scholarly journals Spirit 2: Final 5 Year Analysis of the UK National Cancer Research Institute Randomized Study Comparing Imatinib with Dasatinib in Patients with Newly Diagnosed Chronic Phase CML

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 457-457 ◽  
Author(s):  
Stephen O'Brien ◽  
Leanne Cork ◽  
Valeria Bandeira ◽  
Ruth Bescoby ◽  
Letizia Foroni ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Board Of Directors ◽  
Research Funding ◽  
Molecular Response ◽  
Event Free Survival ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Objective. SPIRIT 2 is the largest phase 3 prospective randomized open-label trial comparing imatinib (I) 400mg with dasatinib (D) 100mg daily in newly diagnosed chronic phase CML. The primary endpoint was 5 year event-free survival. Methods. 812 (406 in each arm) of 814 patients recruited started study medication (median age 53.2, 275/812 (33.8%) were over 60 years old). Patients were recruited at 144 hospitals between August 2008 and March 2013 and randomized to receive either imatinib 400mg or dasatinib 100mg daily. Secondary endpoints included overall survival, rates of treatment failure, cytogenetic/molecular response - RT-PCR BCR-ABL/ABL ratio of <0.1%IS(major molecular response (MMR), 3 log reduction, MR3) and deeper. To address the potential confounding effect on the primary endpoint of patients switching from randomized treatment to an alternative TKI or other treatment, exploratory per-protocol analyses were performed using the inverse probability of censoring weighting (IPCW) method.Results. All patients have now completed 5 years of follow-up. 424/812 (52.2%) patients completed the study whilst still taking first line medication: 230/406 (56.7%) on dasatinib, 194/406 (47.8%) on imatinib. Of the patients who discontinued first line therapy, more patients on the imatinib arm switched due to suboptimal PCR response (as decided by the local investigator) than on dasatinib (D7/406, 1.7%; I71/406, 17.4%) but more patients on the dasatinib arm discontinued due to intolerance (D123/406, 30.3%; I68/406, 16.7%). More patients went on to transplant in the imatinib arm than in the dasatinib arm (D 6/406, 1.5%; I 30/406 7.6%) and in the imatinib patients undergoing transplant the reason for first line treatment failure was disease progression in 5/30 and suboptimal molecular response in 11/30. Using an intention to treat analysis cumulative incidence of MR3 and MR4 on first line therapy within 5 years was higher in the dasatinib arm than the imatinib arm (MR3: D 83.0%, I 63.0% - difference 20.0%, p<0.0001; MR4: D 77.5%, I 57.2% - difference 20.3%, p<0.0001).At 24 months the complete cytogenetic response rate was D 42.6%, I 31.8% - difference 10.8%, Chi-square test p=0.001.At 5 years the probability of treatment failure-free survival was higher with dasatinib than imatinib(D60.9%, I52.9% - HR: 0.73 (95%-CI:0.59-0.90), p=0.004) but there were no significant differences in event free survival (D91.0%, I89.0% - HR:0.80 (95%-CI:0.51-1.25), p=0.319) or overall survival (D91.9%, I91.2% - HR: 0.90 (95%-CI:0.56-1.47), p=0.690). IPCW modelling results will be presented at the meeting.The overall rate of pleural effusion over 5 years in the dasatinib arm was 36.0% with a higher incidence in older patients. 13 patients developed their first pleural effusion after 3 years on study. Conclusions. In SPIRIT 2 we observed a higher molecular and cytogenetic response rate and also a higher pleural effusion rate with dasatinib but a higher treatment failure rate with imatinib often because investigators were concerned about sub-optimal PCR responses. More imatinib-treated patients proceeded to transplant. There were no statistically significant differences in event free survival (the primary endpoint) or overall survival. Imatinib remains a highly effective first line therapy though subgroup analyses are planned to explore whether dasatinib may have advantages in particular clinical scenarios. Disclosures O'Brien: Bristol Myers Squibb: Research Funding; CTI: Other: Chair of Independent Data Monitoring Committee; National Institute for Health and Care Excellence (NICE): Other: Chair of Technology Appraisal Committee. Osborne:Servier: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; MSD: Honoraria; Roche: Honoraria; Novartis: Honoraria. Bell-Gorrod:Bristol-Myers Squibb: Consultancy; Merck EDM Serono: Consultancy; PharmaMar: Consultancy; Novartis: Consultancy; GlaxoSmithKline: Consultancy. Latimer:Pfizer: Consultancy; BMS: Consultancy; Merck: Consultancy; Astra Zeneca: Consultancy; Bluebirdbio: Consultancy; Janssen: Consultancy. Apperley:Incyte: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Byrne:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Pocock:Kent & Canterbury Hospital: Employment. Copland:Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Clark:Ariad/Incyte: Consultancy; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

scholarly journals Ponatinib and Chemotherapy in Young Adults with De Novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Results of Ponalfil Clinical Trial after Completion of Recruitment

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Josep-Maria Ribera ◽  
Olga García ◽  
Pau Montesinos ◽  
Pilar Martinez ◽  
Jordi Esteve ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Molecular Response ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Central Artery

Background and objective. The combination of tyrosine kinase inhibitors (TKI) and chemotherapy (intensive, attenuated or minimal) has improved the prognosis of patients (pts) with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). The combination of HyperCVAD and ponatinib has improved the molecular response and survival compared with other combinations of chemotherapy with first or second generation TKI (Jabbour E, et al, Lancet Haematol. 2018; 5:e618-e627). The Spanish PETHEMA group conducted the phase 2 PONALFIL trial, which incorporates ponatinib to the same induction and consolidation schedule of the ALL Ph08 trial (Ribera JM et al. Cancer 2019;125:2810-2817) The results of this trial after completed recruitment are herein reported. Patients and method. The PONALFIL trial (NCT02776605) combined ponatinib (30 mg/d) and induction chemotherapy (vincristine, daunorubicin and prednisone) followed by consolidation (high-dose methotrexate, ARA-C, mercaptopurine, etoposide) and allogeneic HSCT. TKI use as maintenance was only scheduled for pts with persistence or reappearance of MRD. By July 2020 the 30 scheduled pts were recruited. The response to therapy (complete morphological [CR], molecular [complete, CMR or major, MMR] after induction and before allogeneic HSCT) (assessed by centralized BCR-ABL/ABL ratio),event-free survival (EFS), overall survival [OS]) and toxicity are herein analyzed. Results. Median age was 50 (20-59) years and 14/30 pts were female. One pt showed CNS involvement at diagnosis. ECOG score at diagnosis was &lt;2 in 86% of pts. Median of WBC count was 6.4 (0.6-359.3) x109/L, Hb 90 (63-145) g/L, platelets 38 (11-206) x109/L. The immunologic phenotype was common in 26 cases, with molecular isoform p190 in 20 patients (67%), p210 in 9 (30%) and p230 in 1 (3%). CR was attained 26/26 patients (100%) (4 are still on induction therapy), with CMR in 11/26 cases (42%), MMR in 6/26 (23%) and no molecular response in 9/26 (35%)).Two patients withdrew the trial (thrombosis of the central retina artery and severe intestinal infection, one case each). Consolidation was given to 24 patients, 2/24 are receiving consolidation and 22 patients received allogeneic HSCT (14 in CMR, 6 in MMR, 2 without molecular response). No relapses before HSCT were detected. No transplant-related mortality was observed to date, but 1 patient withdrew the trial by severe GVHD. Ponatinib was given after HSCT in 4 pts due to loss of molecular response. Three pts relapsed after HSCT, one of them after documented loss of molecular response. All pts are alive (median follow-up of 4.5 months, range 0.5-26.2.2). The EFS probability at 30 months was 91% (79%, 100%) (Figure 1). One hundred and two adverse events (AE) have been registered in 20 patients, 25 of whom were severe (SAE) and occurred in 14 patients, prompting to withdrawn of the trial in 3 (thrombosis of the central artery of the retina, severe bowel infection, grade IV aGVHD, one case each). The most frequent AE were hematologic (26%), gastrointestinal (15%), infections (10%), hepatic (8%) and cutaneous (5%). Cardiovascular events occurred in 2 patients (angor pectoris and thrombosis of central artery of the retina, one case each). Conclusions. The preliminary results of the PONALFIL trial after recruitment completed show a high short-term antileukemic efficacy with acceptable toxicity profile. Supported in part by grant 2017 SGR288 (GRC) Generalitat de Catalunya and "La Caixa" Foundation. Figure 1. Event free survival (EFS) of the whole series. Figure 1 Disclosures Ribera: Pfizer, Amgen, Ariad, Novartis: Consultancy, Speakers Bureau; Pfizer, Amgen: Research Funding. Martinez-Lopez:Incyte: Consultancy, Research Funding; Novartis: Consultancy; BMS: Consultancy, Research Funding; Janssen-cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria. Garcia-Sanz:Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Gilead: Honoraria, Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Pharmacyclics: Honoraria; Takeda: Consultancy, Research Funding.

Maintaining Imatinib ≥600 Mg Daily in the First 12 Months of Chronic Phase CML Treatment Is Associated with Superior Event-Free Survival at 5 Years.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1125-1125 ◽  
Author(s):  
Michael P Osborn ◽  
Susan Branford ◽  
Deborah L White ◽  
John F Seymour ◽  
Ruth Columbus ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Event Rates

Abstract Abstract 1125 Poster Board I-147 The Australasian Leukaemia and Lymphoma Group conducted a trial (TIDEL I) in 103 patients with newly diagnosed chronic phase CML, using imatinib 600 mg/day with dose escalation to 800 mg/day for suboptimal response. This was defined as failure to achieve (1) complete haematological response (CHR) at 3 months, (2) major cytogenetic response (MCR) at 6 months, (3) complete cytogenetic response (CCR) or molecular equivalent at 9 months, or (4) less than 0.01% (IS) BCR-ABL by RQ-PCR at 12 months. Here we report the outcomes with all surviving patients having been treated for at least 60 months. We aimed to determine whether the patient outcome at 60 months was predicted by the molecular response within the first 18 months of imatinib therapy. The outcomes for patients maintaining a dose of imatinib of ≥600 mg/day in the first 12 months was compared to those who were on a reduced dose for at least part of this time. Event-free survival (EFS) was defined as death from any cause, accelerated phase/blast crisis (AP/BC), and loss of CHR, MCR or CCR. The 103 patients included 66 males and 37 females with a median (±SD) age of 49 (±14) years. All patients had an ECOG performance status of 0-2 at enrolment. The 5-year EFS was 71%, transformation (AP/BC) free survival (TFS) was 95%, and overall survival was 87%. Of the 14 patients who died, 3 died in blast crisis, 2 from transplant-related complications, 8 from CML-unrelated causes, and the cause of death of 1 patient was unavailable. The annual rates of progression to AP/BC over 5 years were 3%, 1%, 0%, 1%, and 0%, while annual event rates were 13%, 8%, 8%, 1%, and 4%. CCR was achieved by 89% of patients by 60 months, while 72% achieved a major molecular response (MMR) by this time. In the first 12 months of treatment, 55% of patients maintained an imatinib dose of ≥600 mg/day (mean ±SD dose = 604 ±10 mg/day), while 45% were on <600 mg/day for at least part of this time (mean ±SD dose = 511 ±100 mg/day). EFS at 60 months was significantly higher in patients taking ≥600 mg/day compared with those who had been dose-reduced to <600 mg/day (89% vs 56%, P<0.001). Annual event rates for the ≥600 mg/day group were 6%, 2%, 2%, 0%, and 2%, while annual event rates for those on <600 mg/day were 14%, 16%, 16%, 8%, and 4%. By 60 months, 96% of patients who had been on ≥600 mg/day within the first 12 months had achieved CCR, while only 80% of those who had been on <600 mg/day had achieved this milestone (P<0.001). Log rank analysis of the achievement of MMR was also significant (P=0.03). Overall survival and TFS after 12 months were both similar between the dosing groups. There was no difference between the dosing groups' median age (50 vs 48 years, P=0.36) or Sokal score (1.04 vs 0.94, P=0.33) that may otherwise account for these results. The outcome was also determined for all patients dependent on the BCR-ABL levels at various assessment timepoints. Patients with a BCR-ABL level of <10% (IS) at 6 months (n=92) had an EFS of 78% at 60 months, while all of those with a level >10% (IS) (n=8) had an event (P<0.001). Patients with a level of ≤1% (IS) at 12 months (equivalent to CCR) (n=81) had an EFS of 75% compared with 25% (n=13) for those with levels >1% (IS) (P<0.001). At 18 months, a level ≤0.1% (IS) (n=58) conferred an EFS of 88%, while those who had failed to attain this depth of response (n=30) had an EFS of 60%. There was a significant difference in EFS between those who had achieved an MMR at 18 months and those who had achieved a CCR, but no MMR (88% vs 67%, P=0.03). In conclusion, our data suggest that patients maintaining a dose of ≥600mg in the first 12 months of imatinib therapy are more likely to achieve CCR and MMR, and superior EFS compared to those with a lower dose. This study also confirms that achieving an MMR by 18 months is associated with improved EFS. This emphasises the value of achieving a molecular response early in the treatment course, as well as adding weight to the evidence supporting the role of molecular monitoring in CML. Disclosures Branford: Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. White:Novartis and Britol-Myers Squibb: Research Funding. Seymour:Bayer Schering: Consultancy, Membership on an entity's Board of Directors or advisory committees, Travel grants; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel Grants. Catalano:Roche: Honoraria, Research Funding, Travel grants. Mills:Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hughes:Bristol-Myers Squibb: Advisor, Honoraria, Research Funding; Novartis: Advisor, Honoraria, Research Funding.

scholarly journals Outcomes of Plasma Cell Leukemia Patients in the Era of Next-Generation Novel Agents: A Single-Center Retrospective Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Alex Ge ◽  
Chiung-Yu Huang ◽  
Thomas Martin ◽  
Jeffrey L. Wolf ◽  
Nina Shah ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Next Generation ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Introduction Primary plasma cell leukemia (pPCL) is a rare and aggressive disease comprising 1-5% of all plasma cell dyscrasias. Although historically pPCL has been defined by circulating plasma cells (CPCs) ≥ 20% and 2.0 × 109/L, many series require only one of these two criteria for diagnosis. Over time there has been a pressing need to change the definition further in order to capture patients at an earlier stage of the disease. Recent studies have shown that multiple myeloma (MM) patients who have CPCs ≥ 5% but &lt; 20% at diagnosis have similarly poor outcomes. These thresholds for defining pPCL have not been studied in the current era of novel agents. While bortezomib-based regimens have been shown to extend pPCL patient survival, studies with next-generation agents such as carfilzomib (CFZ), pomalidomide, and daratumumab (DARA) are still scarce. Methods We performed a single-center, retrospective study of patients who at diagnosis had pPCL (defined as CPCs ≥ 20% or 2.0 × 109/L) or had MM with &lt; 20% CPCs (MM-CPC). Patients were treated at our institution between 1/1/2000-7/17/2020. Overall response rates were determined according to International Myeloma Working Group criteria. Overall survival (OS) was defined as the length of time between initiation of first line therapy and death. Progression-free survival (PFS) was defined as the length of time between initiation of first line therapy and first progression. OS and PFS were compared using log-rank tests. Results Of the 54 patients identified, 38 had pPCL and 16 had MM-CPC. The median age at diagnosis of the pPCL and MM-CPC groups were 59.2 (range 43-94) and 59.8 years (range 29-79), respectively, with a similar percentage of females, 47.4% vs. 37.5%. Both groups were similarly distributed by year of diagnosis; 76.3% and 62.5% of pPCL and MM-CPC patients were diagnosed between 2012-2020, respectively. The pPCL cohort had median CPCs of 40% (15-98) while the MM-CPC cohort had median CPCs of 4% (1-15). Median CPCs at diagnosis was 3.36 (0.44-179) × 109/L in the pPCL group compared to 0.33 (0.04-1.79) × 109/L in the MM-CPC group. Most patients for both groups were ISS stage III at diagnosis (57.9% in pPCL cohort, 56.2% in MM-CPC cohort). R-ISS assessment was not feasible due to missing data. A greater proportion of patients in the pPCL group (44.7%) had complex cytogenetics at diagnosis compared to the MM-CPC group (25.0%). All patients were exposed to at least one novel agent over the entire disease course. Of these patients, 50 (92.6%) were exposed to bortezomib, 45 (83.3%) to lenalidomide, 33 (61.1%) to CFZ, 22 (40.7%) to DARA, 13 (24.1%) to pomalidomide, and 4 (7.4%) to venetoclax. Twenty-four patients (44.4%) received an autologous stem cell transplant (ASCT). At the best response to treatment, 76.7%, 62.8% and 37.9% of patients achieved a partial response or greater to first, second and third line therapy, respectively. The median OS of the pPCL and MM-CPC groups was 34.5 and 35.5 months (p = 0.97) (Figure 1A), while the median PFS was 13.9 and 10.9 months (p = 0.52) (Figure 1B), respectively. The median follow-up was 28.1 months. No differences were observed for patients with CPCs &lt; 20% compared to patients with CPCs ≥ 20% (p = 0.98). There was trend towards a better survival for patients with CPCs &lt; 2 × 109/L compared to CPCs ≥ 2 × 109/L (p = 0.35). Since we did not observe any meaningful difference in OS or PFS between the pPCL and MM-CPC groups, we combined these groups for further survival analysis. Patients exposed to either DARA or CFZ (n = 37) had a median OS of 59.2 months, while patients exposed to neither drug (n = 17) had a median OS of 11.7 months (p = 0.02) (Figure 1C). ASCT was associated with a prolonged median OS (66.8 months vs. 17.2 months, p = 0.0001) (Figure 1D), while a complex karyotype at diagnosis was associated with a poorer median OS (17.4 months vs. 66.8 months, p = 0.01). Conclusions In the era of next-generation novel agents, overall and progression-free survival of pPCL and MM-CPC patients are similar. Patients exposed to DARA or CFZ have an improved survival compared to those who did not receive these drugs. ASCT is also associated with a superior survival over those who did not receive a transplant. Further studies are needed to evaluate the efficacy of these next-generation drugs in this patient population. Disclosures Martin: Janssen: Research Funding; Seattle Genetics: Research Funding; AMGEN: Research Funding; GSK: Consultancy; Sanofi: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Wong:Sanofi: Membership on an entity's Board of Directors or advisory committees; Fortis: Research Funding; Roche: Research Funding; Janssen: Research Funding; Amgen: Consultancy; GSK: Research Funding; Bristol Myers Squibb: Research Funding.

scholarly journals Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5880-5880
Author(s):  
Nathan H Fowler ◽  
Yanni Hao ◽  
Stephen Lim ◽  
Guifang Chen ◽  
Frank Li ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

scholarly journals Optimizing Deep Response Assessment for AL Amyloidosis Using Involved Free Light Chain Level at End of Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3227-3227
Author(s):  
Eli Muchtar ◽  
Angela Dispenzieri ◽  
Nelson Leung ◽  
Francis K. Buadi ◽  
David Dingli ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
Response Assessment ◽  
Al Amyloidosis ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Organ Response

Abstract Introduction: Light chain burden in light chain (AL) amyloidosis is often low, making accurate response assessment challenging. Methods: AL amyloidosis patients achieving very good partial or complete response to first line therapy and had serial sFLC studies during and after completion of therapy were included (n=396). Involved free light chain (iFLC), difference in involved-to-uninvolved free light chains (dFLC) and sFLC ratio (sFLCR) were assessed at the end of first line therapy and at nadir iFLC. Survival analysis was done using the Kaplan-Meier method. Hematological progression-free survival (hemPFS) was defined as the time from diagnosis until hematological progression or death, where patients known to be alive and progression-free at the end of follow-up were censored. Hematological progression was defined according to consensus criteria or upon initiation of second line therapy, whichever came first. Results: The median iFLC and dFLC at the end of therapy was 1.7 mg/dL and 0.5 mg/dL, respectively. sFLCR normalization occurred in 70% of patients. iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL were associated with a longer hemPFS compared to their counterparts (Figure). Only iFLC ≤2 mg/dL was associated with a significantly longer overall survival (Figure). sFLCR normalization did not predict hemPFS or overall survival. Organ response was predicted by iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL (Table), with best discrimination seen with iFLC ≤2 mg/dL. Organ response was not predicted by sFLC normalization (Table). The median nadir iFLC was 1.4 mg/dL and was reached 3.9 months from the end of therapy, longer in transplanted patients compared to patients treated with non-transplant regimens (7.3 vs 1.8 months, respectively; P<0.001). iFLC ≤2 mg/dL at the completion of therapy and nadir iFLC reached >12 months from the end of therapy were favorable predictors of hemPFS/OS in a multivariate analysis. Conclusion: iFLC at the end of first line therapy better predicts for organ response and survival than dFLC among deep responders. Normalization of sFLCR does not predict for organ response or survival and should not be used as measure of therapeutic efficacy. Figure. Figure. Disclosures Dispenzieri: Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding. Kapoor:Celgene: Research Funding; Takeda: Research Funding. Russell:Vyriad: Equity Ownership. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gertz:Alnylam: Honoraria; celgene: Consultancy; Ionis: Honoraria; Abbvie: Consultancy; annexon: Consultancy; janssen: Consultancy; spectrum: Consultancy, Honoraria; Research to Practice: Consultancy; Medscape: Consultancy; Apellis: Consultancy; Teva: Consultancy; Amgen: Consultancy; Prothena: Honoraria; Physicians Education Resource: Consultancy.

scholarly journals Functional Cure, Defined As PFS of More Than 7 Years, Is Achieved in 9% of Myeloma Patients in the Era of Conventional Chemotherapy and of First-Generation Novel Anti-Myeloma Agents; A Single-Center Experience over 20-Year Period

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1968-1968
Author(s):  
Evangelos Terpos ◽  
Maria Roussou ◽  
Ioannis Ntanasis-Stathopoulos ◽  
Nikolaos Kanellias ◽  
Despina Fotiou ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
First Generation ◽  
Steering Committee ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Travel Grant

Abstract Advances in the management of multiple myeloma (MM) led to a significant prolongation of overall survival (OS), mainly of the younger patients; almost 10% of them experience more than 10-year OS. Although long progression-free survival (PFS) correlates with extended OS, there is very limited information for the characteristics of patients who manage to be progression-free for a long period after first-line therapy. The aim of this analysis was to evaluate the characteristics of patients who achieved at least 7-year of PFS after frontline therapy and compare them with those of all other patients who were treated in a single center during the same time period. Between January 1994 and December 2010, 406 consecutive newly diagnosed MM patients received first line therapy in the Department of Clinical Therapeutics (Athens, Greece). All patients had symptomatic disease, based on the IMWG criteria of that period (at least one CRAB symptom to start anti-myeloma therapy). Thirty-six (8.8%; 23M/13F) patients achieved a PFS of at least 7 years (long PFS group) after frontline treatment. The median PFS of these 36 patients is 10 years, while the other patients had a median PFS of 22 months. Long PFS patients were younger (median age 56 vs 68 years; p<0.001), had bigger body surface area (median: 1.85 m2 vs. 1.76 m2; p=0.013) and lower ECOG performance status (score 0-1: 71% vs 52%; p=0.014) compared to all others. Long PFS patients had higher hemoglobin (11.4 g/dl vs 10.2 g/dl; p=0.001), higher platelet count (278 vs 224 x109/l; p<0.001) and higher creatinine clearance (CrCl, based on the MDRD formula: 88 vs 67 ml/min; p<0.001; no patient in the long PFS group presented with CrCl <45 ml/min at diagnosis). There was no difference between the two groups regarding percentage of patients with high LDH, presence of osteolysis, type of myeloma (IgG vs IgA vs others), levels of serum and/or urine M-protein, and percentage of plasma cell infiltration in the bone marrow. However, more patients in the long PFS group had ISS-1 or ISS-2 disease (86% vs 61%; p=0.002) and normal pattern of marrow infiltration in the MRI of the spine and pelvis (24% vs 15%; p=0.035). Regarding chromosome abnormalities at diagnosis, no patient in the long PFS group had high-risk cytogenetics (defined as presence of del17p, t(4;14) or t(14;16) vs 32% in all other patients. All patients received either conventional chemotherapy (CC) or first-generation novel anti-myeloma agent (bortezomib (B), thalidomide (T) or lenalidomide (R)-based regimens as frontline therapy. There was no difference between the two groups regarding CC versus novel agent-based induction treatment. Out of 36 long-term PFS patients, 11 (30%) received CC, 8 (22%) B-based, 8 (22%) RD, 6 (17%) T-based, and 3 (8%) VTD; 10 (28%) patients received first-line therapy participating in a clinical trial. Long PFS patients had received more often autologous stem cell transplantation (ASCT, 61% vs 23%; p=0.001) as part of first line therapy; therefore, more long PFS patients had also received consolidation and/or maintenance (50% vs 15%; p=0.001). Higher proportion of patients achieved at least VGPR (74% vs 41%) or at least CR (32% vs 18%) in the long PFS group. We performed next generation flow cytometry in 23 patients of the long PFS group to evaluate minimal residual disease (MRD) and 14 (61%) of them were MRD (-) at the level of the 10-6. The probability of achieving long PFS (≥7 years) for patients who managed to be progression-free at 2, 3 and 4 years was 11.6%, 13.2% and 15.3%, respectively. In the multivariate analysis, only younger age was associated with probability for long PFS (p<0.001). The median OS of the whole group of patients was 5 years; in the long-PFS group median OS has not been reached yet while in all other patients the median OS was 4.3 years. In conclusion, our study in an unselected group of patients, the majority of whom did not participate in clinical trials, showed that 9% of patients with newly diagnosed myeloma experience prolonged PFS of more than 7 years (median: 10 years) even in the era of CC or first-generation novel agents. These patients have low risk disease, mainly of ISS-1 or -2, no high-risk cytogenetics, no or mild renal impairment, and achieve deep responses after ASCT. These patients may be considered as "functionally" cured. The incorporation of novel treatment approaches may lead to a significant improvement in the probability of achievement of this "functionally" cured status. Disclosures Terpos: Novartis: Consultancy; BMS: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding. Kastritis:Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria.

The Survival Outcome of the Patients with Relapsed/Refractory Anaplastic Large-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2738-2738 ◽  
Author(s):  
Dai Chihara ◽  
Michelle A. Fanale ◽  
Mansoor Noorani ◽  
Jason R Westin ◽  
Loretta Nastoupil ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Survival Outcome ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Large Cell Lymphoma

Abstract Purpose: We assessed the survival outcome of patients with anaplastic large cell lymphoma (ALCL) who experienced disease progression or relapse after first line and subsequent therapy. We sought to evaluate the impact of brentuximab vedotin (BV), and survival outcome of patients with ALCL who experienced progression after BV. Patients and Methods: A total of 176 patients (74 ALK+, 102 ALK-) initially diagnosed between 1999 and 2014 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) after the progression/relapse following first-line chemotherapy (PFS1 and OS1), after first salvage therapy (PFS2 and OS2) and after second salvage therapy (PFS3 and OS3) were calculated. Outcome was separately analyzed according to the ALK status focusing on the use of BV. Results: The median age of the patients was 50 (range: 18-89). With a median follow up of 64 months, 111 patients (38 ALK+, 73 ALK-) experienced progression/relapse after the first-line therapy, of which 4 ALK- patients were post upfront stem cell transplant (SCT). Thirty and 15 patients eventually underwent autologous and allogeneic SCT after salvage chemotherapy, respectively. The median PFS1 and OS1 in patients with ALK+ALCL and ALK-ALCL were 8.4 and 28.5 months, and 13.1 and 47.7 months, respectively. In patients with ALK+ALCL, the median PFS1, PFS2 and PFS3 were 53.6, 5.2 and 2.3 months, respectively. The median OS1, OS2 and OS3 were not reached, 47.3 and 6.1 months, respectively. In patients with ALK-ALCL, the median PFS1, PFS2 and PFS3 were 12.9, 3.0 and 2.0 months, respectively. The median OS1, OS2 and OS3 were 54.3, 10.8 and 5.8 months, respectively. Interestingly, there were no significant difference in PFS2 between ALK+ALCL and ALK-ALCL. However, OS2 was significantly longer in patients with ALK+ALCL, suggesting possibly continued chemosensitivity of recurrent ALK+ALCL. A total of 30 patients received BV in 1st salvage (15 patients) and after 2nd salvage (15 patients).The use of BV at 1st salvage was associated with significantly longer PFS2 and OS2 both in patients with ALK-ALCL but not with ALK+ALCL likely due to small number of cases. Mutivariate analysis adjusting baseline PIT risk factors and the duration of the response to first line therapy revealed that use of BV (at any point in the salvage setting) is significantly associated with longer OS2 (HR: 0.43, 95%CI: 0.23-0.80). Overall, 12 patients experienced relapse/progression after BV treatment. The median OS after BV failure was 1.4 months (95%CI: 0.5-9.5 months) (Figure). Summary: Survival outcome for relapsed/refractory patients with ALK+ and ALK- patients is improved with BV. However, survival outcome after BV failure is very poor. A new treatment strategies to consolidate or maintain the response after BV and to develop more safe and better therapeutic options are needed. Figure 1. Figure 1. Disclosures Fanale: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Westin:Spectrum: Research Funding. Nastoupil:Celgene: Honoraria; Genentech: Honoraria; AbbVie: Research Funding; Janssen: Research Funding; TG Therapeutics: Research Funding. Wang:Celgene: Research Funding.

Patterns of Care for Patients with Chronic Lymphocytic Leukemia (CLL): The Connect® CLL Disease Registry

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2864-2864
Author(s):  
Jeff Sharman ◽  
Christopher R Flowers ◽  
Mark Weiss ◽  
David Grinblatt ◽  
Charles Farber ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Age Groups ◽  
Age Group ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Ecog Ps ◽  
Group 1

Abstract Abstract 2864 Introduction: Clinical trials have illuminated a number of unique treatment strategies for patients with CLL. The impact of these strategies on routine practice remains unknown as trial participants may not reflect the same population encountered outside of a clinical trial setting. Many questions remain regarding the sequencing of therapies based on age and performance status. By characterizing current patterns of care; patients, treating physicians, and regulatory agencies will be able to understand the current landscape of CLL treatment. The Connect® CLL registry was designed to report the natural history and real world management of patients receiving therapy for CLL. In this first report, we characterize the therapeutic approaches used for the treatment of patients with CLL of different age groups (i.e. < 65 years, 65–75 years, and ≥ 75 years) and with an ECOG PS status score of 0 compared to 1 or greater. Methods: Connect® CLL is a prospective, longitudinal, observational, multi-center registry conducted in community and academic research centers in the United States. At present, 237 sites are actively participating with a projected study enrollment of 1500 patients. Eligible patients are to be enrolled within 2 months of being initiated on any line of therapy; whether initial therapy or salvage therapy. Each patient will be followed for up to 60 months. Clinical data, physician choices, patient-reported health-related quality of life, response and survival are to be collected approximately every 3 months during participation. Results: A total of 607 patients have been enrolled (4% from academic sites) with a median age of 70 years. 198 were < 65 years old (age group 1), 187 were between 65–75 years old (age group 2), and 222 were ≥ 75 years old (age group 3). ECOG status varied across the three age groups, with an ECOG status score of ≥ 1 for 39%, 52%, and 70% of patients respectively. Treatment patterns varied across the age groups and by ECOG status in the 496 patients reporting therapies. The most commonly recorded first-line regimens independent of age included fludarabine (F) cyclophosphamide (C) and rituximab (R) (33%), bendamustine (B) +/− R (19%), F +/− R (15%), or investigational therapy (15%). For second-line regimens and beyond, the most frequently recorded regimen was B +/− R (30%), FCR (23%), other F-based regimens (13%), or investigational therapy (8%). The use of FCR for first-line treatment decreased significantly with increasing age group, (45%, 32%, 20%, for age group 1, 2, 3 respectively, p=0.04, spearman correlation) while use of F +/− R remained level across the age groups (14%, 15%, 15%, respectively). Compared to age group 1, first-line therapy with B +/− R in age groups 2 and 3 (15%, 22%, 21%, respectively) was higher but did not achieve statistical significance. B +/− R represented the most common treatment for all age groups (37%, 26%, 29%, respectively) as second line therapy but did not vary by age (P=0.35). The use of chlorambucil was infrequent in all age groups, but was more common in age group 3 patients compared to the others (P=0.01), in both first-line (2%, 4%, 12%, respectively) and subsequent lines of therapy (0%, 1%, 8%, respectively). Treatment assignments did not vary by ECOG PS score for patients in age group 1. First-line therapy for patients with an ECOG PS score of 0 in age groups 2 and 3 consisted of FCR (32% and 15%, respectively), F +/− R (19% and 15%, respectively), B +/− R (16% and 15%, respectively), and alkylating agents (3% and 23%, respectively). Patients in age groups 2 and 3 with ECOG PS score ≥ 1 received B +/− R regimen (33% and 22%, respectively), FCR (23% and 21%, respectively), F +/− R (14% and 10%, respectively) and alkylating agents (7% and 9%, respectively) as first-line therapy. Further description and clarification on the various treatment regimens based on the three age groups and by ECOG PS score will be presented at the meeting. Conclusion: The Connect® CLL Registry is the largest prospective, multicenter registry in the United States evaluating management for patients with CLL. With the currently available data, we characterize the extent to which age and performance status are associated with treatment selection in both first-line and subsequent lines of therapy in routine practice. As enrollment increases and additional follow-up is completed, the data will provide more extensive and real world overview of the current treatment strategies used in CLL patients. Disclosures: Sharman: Celgene - consulting: Consultancy; Pharmacyclics: Honoraria; Calistoga: Honoraria; Portola pharmaceuticals: Consultancy. Flowers:Consultancy: Celgene, Prescription Solutions, Spectrum (future), Seattle Genetics, Millennium (future), Genentech (unpaid): Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Weiss:Celgene: Consultancy. Grinblatt:Celgene: Honoraria, Speakers Bureau. Kay:Genenetech, Celgene, Hospira,: Research Funding. Kipps:Igenica: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Abbot Industries: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; GSK: Research Funding; Gilead Sciences: Research Funding; Amgen: Research Funding. Lamanna:Celgene Corporation: Advisory board. Pashos:United BioSource Corporation: Research Funding. Flinn:Celgene: Research Funding. Kozloff:Celgene: Consultancy. Lerner:Celgene Connect: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene: Employment. Sullivan:Celgene: Employment. Street:Celgene: Employment. Keating:Celgene Connect: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Impact of Therapy Choice on Fatigue in Adults with Immune Thrombocytopenia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-20
Author(s):  
Jennifer Diraimo ◽  
Caroline Kruse ◽  
Michele P. Lambert ◽  
Alexandra Kruse
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Advisory Committees ◽  
Treatment History ◽  
First Line Therapy ◽  
Line Therapy

Background:Immune thrombocytopenia purpura (ITP) is an autoimmune bleeding disorder that is heterogeneous in presentation, disease course, treatment response, and impact on quality of life. Treatments often cause unpleasant side effects, and prolonged use can lead to tolerability issues and toxicity. Both disease symptoms and treatments available impact the health-related quality of life (HRQoL) among patients living with this rare condition. Here, we compare self-reported fatigue and its impact among adult ITP patients and determine whether these fatigue levels differ depending on treatment status. Methods: For this study, we used three of the five surveys from the PDSA Natural History Study Registry including; treatment history and two adult QoL surveys. As of June 2020, 357 adult patients completed the survey assessing treatment history. A total of 310 adult patients completed the adult QoL (part one) survey, and 301 adults completed the adult QoL (part two) survey. Patients were stratified by 1) no treatment received 2) treated in the past 3) on therapy within the last six months; patients currently on therapy were further stratified by first and second-line therapy. Results: Among the 357 completed surveys on treatment history, 11% (n=40) reported they have never received treatment for their ITP, while 46% (n=166) have in the past, and 43% (n=158) currently receive therapy (within the last six months). Among those currently on treatment, 82% receive monotherapy; 47 (26%) use a first-line therapy (corticosteroid, IVIG, or Anti-D), and 78 (43%) are using a second-line therapy (TPO-RA, rituximab, and other second-line options). Therapies reported include TPO-RA's (41%), corticosteroids (24%), IVIG (7%), rituximab (3%), SYK inhibitor (1%), antibiotics (4%), anti-D (1%), other second-line treatments (such as MMF, dapsone etc.), and "other" therapies including complementary treatments (14%). Overall, 93 (23%) reported having had a splenectomy at some point to manage their active ITP. When asked to reflect on general tiredness, 98% of patients (n=310) reported being tired overall, with 55% reporting feeling tired 'almost always/often' regardless of treatment group or type. Those who have never been treated reported they felt tired 94% of the time, and 55% reported feeling tired 'almost always/often'. Among those who are not currently on treatment (but have received therapy in past), 99% reported feeling tired overall, and 50% reported feeling tired 'almost always/often'. Respondents using a first line therapy reported feeling tired overall 100% of the time, and reported feeling tired 53% 'almost always/often'. Respondents using a second line therapy reported feeling tired 99% of the time, and indicated they were tired 59% 'almost always/often'. There were no significant differences between these treatment types and groups identified. When asked to reflect on fatigue levels over the last seven days, collectively, 86% reported fatigue, and 30% reported experiencing it 'very much/quite a bit'. Among those who had never been treated, 85% reported fatigue, and indicated they felt fatigue 27% of the time 'very much/quite a bit'. Respondents who were not receiving treatment reported feeling fatigue 84% of the time, of which 26% was experienced 'very much/quite a bit'. Among those receiving a first line therapy, 90% reported fatigue in the last seven days, and 34% reported they experienced this 'very much/quite a bit'. Those using a second line therapy reported feeling fatigue 91% of the time, and 29% reported this was 'very much/quite a bit'. There were no significant difference among these treatment types and groups. Conclusion: Reported fatigue and overall tiredness are high among those currently on treatment, not on treatment, and those who have never been treated for their ITP. We did not find that fatigue levels were related to treatment type or group, indicating that the underlying causes may not be platelet count, or disease severity, but rather a combination of factors associated with having an unpredictable chronic disease. The multi-faceted effects of ITP often take a significant toll on patients' quality of life. The registry continues to collect data with the intent of understanding the longitudinal impact of ITP and in future with more of a sample size we can learn if these trends continue. Disclosures Kruse: CSL Behring: Other: Grant paid to PDSA; UCB: Other: Grant and consultancy fee, all paid to PDSA; Rigel: Other: Grant paid to PDSA; Principia: Other: Grant paid to PDSA; Pfizer: Other: Grant and consultancy fee, all paid to PDSA; Argenx: Other: Grant paid to PDSA; Amgen: Other: Grant and honorarium, all paid to PDSA; Novartis: Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work. Lambert:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Consultancy; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; Octapharma: Consultancy, Research Funding; Bayer: Consultancy; Argenix: Consultancy; ClinGen: Honoraria; Platelet Disorder Support Association (PDSA): Consultancy; 22qSociety: Consultancy; ITP Australia: Consultancy; CdLS Foundation: Consultancy; RDMD ITP study: Consultancy; Sysmex: Research Funding; AstraZeneca: Research Funding.

Variation in Health-Related Quality of Life by Line of Therapy of Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3926-3926 ◽  
Author(s):  
Neil E. Kay ◽  
Christopher R. Flowers ◽  
Mark Weiss ◽  
Nicole Lamanna ◽  
Ian W. Flinn ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Advisory Committees ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
Line Therapy ◽  
Related Quality ◽  
Line Of Therapy

Abstract Abstract 3926 Introduction. Chronic lymphocytic leukemia (CLL) patients will have significant variation in signs and symptoms at initial presentation and across lines of therapy, with concomitant effect on patient health-related quality of life (HRQOL). HRQOL and other patient-reported outcomes, together with clinical outcomes, provide a more complete perspective on the burden of disease and facilitate a broader view of the impact of treatment regimens. This analysis evaluates whether the HRQOL of patients with CLL in the United States (US) varies at the time the patients are about to embark on various lines of therapy, and offers a baseline report from which subsequent longitudinal analysis post-treatment will be possible. Methods. Clinical and HRQOL data were collected in Connect®CLL, a prospective observational registry initiated in March 2010 involving centers in the US. Physicians provided data on the demographics and clinical characteristics of patients receiving therapy. HRQOL was self-reported by patients at enrollment using the Brief Fatigue Inventory (BFI, a symptom assessment tool), the EQ-5D (a non-disease-specific HRQOL instrument), and the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu, a leukemia-specific HRQOL instrument). We characterized patients who had initial (First Line), second (Second Line) or subsequent (Higher Line) treatment regimens prior to initiation of regimens. Reported mean overall and/or domain-specific BFI, EQ-5D and FACT-Leu scores were analyzed by line of therapy. Statistical significance of score differences among sub-cohorts was ascertained by ANOVA using SAS 9.1. Results. Evaluable data were reported on 1005 patients, enrolled from 161 centers (93% community, 7% academic). Patients were predominantly male (62%) and white (89%) with mean age at 69 (standard deviation [SD] 11) years. HRQOL scores by line of therapy are presented: The total FACT-Leu and FACT-G results, and the total EQ-5D Index and Visual Analogue Scale (VAS) results, consistently suggest that patients initiating first line therapy have somewhat better HRQOL compared with those initiating subsequent lines of therapy. FACT-Leu total scores of patients initiating first line therapy were associated with better physical and leukemia-specific considerations, and the EQ-5D total score was associated with better mobility and pain/discomfort. Conclusions. Initial results from the Connect® CLL Registry indicate that HRQOL prior to treatment is better among patients initiating first line therapy compared to patients initiating later lines of treatment. Future analyses should be conducted to determine what clinical or other factors may be associated with the HRQOL deterioration in patients initiating subsequent lines of therapy, so as to inform clinician decision making. Also, subsequent longitudinal analyses should be undertaken to determine how HRQOL might be affected by the different lines of therapy and the specific treatment regimens, as well as by their initial HRQOL and other patient factors. Disclosures: Kay: Celgene: Research Funding. Flowers:Celgene: Consultancy; Prescription Solutions: Consultancy; Seattle Genetics: Consultancy; Millennium: Research Funding, Unpaid consultancy, Unpaid consultancy Other; Genentech: Unpaid consultancy, Unpaid consultancy Other; Gilead: Research Funding; Spectrum: Research Funding; Janssen lymphoma research foundation: Membership on an entity's Board of Directors or advisory committees. Weiss:Celgene: Consultancy. Lamanna:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Flinn:Celgene: Research Funding. Grinblatt:Celgene: Honoraria, Speakers Bureau. Kipps:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kozloff:Celgene: Consultancy. Lerner:Celgene Connect: Membership on an entity's Board of Directors or advisory committees. Sharman:Celgene: Consultancy; Pharmacyclics: Honoraria; Calistoga: Honoraria; Portola pharmaceuticals: Consultancy. Khan:Celgene Corporation: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment. Sullivan:Celgene: Employment. Pashos:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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