hypertension (n=547, 38.5%), previous neoplasms (n=185, 13.0%), diabetes (n=150, 10.6%), chronic bronchopulmonary diseases (n=114, 8.0%), acute myocardial infarction (n=95, 6.7%), previous stroke (n=36, 2.5%) and other vascular diseases (n=98, 6.9%). Among 1335 evaluable patients, 813 (60.9%) were taking at least one concomitant medication, with 280 (21.0%) taking 3-5 drugs and 140 (10.5%) taking 6+ drugs at time of TKI start. As to the frontline therapy, 794 (55.8%) received imatinib and 628 (44.2%) were treated with 2G-TKIs, (226 dasatinib and 402 nilotinib) respectively. According to age, 2G-TKIs were chosen for majority of patients aged &lt;45 (69.1%) while imatinib was used in 76.9% of patients over 65 (p&lt;0.001). There was a predominance of imatinib use across all Sokal (51.1% in low, 61.3% in intermediate and 51.4% in high) and ELTS (50.3% in low, 60.4% in intermediate and 66.5%) risk categories. We observed a prevalent use of 2G-TKIs in patients presenting with higher WBC counts (55.1% if WBC &gt;100,000/mm3 vs 38.2% if WBC &lt;100,000/mm3; p&lt;0.001), lower Hb (53.8% if Hb &lt;10 g/dl vs 41.9 if Hb &gt;10 g/dl; p=0.001) and bigger spleen (65.1% if spleen &gt;5 cm vs 44.8% if spleen 1-5 cm vs 37.3% if spleen not palpable; p&lt;0.001). There was a decreasing use of 2G-TKIs with higher number of concomitant drugs: 64.4% for 0, 47.7% for 1-2, 27.0% for 3-5 and 13.6% for &gt;5 drugs, respectively (p&lt;0.001). Concordantly, there was a significant higher use of imatinib in patients with hypertension (69.8%), diabetes (70.0%), COPD (73.7%), previous neoplasms (73.0%), AMI (86.3%) or stroke (97.2%) history (p&lt;0.001 for all conditions). Lastly, we observed a wider use of imatinib (61.1%) in patients diagnosed in years 2018-19, compared to those of the period 2012-17 (53.7%; p=0.01). In multivariable analysis, factors correlated with imatinib use were age &gt; 45 years, intermediate or high Sokal risk, presence of some comorbidities (2nd neoplasia and stroke) and number of concomitant medications. Conclusions: preliminary results of this observational study on almost 1500 patients show that around 55% of newly diagnosed Italian CP-CML patients receive imatinib as front-line therapy, and that the use of 2G-TKI is prevalent in the younger patients and in those with no concomitant clinical conditions. The counterintuitive finding of imatinib prevalence as frontline treatment in high risk patients might be explained by the older age of these patients. Introduction of the generic formulation in 2018 seems to have fostered the use of imatinib. Figure Disclosures Breccia: Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Saglio:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Ariad: Research Funding; Roche: Research Funding.

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