Analysis of an Online Decision Support Tool for Chronic Lymphocytic Leukemia: Disparities in Treatment Selection Between Experts and Community Practitioners

Abstract Background. Rapid advances in clinical discovery and availability of new treatment options have increased the complexity of treatment decisions for patients with CLL. Guidelines list multiple agents and combinations as recommended therapeutic options for CLL but often do not provide specific treatment recommendations for individual patients. We developed an online treatment decision tool that provides treatment recommendations from CLL experts for specific patient cases. We hypothesized that these individualized recommendations from recognized experts would affect treatment plans. Here we report on an analysis of data entered into this CLL decision support tool, including variance between intended treatment of tool users and the recommendations made by the experts and the impact of the tool on subsequent therapy decisions. Methods. In December 2015, 5 experts provided treatment recommendations for 1380 case variations based on key factors that guide treatment choice. Expert-selected factors for newly diagnosed CLL included age, fitness (based on ECOG PS, CIRS, and renal function), and cytogenetic abnormalities (del[17p], del[11q], or other). Additional variables for patients with relapsed/refractory (R/R) disease after first-line treatment included previous treatment, response duration, and burden of comorbidities. To use the tool, drop-down menus allowed users to select from choices for each variable and their intended treatment for that patient. The corresponding treatment selection from 5 experts was then displayed and users were asked about the tool's impact on their planned treatment. Results. An analysis of 883 patient scenarios (67% treatment naive and 33% with R/R CLL) entered into the tool from February 2016 through July 2016 found substantial variation between the intended therapy choice among tool users and the recommendations from the experts.For example, in every patient case with del(17p), all 5 of the experts recommended ibrutinib as first-line therapy whereas only 49% of tool users planned to use ibrutinib for these patients. Of those users whose intended first-line therapy for del(17p) CLL did not match the experts' recommendation, 54% indicated that this tool would change their original treatment plan and 17% indicated a barrier to implementing this treatment. For either elderly or unfit patients without del(17p), 4 of 5 experts recommended obinutuzumab plus chlorambucil, but only 41% of tool users planned to use this regimen with 50% citing barriers to this treatment approach. For patients with del(17p) CLL and disease relapse or recurrence after chemoimmunotherapy, all 5 experts recommended ibrutinib for these cases with the exception of patients with a history of atrial fibrillation, anticoagulation, or difficult-to-control hypertension where 4 of 5 experts recommended idelalisib/rituximab. Again, the intended treatment plan of approximately 50% of tool users failed to match the experts' recommendation for these cases, and half of these users indicated that this tool would change their original treatment plan. At the time of tool development, all experts recommended either idelalisib/rituximab or clinical trial for patients with R/R CLL and del(17p) who previously received ibrutinib, but 61% of users indicated that they were unsure of the next appropriate treatment. All users who answered the impact question indicated that they now intended to use the expert-recommended treatment for these patients. For patients without del(17p) cytogenetics, treatment selection was more variable among experts and users and changed based on age, fitness, and previous therapy. For patients with del(11q) or other cytogenetics, approximately 20% of tool users were unsure of the appropriate treatment after progression on first-line therapy but 71% of those who answered the impact questions indicated that they remained unsure of their treatment approach despite viewing expert recommendations. Conclusions. Our analysis demonstrates that this interactive online therapy decision tool providing expert recommendations for specific case scenarios in CLL can support optimal decision making and change intended treatment for a majority of cases in which the planned therapy differed from the experts. Detailed comparisons of expert and user responses from the online tool will be presented. Disclosures Awan: Innate Pharma: Research Funding; Pharmacyclics: Consultancy; Novartis Oncology: Consultancy. Barrientos:AbbVie: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Consultancy, Research Funding. Coutre:AbbVie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding. Zelenetz:Gilead Sciences: Research Funding.

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Role of Neutrophil Lymphocyte Ratio [NLR] As a Biomarker of Frailty and Predictor of Survival Among Older Adults with Multiple Myeloma (MM)

Blood ◽

10.1182/blood-2020-143290 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-6

Author(s):

Smith Giri ◽

Susan Bal ◽

Kelly N. Godby ◽

Joshua Richman ◽

Adam J Olszewski ◽

...

Keyword(s):

Older Adults ◽

Overall Survival ◽

Research Funding ◽

First Line ◽

Targeted Interventions ◽

First Line Therapy ◽

Systems Research ◽

Line Therapy ◽

Race Ethnicity ◽

The Impact

Introduction: NLR combines a marker of inflammation (neutrophilia) and immune senescence (lymphopenia) to reflect aging related alterations in the immune systems. Prior studies have shown that NLR can serve as a marker of frailty and predict survival among older adults with solid tumors and lymphomas, its role among older adults with MM remains unclear. Methods: We used the Flatiron Health electronic health record-derived de-identified database to source older adults (age ≥60y) with incident MM diagnosed between 1/1/2011 and 2/1/2020. We limited our study cohort with known first line therapy and absolute neutrophil and lymphocyte count (cells//µL) up to 90 days before the start of treatment. We constructed a modified frailty index (Facon et al Leukemia 2020) at MM diagnosis combining age, comorbidity and ECOG performance status, captured within 90 days from the start of first line therapy categorizing patients into frail vs nonfrail. We examined the association between NLR (stratified into quartiles, Q1-Q4) and frailty using logistic regression model adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for age, sex, race/ethnicity, international staging system (ISS) stage, high-risk cytogenetics (HRCA; del17p, t4;14 or t14;16), and first-line therapy. Results: Of 2792 eligible patients, the median age at MM diagnosis was 73y (IQR: 67-78y), with 53% males and 61% non-Hispanic whites. Of these, 56% had IgG isotype, 22% ISS stage-III and 13% had HRCA. The median NLR was 2.29 (IQR: 1.5 to 3.59). Of the 1,743 evaluable for frailty, 1042 patients (59.8%) were frail. Overall, 45% received proteasome inhibitor (PI) + Immunomodulatory agent (Imid) based first line therapy and 19% received autologous stem cell transplantation. Patients in the highest NLR quartile were at a 2.1-fold higher odds of being frail (95% CI 1.52-2.86; p <0.001) when compared with those in the lowest NLR quartile (after adjusting for age, sex and race/ethnicity). NLR was poorly correlated with age (Pearson's r= 0.02). Patients in the highest NLR quartile had an inferior overall survival vs those in the lowest quartile (median OS/3y-OS in Q4 3.3y/53% vs 4.7y/69% in Q1; log-rank p <0.01). Similar results were seen when limiting to patients receiving first line PI & Imid triplet and PI or Imid based doublet regimens (Fig 1). In a multivariable analysis, patients in the highest NLR quartile had a 1.5 times increased hazards of death (95% CI 1.28-1.85, p <0.001) when compared with those in the lowest NLR quartile, after adjusting for potential confounders (Table 1). Conclusion: NLR is an easily available laboratory biomarker associated with frailty as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM and guide appropriate treatment selection and targeted interventions to prevent excess toxicities and improve outcomes. Table 1 Disclosures Giri: Pack Health: Research Funding; Carevive Systems: Research Funding; Carevive Systems: Honoraria. Olszewski:Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Costa:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Genentech: Consultancy.

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Oral Fludarabine and Intravenous Rituximab (FR) for Chronic Lymphocytic Leukemia (CLL): Long Term Outcomes and Secondary Malignancies in 673 Patients Treated in British Columbia (BC)

Blood ◽

10.1182/blood-2019-125189 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4300-4300

Author(s):

Elysha Vanderveer ◽

Steven J.T. Huang ◽

Helene Bruyere ◽

Tanya Gillan ◽

Charles H. Li ◽

...

Keyword(s):

Median Time ◽

Research Funding ◽

Secondary Malignancies ◽

Long Term Outcomes ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

The Impact

Background: Oral fludarabine and intravenous rituximab (FR) was the standard first-line therapy for CLL or small lymphocytic lymphoma (SLL) patients (pts) in BC from 2003-2015. Ibrutinib for relapsed/refractory (R/R) CLL was introduced and publicly funded in 2015. Our aim was to review long term outcomes of all CLL/SLL pts treated with FR in BC, including the impact of 2nd line therapy with ibrutinib versus chemoimmunotherapy and to report the risk of secondary malignancies in this population based cohort. Methods: The BC Provincial CLL Database was used to identify all CLL/SLL pts who received first-line FR from 2003-2017. The BC Cancer Registry was used to identify secondary malignancies occurring after FR. Primary outcomes were overall survival (OS) and treatment free survival (TFS), defined as start of FR to next-line therapy or death/last follow-up. Variables examined for impact on OS/TFS included age at FR, gender, primary diagnosis (CLL vs SLL), B symptoms, advanced stage (Rai stage 3-4 CLL, Ann Arbor 1-2 SLL), baseline hemoglobin, lymphocyte count, platelets, LDH and FISH abnormalities. All variables significant on univariate analyses (P<.1) were included in multivariate Cox proportional hazard regression models to identify significant predictors of OS/TFS. Results: 673 pts were identified as receiving FR as first-line therapy for CLL (86%) or SLL (14%). Median time from CLL/SLL diagnosis to FR was 2.5 years (y) (range 0.1-27.3). Median age at FR was 67 y (range 26-91) with 73% ≥ 60 y and 39% ≥ 70 y. Most pts were male (66.1%), had early stage disease (84.2%) with no B symptoms (89.7%) and normal LDH (81.1%). Of 411 pts with pre-treatment FISH testing, prevalence of FISH abnormalities were: 48.5% del13q, 25.7% trisomy 12, 12.9% del11q, 8.0% del17p. Median number of FR cycles was 6 (range 1-10). Median follow-up of living pts from FR was 6.4 y (range 0.2-12.7). 2 y and 5 y OS were 89.4% (95% CI: 86.8-91.6) and 73% (95% CI: 69.0-76.6) respectively; median OS 11.6 y (95% CI: 4.6-13.7 y). 2 y and 5 y TFS were 72% (95% CI: 68-75%) and 37% (95% CI: 33 - 41) respectively, median TFS 3.8 y (95% CI: 1.78-7.09). Those with del17p had significantly worse OS and TFS compared to those without (median OS 5.7 vs 13.7 y, P<.001; median TFS 1.4 vs 3.9 y, P<.001), Fig. 1. Multivariate analysis identified only del17p (HR 4.35, 95%CI: 2.10-9.01, P<.001) and age at FR (HR 1.04, 95% CI: 1.01-1.07, P=.007) as significant predictors of OS, and del17p (HR 4.3, 95% CI: 2.5-7.5, P<.001) as a significant predictor of TFS. During the follow up period, 351 pts (52%) went on to 2nd-line therapy: ibrutinib 87 (including 2 with BR and 1+R), cyclophosphamide-based (CVP/CHOP) +/- R 102, repeat FR 71, FCR 6, F alone 21, bendamustine +/-R 13, chlorambucil+/-R 38, steroids 3, R alone 3, alemtuzumab 2, other chemotherapy 3 and allotransplant 2. Median follow-up after 2nd-line therapy was 2.8 y (range 0.1-10.8). Median OS and TFS from 2nd-line treatment (TFS2) for ibrutinib (n=87) vs. for other treatments (n=264) was: OS not reached vs 5.3 y, P<.001; TFS2 not reached vs 1.2 y, P<.001. These significant differences persisted when analyses were restricted to those who received ibrutinib vs. chemoimmunotherapy (n=169): median OS not reached vs. 6.3 y (P=.002); median TFS not reached vs. 1.7 y (P<.001), Fig. 2. 2 y OS and TFS2 after ibrutinib were 91% (95% CI: 80-96%) and 78% (95% CI: 65-87%), respectively. A total of 202 malignancies were recorded after initiation of FR in 166 pts (24.7%), Table 1. The median time from FR to 2nd malignancy was 2.3 y (range 0.1-13.5). Richter's transformation (RT) occurred in 36 pts (5.3%) at median 1.9 y (range 0.1-13.2) from FR. Most frequent 2nd malignancies were: non-melanoma skin cancer (11.7%), lung (2.5%), colon (2.1%), other heme (1.9%), and prostate (1.8%). There were 4 cases of acute myeloid leukemia (AML), 2 of which received alkylator therapy after FR prior to AML diagnosis. Conclusions: In this large, homogeneous cohort of CLL/SLL pts treated with first-line FR, including nearly 40% of pts ≥ age 70, we demonstrate a short median TFS of 3.8 y; however, a long OS of 11.6 y. Rates of 2nd malignancies are low after this non-alkylator based chemoimmunotherapy regimen. Ibrutinib for R/R CLL/SLL after FR resulted in significantly improved survival over alternate therapy, with excellent 2 yr OS 91% and TFS 78%. These data demonstrate the efficacy of FR and the benefit of ibrutinib over chemoimmunotherapy as second-line therapy for CLL/SLL in the real-world. Disclosures Bruyere: Jenssen: Other: Travel Grant; Celgene: Honoraria. Villa:Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Scott:Celgene: Consultancy; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Connors:Takeda Pharmaceuticals: Honoraria; Seattle Genetics: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Sehn:TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria.

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Early Autologous Stem Cell Transplantation (autoSCT) May Overcome the Adverse Impact of Del 11q- in Poor-Risk Chronic Lymphocytic Leukemia (CLL): Results From the GCLLSG CLL3 Trial.

Blood ◽

10.1182/blood.v114.22.879.879 ◽

2009 ◽

Vol 114 (22) ◽

pp. 879-879 ◽

Cited By ~ 1

Author(s):

Peter Dreger ◽

Hartmut Döhner ◽

Hildegard Greinix ◽

Fabienne McClanahan ◽

Manfred Hensel ◽

...

Keyword(s):

Research Funding ◽

Hazard Ratio ◽

Lymphocytic Leukemia ◽

First Line ◽

Female Ratio ◽

Poor Risk ◽

First Line Therapy ◽

Line Therapy ◽

Mutational Status ◽

The Impact

Abstract Abstract 879 As previously reported, dose-escalated first-line therapy with autoSCT as conducted in the GCLLSG CLL3 protocol is a feasible and effective therapy option for younger patients with poor-risk CLL. Purpose of the present analysis was to study the impact of FISH karyotype according to the hierarchical model, and of IGHV mutational status on progression-free (PFS) and overall survival (OS) in this trial. Trial design and patients: The protocol comprised optional cytoreduction with CHOP, fludarabine, or FC; PBSC mobilization using the Dexa-BEAM regimen; and myeloablative therapy with TBI/CY followed by reinfusion of purged (CD34+) stem cells. Inclusion criteria were age <61 years, stage Binet B/C or poor-risk stage A as defined by short lymphocyte doubling time plus elevated TK, and one line of pretreatment or less. From December 1996 through September 2002, 216 patients were registered with the protocol. As 47 cases had to be excluded due to screening failure (n=21), withdrawn consent (n=19) or other reasons (n=7), 169 patients were eligible for the current analysis. Male to female ratio was 5:1 and the median age at diagnosis was 51 years (range 27-60). Results: SCT was performed in 131 patients (78%) at a median time of 17 months (range 4-159) after initial diagnosis, whereas 38 patients did not proceed to SCT due to mobilization failure (n=14), disease progression (n=4), early death (n=3), patients preference (n=6), or unknown reasons (n=11). At a median follow-up of 99 months (range 4-137) after initiation of first cytoreductive therapy within the protocol, median OS of all 169 patients was 10.5 years, with 10.5 years for those treated with and 6.1 years for those treated without autoSCT, yielding a hazard ratio of 0.26 (95% CI 0.13-0.54; p<.0001). Median PFS was 6.3 years, with 6.8 years for those treated with and 4.8 years for those treated without autoSCT (HR 0.39; 95% CI 0.23-0.67; p=0.0007). The 10-year incidence rate of t-MDS/ t-AML was 9% (1-18%). Diagnostic samples for assessment of the IGHV mutational status were available for 143 of 169 patients (85%). An unfavorable (unmutated of V3-21-containing) IGHV rearrangement was present in 104 patients (73%). Compared to the 39 patients with favorable IGHV, those with unfavorable VH had significantly worse PFS and OS (median PFS 5.1 years vs not reached, hazard ratio (HR) 2.47 (1.56-3.92), p=0.0001; median OS 9.1 years vs not reached, HR 2.0 (1.14-3.68), p=0.017). FISH was possible in 160 patients (95%) with results as follows: del 17p- 4 patients (3%), del 11q- without del 17p 40 patients (25%), trisomy 12 without del 17p- and del 11q- 20 patients (13%), del 13q- as sole abnormality 48 patients (30%), other karyotypes 20 patients (13%), normal karyotype 28 patients (17%). All 4 patients with del 17p- showed progressive disease after Dexa-BEAM mobilization and did not proceed to autoSCT. Whereas PFS (p <0.0001) and OS (p <0.0001) thus was strongly reduced in the 4 patients with del 17p-, no significant differences between the other subsets became evident: median PFS 1.0 years (del 17p-), 5.9 years (del 11q), 4.8 years (+12), 7.5 years (del 13q-), 7.7 years (normal); median OS 1.5 years (del 17p-), 10.5 years (del 11q-), not reached (+12), not reached (del 13q-), 10.3 years (normal). Conclusions: Unmutated IGHV remains an adverse prognostic factor after dose-escalated first-line therapy with autoSCT. In contrast, this strategy may overcome the unfavorable impact of the FISH karyotype del 11q- seen with conventional therapy. Disclosures: Hopfinger: Roche: Honoraria. Schmitz:Roche: Honoraria, Research Funding. Stilgenbauer:BayerScheringAG: Honoraria, Research Funding.

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Clinical Impact of an Internet-Based Tool to Help Guide Therapeutic Changes While Monitoring Patients with Chronic Myeloid Leukemia Receiving First-Line Tyrosine Kinase Inhibitor Therapy

Blood ◽

10.1182/blood.v120.21.4279.4279 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4279-4279

Author(s):

Kevin L. Obholz ◽

Daniel J. DeAngelo ◽

Michael J. Mauro ◽

Neil Shah ◽

B. Douglas Smith ◽

...

Keyword(s):

Research Funding ◽

Kinase Inhibitor ◽

Decision Support Tool ◽

Treatment Decisions ◽

Therapeutic Change ◽

Management Approach ◽

First Line ◽

Specific Patient ◽

Support Tool ◽

Expert Recommendations

Abstract Abstract 4279 Background European LeukemiaNet (ELN) and National Comprehensive Cancer Network (NCCN) recommendations are important resources to help guide the management of patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI) therapy. However, current guidelines are sometimes difficult to apply to all patient scenarios, particularly as they do not provide definite management recommendations for patients who have suboptimal responses to first-line TKI therapy. Furthermore, in a recent survey only 58% (N=132) of community oncologists made treatment decisions in line with expert recommendations for clinical scenarios in which patients had a suboptimal response to first-line therapy with imatinib. Online tools that provide expert clinical guidance have been proposed as one adjunctive approach to help clinicians make more informed treatment decisions. We previously reported that an online tool designed to provide expert guidance on adjuvant treatment of breast cancer may positively impact treatment decisions and thus potentially improve patient care (J Clin Oncol 29: 2011 [suppl; abstr 6063]). Aims/Objectives The goal was to determine whether an interactive online decision support tool providing expert guidance would help community practitioners make more informed therapeutic decisions for patients with CML who were receiving first-line TKI therapy. We sought to evaluate to what extent the expert recommendations changed the community practitioners' clinical approach. Methods An interactive decision support tool, developed with input from 5 CML experts who made treatment recommendations for 42 different patient scenarios, has been posted online at http://www.clinicaloptions.com/TreatingCML. Users of the tool enter specific factors such as patient age and duration of first-line TKI therapy, along with information on hematologic, cytogenetic, and/or molecular responses to first-line TKI therapy at 3, 6, 12 and 18 months. Before expert recommendations for that specific patient scenario are revealed, users are asked to enter their intended management approach. Once that is entered, the tool outputs a table showing the recommendations of the 5 CML experts based on the specific factors entered. Finally, the user is prompted to indicate whether the experts' recommendation confirmed or changed their intended management approach. User response data and intended treatment approaches will be tabulated and compared with the experts' recommendations. Results This resource was posted online July 2012 and had 161 unique users with 219 uses of the tool in the first 40 days. Among the users to date, 15% indicated that the experts' recommendations changed their intended management approach. A separate analysis of the in-tool recommendations showed that the experts considered not only guidelines, but also emerging data and their own clinical experience in making recommendations for specific patient scenarios. For example, ahead of similar recommendations included in the most recent update to the NCCN treatment guidelines for CML, the experts added a consideration in the tool suggesting a BCR-ABL/ABL ratio of 10% by QPCR as the threshold for guiding a therapeutic change at 3 months. Moreover, most of the experts (4 of 5) recommended a therapeutic change for patients in CCyR without MMR at 12 months if there was a concomitant increase in BCR-ABL ratio of 1 log or more and (3 of 5) also recommended a therapeutic change for patients without a MMR at 18 months regardless of whether their BCR-ABL/ABL ratio was increasing. Detailed comparisons of expert and user responses will be presented. Conclusions Preliminary data suggest that an online tool designed to provide customized, patient-specific expert advice may increase the number of clinicians who make optimal treatment decisions for patients with CML based on their response to first-line TKI therapy, and therefore, may be an important adjunct to the ELN and NCCN guidelines. Disclosures: Shah: ARIAD: Consultancy, Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Novartis: Consultancy. Smith:Bristol-Myers Squibb: Consultancy; Novartis: Consultancy. Radich:Ariad: Consultancy; Bristol-Myers Squibb: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Research Funding.

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Lenalidomide Treatment For Lower Risk Non-Deletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Prior To Azanucleosides

Blood ◽

10.1182/blood.v122.21.1507.1507 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1507-1507

Author(s):

Rami S Komrokji ◽

Maria G. Corrales-Yepez ◽

Najla H Al Ali ◽

Eric Padron ◽

Jeffrey E Lancet ◽

...

Keyword(s):

Overall Survival ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Research Funding ◽

Response Rates ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Abstract Introduction Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure. Methods This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21) Results We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS . The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69). Conclusion LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response. Disclosures: Komrokji: Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

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Lapatinib plus letrozole compared with letrozole alone as first-line therapy in hormone receptor positive HER2+ metastatic breast cancer (MBC): A quality-of-life (QOL) analysis

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1039 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1039-1039 ◽

Cited By ~ 2

Author(s):

B. N. Sherif ◽

B. Sherrill ◽

M. Amonkar ◽

Y. Wu ◽

J. Maltzman ◽

...

Keyword(s):

Hormone Receptor ◽

Patient Population ◽

Metastatic Breast ◽

Analysis Of Covariance ◽

Phase Iii ◽

First Line ◽

First Line Therapy ◽

Hormone Receptor Positive ◽

Line Therapy ◽

The Impact

1039 Background: A phase III randomized double-blind multicenter trial compared lapatinib plus letrozole (L+Let) with letrozole plus placebo (Let), as first-line therapy for hormone receptor positive (HR+) MBC. Median PFS, the primary endpoint of the study, in patients who were HER2+ was significantly prolonged for L+Let compared with Let (8.2 vs 3 months, Hazard Ratio (95% CI)=0.71(0.53,0.96), p=0.019). This analysis focuses on the impact of treatments on QOL in the HER2+ subgroup. Methods: QOL outcomes included the Functional Assessment of Cancer Therapy-Breast (FACT-B) total, FACT-general (FACT-G), and trial outcome index (TOI) scores assessed at screening, every 12 weeks and at withdrawal. Higher scores indicate better QOL. Changes from baseline were analyzed using analysis of covariance. In a responder analysis, patients achieving minimally important differences in QOL scores (QOL responders) were compared with Fisher's exact test. Results: Among 1,286 patients, 219 were identified as HER2+ (L+Let n=111; Let n=108). Baseline QOL scores were comparable in the two arms. In this population, mean changes in subscale and total QOL scores were generally stable over time in both treatment arms for patients who stayed on study. For example, on the FACT-B, the average change from baseline in both groups was positive at all scheduled visits through Week 48 and the maximum difference between arms was 2.6 points (CI: -5.8, 11). There were no significant differences between the two treatment arms in percentage of QOL responders (Table). Conclusions: The addition of lapatinib to letrozole significantly increases PFS while maintaining QOL when compared with letrozole alone thus confirming the clinical benefit of the combination therapy in the HR+, HER2+ MBC patient population. This combination provides an effective option in this patient population by maintaining QOL and delaying the need for chemotherapy and its accompanying side effects. [Table: see text] [Table: see text]

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Determinants of first-line treatment selection in advanced pancreatic ductal adenocarcinoma (PDAC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.468 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 468-468

Author(s):

Hui-Li Wong ◽

Ying Wang ◽

Yaling Yin ◽

Hagen F. Kennecke ◽

Winson Y. Cheung ◽

...

Keyword(s):

Overall Survival ◽

Locally Advanced ◽

Treatment Selection ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

The Impact ◽

First Line Treatment

468 Background: Chemotherapy options currently available for the first-line treatment of advanced PDAC include FOLFIRINOX (FX), gemcitabine with nab-paclitaxel (GP) and single agent gemcitabine (Gem). GP was introduced most recently and funded for clinical use in British Columbia (BC) in September 2014. In this retrospective analysis, we explore the impact of GP availability on first-line treatment selection and overall survival (OS) in advanced PDAC. Methods: The BC Cancer Agency provincial pharmacy database was used to identify patients (pts) who started FX, GP or Gem between January and August 2014 (pre-GP) or January and August 2015 (post-GP). Pts were eligible for inclusion if they received at least one cycle of first-line therapy for locally advanced or metastatic PDAC. Clinical data were extracted from electronic medical records. OS was defined as time from diagnosis of advanced PDAC to death and compared by treatment era, adjusting for age, ECOG, comorbidities, disease extent and baseline CA19-9. Results: 286 pts fulfilled eligibility criteria: 88 (31%) with locally advanced and 198 (69%) with metastatic disease. 131 and 155 pts were treated in the pre- and post-GP eras respectively. Prior to GP approval, 44% and 49% of pts received Gem and FX; this decreased to 21% and 33% after GP funding, with 46% of pts receiving GP in the latter period. Nine (7%) pts received GP in the pre-GP era, either through self-pay or addition of nab-paclitaxel after approval. There were no significant differences in pt characteristics across both eras. 46% of pts who received GP post approval had ECOG ≥ 2. The proportion of pts receiving second-line therapy was lower in the post-GP era (22% vs. 38%). Median OS in the post-GP era was 8.1 vs. 10.1 months in the pre-GP era; adjusted HR 1.28 (95% CI 0.96–1.71). Pts with ECOG ≥ 2 who received GP had a median OS of 6.5 months. Conclusions: After GP was funded, it became the preferred first-line regimen for advanced PDAC. Its more frequent use instead of FX did not appear to compromise overall survival even though a substantial proportion of pts were ECOG ≥ 2 and few pts received second-line therapy.

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

Blood ◽

10.1182/blood-2020-141525 ◽

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 < 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 < 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 < 20% compared to patients with CPCs ≥ 20% (p = 0.98). There was trend towards a better survival for patients with CPCs < 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.

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

Blood ◽

10.1182/blood-2019-127237 ◽

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.

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

Blood ◽

10.1182/blood-2018-99-113958 ◽

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.

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