scholarly journals Real-World Evidence on Shift in Treatment Practice and Adoption of Novel Agents for Patients with Chronic Lymphocytic Leukemia in the United States

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5013-5013
Author(s):  
Asher Chanan-Khan ◽  
Keri Yang ◽  
Sizhu Liu ◽  
Todd Zimmerman ◽  
Boxiong Tang ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Novel Agents ◽  
First Line ◽  
Real World Data ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
Oral Agents ◽  
The Impact

Abstract Introduction: Clinical availability of highly effective novel agents (including Bruton tyrosine kinase [BTK] and B-cell lymphoma 2 [BCL-2] inhibitors) is rapidly altering the therapeutic landscape of chronic lymphocytic leukemia (CLL) necessitating a review of treatment guidelines. However, there is limited real-world data to validate if the availability of these novel agents has translated to a true shift in treatment paradigm for patients treated in the community. As the majority of CLL patients are treated in non-academic community-based settings, we investigated the clinical adoption trends of commercially available FDA approved novel agents for treatment of CLL patients. In addition, given that the COVID-19 pandemic led to major alteration in clinical oncology practices, we further studied if this contributed to an alteration in the selection of therapeutic agents resulting in changes of CLL treatment patterns and the utilization of novel agents in the real-world setting. Thus, the objectives of this study were to examine the utilization pattern of various CLL therapies, as well as evaluate the pattern of adoption of novel agents for treatment and the impact of COVID. Methods: A retrospective observational study was conducted using the Flatiron Health database that comprised EHR-derived de-identified data. Adult patients (≥18 years) with newly diagnosed CLL from January 2014 to May 2021, with no prior treatment and who were continuously enrolled for at least 6 months before and 3 months after the index date, defined as the first date of CLL/SLL diagnosis were included. Treatment regimens were classified into seven mutually exclusive categories: bendamustine-based chemotherapy, other chemotherapy, anti-CD20-based therapy, ibrutinib, idelalisib, acalabrutinib and venetoclax. Further treatment categorization included chemotherapy vs. targeted therapy, and traditional IV vs. novel oral agents. The impact of the pandemic was examined by comparing the pre- and post-COVID cohorts (defined as 15 months pre- and post- of March 1, 2021). Descriptive analyses were conducted to examine the frequency of use of treatment regimens by quarter in each year, line of therapy and between different age, gender, US geographical region, insurance status, and race/ethnicity subgroups. Multivariable regression was conducted to examine factors associated with the likelihood of adoption of novel and oral agents. Statistical significance was determined at a p-value of less than 0.05. Results: A total of 3,037 newly diagnosed CLL patients (median age =73) were included in the study. Over half were male (62.3%), white (74.6%) and commercially-insured (54.1%). Patients were primarily treated in community practices (92%). Overall, a significant trend in adoption of novel agents was observed throughout the years following their approval (Figure 1A). Across the evaluation period, a significant decrease in chemotherapy use was observed from 61.3% (quarter 1, 2014) to 20% (quarter 2, 2021) in favor of targeted therapy as first-line therapy (Figure 1B). In contrast, the utilization of novel oral agents (vs. traditional IV agents) for first-line therapy increased from 9.5% to 70.9% for the same period (Figure 1C). Similar trends were observed for second-line and third-line therapies. Encouragingly, this change in treatment patterns was adopted comparably in all sociodemographic subgroups with no evidence of disparity. While there was no statistically significant difference between the pre- and post-COVID treatment landscape, the adoption of target and novel oral agents has been more pronounced with the COVID pandemic. Conclusions: Results from real-world data suggest that there is a clear shift towards the adoption of novel therapies with preference given to targeted agents and oral therapies in the US since 2014. Further research examining real-world outcomes associated with treatment regimens are needed to inform decision makers. Figure 1 Figure 1. Disclosures Chanan-Khan: Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; Ascentage: Research Funding; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BeiGene, Jansen, Ascentage: Honoraria; BieGene, Jansen, Ascentage: Consultancy. Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Zimmerman: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Ailawadhi: Karyopharm: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Takeda: Consultancy; GSK: Consultancy, Research Funding; Xencor: Research Funding; Cellectar: Research Funding; Medimmune: Research Funding; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; BeiGene, Ltd.: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy.

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.

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 ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 879-879 ◽  
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.

Serum Factors Predict Therapeutic Outcome In Patients with Chronic Lymphocytic Leukemia Treated In the CLL8 Trial of the German CLL Study Group (GCLLSG)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 918-918 ◽  
Author(s):  
Anna Fink ◽  
Natali Pflug ◽  
Raymonde Busch ◽  
Gunter R. Fingerle-Rowson ◽  
Barbara Eichhorst ◽  
...  
Keyword(s):  
Research Funding ◽  
Serum Levels ◽  
Serum Markers ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Advisory Committees ◽  
Serum Factors ◽  
First Line Therapy ◽  
Group A ◽  
Group D

Abstract Abstract 918 Introduction: Various factors are used to predict the clinical course of chronic lymphocytic leukemia (CLL). Here we evaluated the importance of the serum markers soluble CD23 (sCD23), β2-microglobulin (s-β2m) and thymidine kinase (s-TK) compared to other prognostic markers in patients (pts) receiving a first-line therapy with fludarabine and cyclophosphamide (FC) or FC plus rituximab (FCR) in the CLL8 trial of the GCLLSG. Methods: The analysis of the serum factors was centrally performed prior to treatment. Kaplan-Meier method and the log-rank test were used to compare progression-free survival (PFS) and overall survival (OS). A Cox regression model was applied for the multivariate analysis and included the following parameters: age, sex, disease stage, time from first diagnosis, ECOG performance status, presence of B-symptoms, white blood cell count, sCD23, s-TK and s-β2m genomic aberrations, IGHV mutational status, and type of therapy (FC versus FCR). Cut-off values for s-β2m and for s-TK were 3.5 mg/l and 10 U/l, respectively. Results: Since exploratory analyses suggested a particular role for sCD23, the contribution of sCD23 was examined in more detail. Data for sCD23 was available for 616 pts. This cohort was representative of the full trial population (n=817) with respect to baseline characteristics. Results for response rates, PFS, OS and sCD23 were available for 574 pts. Based on their sCD23 levels, pts were categorized by quartiles: 139 pts were assigned to group A (≤2807.5 U/mL), 145 to group B (>2807.5 U/mL -≤5507 U/mL), 146 to group C (>5507 U/mL-≤10920.5 U/mL) and 144 to group D (>10920.5 U/mL). Significant differences were observed with respect to complete remissions (CR): Pts of group A achieved a double fold CR rate (48.2%) compared to pts of group D (23.6%; p<0.001). Correspondingly, group D had the highest rate of non-responses (11.8%). PFS and OS were longest for pts with low serum levels for sCD23: The median PFS in group A was 51.9 months (mo) compared to 29.8 mo in group D (p<0.001). The median OS for group D was 62.5 mo, but was not reached in the other groups. Next multivariate analyses (Table1) were performed and showed that s-TK, 17p-deletion (del(17p)) and the type of therapy were independent predictors of PFS and OS. del(17p) was the strongest adverse factor for both PFS and OS. sCD23 and IGHV were independent prognostic factors for PFS but not for OS. s-ß2m, age and ECOG status independently predicted OS. Finally, we investigated whether combinations of different serum markers would define distinct risk groups. Using the three serum markers, four risk categories were defined: Low risk (LR) = no serum factor elevation, intermediate risk (IR) = either s-ß2m or s-TK high, but sCD23 low, high risk (HR) = high s-ß2m and s-TK, but low sCD23, and very high risk (VHR) = high sCD23, regardless of s-ß2m and s-TK. Median PFS was significantly different for the four groups, with 59.7, 49.3, 35 and 29.8 months for LR, IR, HR, and VHR patients respectively (p<0.001). However, the difference between HR and VHR was not statistically significant (p=0.2). Conclusion: Elevated serum levels of s-ß2m, s-TK, and sCD23 predict poor outcome after first-line therapy with FC or FCR in pts with CLL, independently of other features such as IGHV status or del(17p). Measurement of sCD23 in addition to s-TK and s-ß2m seems to allow a more precise prediction of PFS. Disclosures: Fink: Roche: . Pflug:Roche: Travel grants. Eichhorst:Roche: Research Funding, Travel grants. Wendtner:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants. Mendila:Roche: Employment. Wenger:Roche: Employment. Stilgenbauer:Amgen: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Sanofi Aventis: Research Funding. Hallek:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fischer:Roche: Research Funding, Travel grants.

A Randomised Dose De-Escalation Safety Study of Oral Fludarabine, ±Oral Cyclophosphamide and Intravenous Rituximab (OFOCIR) As First-Line Therapy of Fit Patients with Chronic Lymphocytic Leukaemia (CLL) Aged ≥65 Years – End of Recruitment Analysis of Response and Toxicity of the Australasian Leukaemia and Lymphoma Group (ALLG) and CLL Australian Research Consortium (CLLARC) CLL5 Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 436-436 ◽  
Author(s):  
Stephen P Mulligan ◽  
Devinder S Gill ◽  
Paul Turner ◽  
William E. P. Renwick ◽  
Rosemary Harrup ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Research Funding ◽  
Rating Scale ◽  
Therapy Response ◽  
Patient Choice ◽  
First Line ◽  
Patient Cohort ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
Grade 3

Abstract Abstract 436 Background: Combination immunochemotherapy with fludarabine (F), cyclophosphamide (C) and rituximab (R) gave superior progression free and overall survival compared to FC in the CLL8 Study. The median age in CLL8 was 61 years compared to a median age for overall CLL patients of 72 years. There is ongoing debate regarding the tolerability and safety of FCR in elderly patients, and what are the most appropriate criteria for selection of therapy. Methods: Previously untreated patients with progressive CLL aged ≥65 were randomised to one of three treatment regimens FR5, FCR3 and FCR5 as follows: (i) F 24mg/m2 po D1-5 + R (375 mg/m2 C1, 500mg/m2 C2-6) iv D1 (FR5), (ii) F 24mg/m2 po and C 150mg/m2 po D1-3 + R iv D1 (FCR3) or (iii) F 24mg/m2 po + C 150mg/m2po D1-5 + R iv D1 (FCR5), all given at 4 weekly intervals for an intended 6 cycles. The dosage of FCR5 is equivalent to standard 3 day IV FCR in the CLL8 Study. Patients were administered their therapy arm with no dose reduction but fludarabine dose was reduced if the eGFR was 50–69ml/min. Therapy was delayed up to 2 weeks if there was grade 3 or 4 toxicity, and if unresolved after 2 weeks, patients were taken off study. If toxicity resolved to grade 2 or less, therapy proceeded. Results: Recruitment of all 120 randomised patients was completed in July 2012. An analysis was performed with a cut-off date of 5 May, 2012 at which time there were 117 of 120 recruited from 29 centres in Australia and New Zealand. Median age was 71.7 (range 65–83) years. Binet stage at registration was progressive A – 20 (17.1%), B – 55 (47.0%) and C – 42 (35.9%). Response data are shown in table 1 for the total patient cohort - no analysis has been performed to date by treatment arm. Analysis of grade 3 and 4 toxicity events by Cumulative Illness Rating Scale (CIRS) score and age are shown in Tables 2 and 3 with data available at the cut-off date. Conclusions: Oral F(C)R therapy appears generally safe and well tolerated in CLL patients aged ≥65 years requiring first-line treatment according to data available at end of recruitment. Using stringent stopping criteria with delay of 2 weeks for recovery of grade 3 or 4 toxicity but no dose reduction, ∼40% of patients stop early due to toxicity, intercurrent illness or patient choice. Based on the 66 patients with completed Final Pathological Staging 2 months after end of therapy, response rates appear high with an overall response rate (ORR) of 92.3%. For this relatively fit elderly patient cohort, neither a CIRS score of 0 to 6, nor age predicted for grade 3 and 4 toxicity. Disclosures: Mulligan: Roche: Consultancy, Research Funding, Speakers Bureau; Genzyme: Consultancy, Research Funding, Speakers Bureau.

scholarly journals Real-World Outcomes for Standard-of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4075-4075
Author(s):  
Michel Delforge ◽  
Marie-Christiane Vekemans ◽  
Sébastien Anguille ◽  
Julien Depaus ◽  
Nathalie Meuleman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Retrospective Chart Review ◽  
Standard Of Care ◽  
Real World Data ◽  
Advisory Committees ◽  
Treatment Regimens

Abstract Background: With the advent of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and, more recently, anti-CD38 monoclonal antibodies (mAbs), prognosis of patients with multiple myeloma (MM) has improved considerably. Unfortunately, even with these 3 major MM drug classes, most patients ultimately relapse and require further therapy. There remains an incomplete understanding of how patients who have received extensive therapy and with relapsed/refractory multiple myeloma (RRMM) are treated in routine clinical practice, as no standard-of-care exists for these patients, and what the outcomes are in this real-world setting. Objective: This study aims to evaluate the outcomes of patients with triple-class (IMiD, PI and anti-CD38 mAb) and triple-line exposed RRMM using real-world data from patients in Belgium. Methods: A multicenter, observational study, involving 7 non-academic and academic Belgian centers, was conducted based on a retrospective chart review of adult RRMM patients who started subsequent treatment from March 2017 through May 2021 after having received ≥3 lines of therapy including at least an IMiD, a PI, and anti-CD38-directed therapy (tri-exposed). Data were captured in an electronic case report form (Castor EDC). Patients with an ECOG performance status of ≥2, who received prior CAR-T treatment or prior BCMA-targeted therapy, or with a known active or prior history of CNS involvement (or with clinical signs thereof), were excluded. All treatment lines initiated after becoming eligible were used in the analysis. Specifically, all treatment lines for patients meeting the eligibility criteria more than once in their entire follow-up were included as separate observations, with date of treatment initiation as specific baseline for each treatment line. Cox proportional hazards models were fitted to explore the prognostic value with Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Therapy (TTNT). Results: A total of 112 patients with 237 eligible treatment lines were included in the analysis; median follow-up was 16.6 months. In 45% of the initiated treatment lines, patients were refractory to 4 or 5 therapies, 62% had received ≥5 prior lines, 22% had extramedullary disease and in 48% of observations the time to progression in prior line was shorter than 4 months. After patients became tri-exposed, more than 50 unique treatment regimens were initiated, with the following being the most common: carfilzomib + dexamethasone (14%), pomalidomide + dexamethasone + chemotherapy (8%), and ixazomib + lenalidomide + dexamethasone (6%). Additionally, 4% of included observations were exposed to anti-BCMA agents. Overall, the following treatment classes were the most frequently started: PI only (19%), PI + IMiD combinations (17%), and regimens including anti-CD38 antibodies (15%). Median OS was 9.79 months [95% CI: 7.79; 12.22], median PFS was 3.42 months [95% CI: 2.79; 4.27], median TTNT was 3.61 months [95% CI: 3.09; 4.57]. Higher refractory status (p&lt;0.001), being male (p=0.001), older age (p&lt;0.001), shorter duration of prior lines (p&lt;0.001), shorter time to progression in prior line (p=0.025), and higher LDH levels (p&lt;0.002) were prognostic for worse outcomes for both OS (Figure 1) and PFS. Conclusions: This retrospective chart review of patients with tri-exposed RRMM in Belgium shows that real-world outcomes in terms of OS, PFS and TTNT are poor for these patients, with a median OS of &lt;10 months. A wide variety of treatment regimens used in clinical practice confirm the absence of a clear standard-of-care in this patient population. The literature also confirms that these poor outcomes observed in Belgium, for this subset of MM patients, are similar in other countries. These real-world data highlight the high unmet medical need in this patient population and critical need for new and effective treatment options. MD and MCV contributed equally to this work. Figure 1 Figure 1. Disclosures Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Vekemans: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceutica: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Depaus: Takeda: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Meuleman: iTeos Therapeutics: Consultancy. Strens: Realidad bvba: Consultancy. Van Hoorenbeeck: Janssen: Current Employment. Moorkens: Janssen-Cilag: Current Employment. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Dalhuisen: Janssen: Current Employment. Vandervennet: Janssen: Current Employment.

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 Chemoimmunotherapy for Patients with Chronic Lymphocytic Leukemia: MD Anderson Experience Beyond FCR300

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2047-2047 ◽  
Author(s):  
Dai Chihara ◽  
Philip A Thompson ◽  
Hagop M. Kantarjian ◽  
Susan M. O'Brien ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Research Funding ◽  
Risk Model ◽  
Lymphocytic Leukemia ◽  
Cox Proportional Hazards Model ◽  
High Dose ◽  
First Line ◽  
Ighv Gene ◽  
The Impact

Abstract Background: Novel, targeted therapies, such as ibrutinib, have transformed outcomes for patients with relapsed CLL and for older and unfit patients in the first-line setting. However, chemoimmunotherapy (CIT) remains the standard-of-care in fit patients. We reported that a subgroup of patients with IGHV mutated CLL experience prolonged PFS and potential cure after first-line CIT withfludarabine, cyclophosphamide and rituximab (FCR). However, FISH data was not available for this cohort of patients. Accurate knowledge of which patients are likely to experience prolonged PFS after FCR is essential to better select patients who may benefit from CIT in the era of novel therapies. Patients and Methods: We analyzed 492 patients who were treated on six clinical trials of first-line CIT between 2004 and 2015. Treatments were FCR, (n=277) FCR with high dose rituximab (n=65), FCR plusmitoxantrone (n=30), FCR plusalemtuzumab (n=60) and FCR with GM-CSF (n=60). Progression-free survival (PFS) and overall survival (OS) were calculated and pretreatment characteristics were evaluated for association with survival outcomes using a Cox Proportional Hazards model. Cumulative incidence was calculated by competing risk (death without event) regression analysis. Results: The median age of patients was 59 (range 28-84). Sixty-seven percent of the patients were male, 33% of the patients had mutated IGHV gene. Thirty percent of patients had del(13q), 19% had Trisomy12, 21% had del(11q), 8% had del(17p) and 21% were negative by FISH. Fifty-nine percent of patients received six cycles of CIT. With a median follow up duration of 6.2 years, the median PFS and OS were 6.3 years and not reached, respectively. Recently reported risk model by Rossi and colleagues using IGHV mutation status and FISH results (Blood 2015) discriminated PFS very well; 5-year PFS for low risk {mutated without del(11q)}, intermediate risk {unmutated or del(11q)} and high risk group {del(17p)} were 81%, 45% and 22%, respectively. Of note, there was a plateau in PFS after 8 years in patients with mutated IGHV gene, with 10-year PFS of 63% (Figure A). There was a significantly improved OS after relapse by the time. Three-year OS in patients who started salvage chemotherapy in 2004 to 2012 and 2012 to 2016 were 59% and 83%, respectively, suggesting the impact of improved salvage treatment options, particularly B cell signaling pathway inhibitors (Figure B). Five-year cumulative incidence of Richter transformation (RT) and AML/MDS was 4.8% and 4.2%, respectively (Figure C, D). There was a difference in onset for these two complications; 52% of RT occurred within 2 years, while 62% of AML/MDS occurred in 2-4 years after CIT. Overall, 110 patients (22.4%) died during the follow-up; the three major causes of death were CLL progression (4.9%), Richter transformation (3.7%) and AML/MDS (3.3%). Conclusion: Patients with mutated IGHV gene and who do not have del(11q) or del(17p) have favorable outcomes and demonstrate a plateau on the PFS curve, consistent with prior studies. Effective salvage therapy has improved outcomes at relapse, but the development of RT and AML/MDS remain major causes of mortality in CLL patients. Given favorable outcomes for patients with mutated IGHV gene treated with FCR, further studies are warranted to identify predictors of non-response among the mutated patients, risk factors for development of AML/MDS and RT and whether choice of first-line therapy can modulate this risk. Disclosures Thompson: Pharmacyclics: Consultancy, Honoraria. O'Brien:Janssen: Consultancy, Honoraria; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding. Jain:Servier: Consultancy, Honoraria; Novimmune: Consultancy, Honoraria; Incyte: Research Funding; Celgene: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Novartis: Consultancy, Honoraria; Abbvie: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Infinity: Research Funding. Wierda:Abbvie: Research Funding; Novartis: Research Funding; Acerta: Research Funding; Gilead: Research Funding; Genentech: Research Funding.

scholarly journals Comparison of Outcomes in Chronic Lymphocytic Leukemia (CLL) with the Addition of Rituximab to Initial Treatment: A Comparative Effectiveness Analysis in the Province of British Columbia (BC), Canada

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3344-3344 ◽  
Author(s):  
Lauren J. Lee ◽  
Alina S. Gerrie ◽  
Helene Bruyere ◽  
Tanya L. Gillan ◽  
Stephen J.T. Huang ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Hematologic Malignancy ◽  
Large Population ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
Continuous Variables ◽  
First Line ◽  
Free Survival

Abstract Background: Clinical trials report that chemoimmunotherapy with rituximab (R) improves overall survival (OS) and progression-free survival in the treatment (tx) of symptomatic CLL patients (pts). R has been available for first-line CLL tx in BC, population 4.5 million, since 2004. We compared clinical outcomes with and without addition of R to chemotherapy in a large unselected provincial cohort of pts treated for CLL, to determine the "real world" effectiveness of addition of R to standard chemotherapy. Methods: Three large provincial databases (db) were used to identify eligible pts: the BC Provincial CLL db, the BC Lymphoid Cancer db, and the Providence Hematology CLL db. All pts who received minimum 1 cycle of first-line tx for confirmed CLL were included. Pts with > 1 hematologic malignancy (n=8) were excluded. Baseline features of pts treated with (+R) or without R (No R) were compared using Chi-squared for categorical and Kruskal-Wallis test for continuous variables. OS was calculated from date of initial tx to date of death from any cause. Treatment-free survival (TFS) was calculated from date of initial tx to date of next tx/death from any cause. Multivariate analysis (MVA) was performed using Cox proportional hazard models to evaluate the effect of R on OS/TFS, after controlling for covariates including age (³60 yrs vs <60 yrs), Rai stage (3-4 vs 0-2), CD38 status (pos vs neg), presence of 17p (17p-) and 11q (11q-) deletions, and first-line tx with purine analogs (PAs). Results: A total of 1784 pts diagnosed with CLL from 1973-2014 were identified, of which 726 pts (41%) received tx in follow-up. Of treated pts, 393 (54%) received R and 333 (46%) received chemotherapy alone. Among the No R group, tx included: chlorambucil 56%; fludarabine (F) 34%; cyclophosphamide (C)-based 8%; cladrabine 2%. Among the +R group, tx included: FR 75%; C-based + R 17%; FCR 7%; chlorambucil + R 1%. 103 pts underwent bone marrow transplant (BMT) during their tx course (19% No R vs 10% +R, P=.002). Median age at diagnosis (dx) and tx between groups were not statistically different (No R vs +R: 60.6 vs 60.8 yrs and 64.7 vs 63.9 yrs, respectively). There were no clinically significant differences in diagnostic parameters including % with elevated LDH, lymphocyte count >20x109/L , Rai stage 3-4. Median follow-up time in survivors was longer in the No R group (13.0 vs 6.8 yrs, P<.001). Among 467 pts with known CD38 status, CD38 pos was more common in +R vs No R groups (47 vs 36%, P=.02). FISH was performed in 586 pts, with no significant differences in abnormalities between tx groups. Poor-risk FISH, 17p- or 11q-, were present in 29% (No R) and 27% (+R). Median time from dx to initial tx was 2.8 yrs (range 0-20.6) in No R vs 2.5 yrs (range 0-22.7) in +R groups (P=.84). OS was longer in the +R cohort (median OS 11.8 vs 7.1 yrs, P<.001), Fig. 1. Significant improvements in OS were also seen in pts <60 yrs of age at tx (median OS 11.3 vs 3.1 yrs, P<.0001), without 17p- (median OS 9.3 vs 5.2 yrs, P<.0001), and treated with PAs (median OS 9.4 vs 6.4 yrs, P=.0001). Median TFS was longer in pts treated with R (3.3 vs 2.3 yrs, P= .004), Fig. 2, and in those without 17p- (median TFS 3.1 vs 1.3 yrs, P<.001). MVA confirmed that the addition of R to chemotherapy remained a strong independent predictor of mortality (HR 0.66, 95% CI: 0.44-0.98, P=.04) and TFS (HR 0.6, 95% CI: 0.46-0.79, P<.001) after controlling for covariates. Other independent predictors of OS included age ³60 yrs (HR 2.77, 95% CI 1.87-4.10, P<.001) and presence of 17p- (HR 1.23, 95% CI 1.62-3.76, P<.001), whereas for TFS, presence of 17p- (HR 2.08, 95% CI: 1.49-2.91, P<.001) and CD38+ (HR 1.32, 95% CI: 1.03-1.68, P=.025) were independent negative predictors. Conclusion: In this large, population based cohort of pts treated for CLL, we confirm that the addition of R to chemoimmunotherapy as initial tx significantly improves OS, resulting in a 44% lower risk of overall mortality (95% CI, 2% to 66%) after controlling for covariates. We have also demonstrated that the addition of R to first-line therapy significantly delays the time to subsequent therapy, a finding not previously reported in a population based setting to our knowledge. This study complements clinical trial [Hallek, Lancet 2010] and US Registry data [Danese, Blood 2011], demonstrating benefit of the addition of R to standard therapy for first-line treatment of CLL and shows the generalizability of such results in a real world setting. Figure 1 Figure 1. Disclosures Gerrie: Roche: Honoraria, Research Funding. Ramadan:Roche: Honoraria, Research Funding.

scholarly journals Natural History of Skeletal Related Events in Patients with Multiple Myeloma Who Received First- and Second- Line Therapy with Novel Agents: Results from a Single Center Analysis in 620 Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4326-4326
Author(s):  
Evangelos Terpos ◽  
Nikolaos Kanellias ◽  
Eftathios Kastritis ◽  
Maria Gavriatopoulou ◽  
Vassilis Koutoulidis ◽  
...  
Keyword(s):  
Research Funding ◽  
Novel Agents ◽  
Long Bone ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Skeletal Related Events ◽  
First Relapse

Introduction: Skeletal-related events (SREs) that include pathological fractures, spinal cord compression (SCC) and need for radiotherapy or surgery to the bone are frequent complications of multiple myeloma (MM). Although the incidence of SREs at diagnosis is well-documented, there is limited information for the natural history of SREs during treatment with novel agents. Thus, we evaluated the SRE rate in MM patients who received frontline and second line therapy with proteasome inhibitors (PIs) or immunomodulatory drug (IMiD)-based therapies and explored possible correlations with disease or genetic features and type of treatment. Methods: MM patients who received frontline therapy in our center (Department of Clinical Therapeutics, University of Athens, Greece), between 2007-2017, were included in this analysis. Patients had a whole-body skeletal survey using either conventional radiography (WBXR) or low-dose CT (WBLDCT) at diagnosis and then at the time of relapse or whenever clinically indicated. Magnetic Resonance Imaging (MRI) of the spine and pelvis at diagnosis was recorded when available. SNPs in genes that are involved in bone destruction in osteoporosis were also evaluated: LRP5 (rs4988321), GC vitamin D (rs4588), TNFRSF11A (rs3018362), DKK1 (rs1569198), RANKL (rs9594759), OPG (rs6469804) and ERS1 (rs1038304). Results: In total, 620 consecutive patients with symptomatic MM (316M/304F, median age: 65 years) were studied. The median follow-up was 54 months. At diagnosis, osteolytic disease was present in 408 (66%) patients. MRI was available in 390 patients: 149 (38%) patients had focal, 139 (36%) diffuse, 81 (21%) normal and 21 (5%) variegated pattern of marrow involvement. SREs were observed in 271 (44%) patients at diagnosis: 213 (34%) presented with pathological fractures (183 with vertebral fractures, 18 with rib fractures and 15 with long bone fractures; 32 patients had both vertebral and long bone or rib fractures), while 34 (5.5%) patients needed surgery to bone, 45 (7.2%) radiotherapy and 31 (5%) patients presented with SCC. The incidence of SREs was higher in patients with osteolytic lesions (76.4% vs. 12.4%, p<0.0001) or abnormal MRI pattern (49% vs. 11.3%, p<0.0001) at diagnosis. No correlation was found between the presence of SREs at diagnosis and a specific SNP of those studied. Frontline therapy with IMiD-based regimens was given in 38% of patients; 27% patients received bortezomib-based regimens and 28% both IMiD and bortezomib-based therapies (VTD or VRD); 7% received only conventional chemo. Bisphosphonates (BPs) were given to 465 patients (75%) at diagnosis; the vast majority (91%) received zoledronic acid. The remaining 155 patients did not receive upfront BPs, mainly due to renal insufficiency. During first line treatment, 39 (6.3%) patients developed a SRE: 25/341 (7.3%) on bortezomib- (including combos with an IMiD) and 14/235 (6%) on IMiD-based regimens. At the time of first relapse, 4.5% of patients presented with new fractures and 12% required local radiotherapy to bone (SRE rate: 16.5%). The rate of SREs at first progression was much higher in patients who did not receive upfront BPs (92.3% vs. 7.7%). There was no difference in the incidence of SREs at first relapse between patients who received PI- vs. non-PI-based regimens as first line therapy (54.2% vs. 45.8%, p=0.544). During second line therapy, 12.2% of patients developed a SRE, with no difference regarding the second line therapy (PI- or IMiD-based regimens). In total, 126 (20.3%) patients developed at least one SRE, during the course of the first and second line of therapy; this was more common in those who presented with an SRE at diagnosis (33% vs 12%; p<0.03). Conclusions: Our data, which constitutes one of the few systematic reports on the incidence and characteristics of SREs in the era of novel agents, indicate that SREs remain a significant complication in MM. Despite high response rates after first line therapy and the broad use of BPs, more than 20% of patients develop a new SRE during the first and second line treatment or at the time of first relapse. Importantly, patients who do not receive BPs due to renal impairment develop very frequently SREs, suggesting an unmet need in this setting. More effective frontline therapies or more potent bone-targeted agents (denosumab or anti-sclerostin drugs) may manage to further reduce the SREs rate in MM patients, especially in those who cannot receive BPs. Disclosures Terpos: Celgene: Honoraria; Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria. Kastritis:Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. Gavriatopoulou:Amgen: Honoraria; Takeda: Honoraria, Other: Travel expenses; Janssen: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses. Dimopoulos:Sanofi Oncology: Research Funding.

scholarly journals Real-World Testing Patterns for Risk Assessment and Implications on the Adoption of Novel Therapeutics in Chronic Lymphocytic Leukemia: IGHV Mutation Status, FISH Cytogenetic, and Immunophenotyping

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4078-4078
Author(s):  
Asher Chanan-Khan ◽  
Keri Yang ◽  
Tom Liu ◽  
Todd Zimmerman ◽  
Boxiong Tang ◽  
...  
Keyword(s):  
Risk Factor ◽  
High Risk ◽  
Real World ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Novel Agents ◽  
Newly Diagnosed ◽  
Mutation Status ◽  
Factors Associated ◽  
To Receive

Abstract Introduction: Prognostic testing, including immunoglobulin heavy-chain variable region gene (IgHV) mutation status, cytogenetic abnormalities by fluorescence in situ hybridization (FISH), and immunophenotyping has been recommended in all newly diagnosed patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) prior to treatment initiation, and even in previously treated patients in some settings. Recent data have shown that disease with high-risk genetic features is better managed with novel agents than traditional chemoimmunotherapy. As such, the need for testing has become more relevant for disease management. However, there is limited recent data on real-world patterns of testing for risk factor assessment and in-turn, patterns of evidence-based treatment selection. This study aimed to examine: (1) the frequency and results of testing, (2) timing of testing by line of therapy, and (3) factors associated with the receipt of testing. Methods: De-identified data from the Flatiron Health EHR-derived database was used to identify patients who were ≥18 years old with newly-diagnosed CLL/SLL, who had ≥6-month continuous enrollment, and no prior treatment from January 2014 to May 2021. Testing evaluated included IgHV mutation status, FISH cytogenetic (11q deletion [del(11q)], 13q deletion [del(13q)], 17p deletion [del(17p)], Trisomy 12 [+12]) and other biomarkers (including CD38 and ZAP-70) by immunophenotyping. Descriptive analyses were conducted to examine the frequency and results in the overall population, and compared by patient characteristics and across sociodemographic groups. Multivariable logistic regression was conducted to examine factors associated with the likelihood of receiving testing. Statistical significance was determined as a p-value of &lt;0.05. Results: A total of 3,037 CLL patients were included (median age=73, 62.3% male, 74.6% white). The majority of patients (92%) received treatment in community practices, with 54.1% commercially-insured. We observed over half of CLL patients did not receive risk factor testing (Figure 1): IgHV mutation analyses (76.2%, n=2,315), FISH (61.5%, n=1,868) and immunophenotyping (72.1%, n=2,190). Of those who had testing, the majority (99%) had it done once prior to starting first-line therapy. Significant differences in the receipt of testing were observed between different age, gender, race/ethnicity, and regional subgroups (Table 1). Among patients who received testing, the presence of high-risk biomarkers was as follows: unmutated IgHV (56.1%), del(17p) present (14.4%), del(11q) present (16.9%), and CD38 present (30.8%). Compared to patients &lt;65 years, testing results in elderly patients ≥65 years showed a lower presence of unmutated IgHV (53.8%) and del(11q) (15.7%) while higher del(17p) (14.7%) and +12 (28.1%). No significant disparity was observed in white vs. non-white patients except for a lower incidence of mutated IgHV and del(13q) presence. Compared to tested men, tested women had a lower presence of unmutated IgHV (53.9%), del(11q) (11.4%) and CD38+ (25.8%) while higher del(17p) (18.2%). We then investigated the impact of risk testing on therapy selection, and noted that patients with del(17p) had a higher likelihood than those who tested negative (73.6% vs. 48.4%) of being treated with novel agents (ibrutinib, acalabrutinib, or venetoclax). In contrast, 26.4% of those who tested del(17p) present and 39.8% among those who did not get tested received chemotherapy. Multivariable regression showed that patients who were older (≥65 years), female or those living in the west of U.S. were significantly less likely to receive testing. Conclusions: The NCCN guidelines recommend novel agents for patients with high-risk CLL/SLL. Thus, all patients are advised to complete risk-factor testing for both prognostication and selection of optimal, evidence-based therapy. Our real-world data highlights not only a significant gap in testing, but that this suboptimal testing is more common in vulnerable populations. We observed that despite identification of del(17), a quarter of CLL patients failed to receive novel agents in the frontline setting. Our analysis identified an unmet need for further education and refinement of clinical practice. This is necessary to achieve the best clinical outcome in CLL patients through robust risk-assessment testing and optimal therapeutic triaging. Figure 1 Figure 1. Disclosures Chanan-Khan: BieGene, Jansen, Ascentage: Consultancy; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage: Research Funding; Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; BeiGene, Jansen, Ascentage: Honoraria. Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Zimmerman: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Ailawadhi: Ascentage: Research Funding; Medimmune: Research Funding; Pharmacyclics: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Genentech: Consultancy; Xencor: Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; Cellectar: Research Funding; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; AbbVie: Consultancy; Beigene: Consultancy; Takeda: Consultancy.

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