Chemoimmunotherapy Research Articles

"Double-Hit" Chronic Lymphocytic Leukemia, Involving the TP53 and MYC Genes.

Although the 17p deletion [del(17p)] is rare in cases of treatment-naive chronic lymphocytic leukemia (CLL), its frequency is higher in refractory/relapsed CLL – particularly in patients undergoing chemo(immuno)therapy. TP53 disruption (deletion and/or mutation) is the strongest prognostic factor for refractoriness to chemotherapy; the use of Bruton tyrosine kinase inhibitors and BCL2 inhibitors is then indicated. Rare cases of CLL can also harbor translocation or gain of the MYC oncogene. “Double-hit CLL” (with del(17p) and MYC gain) is associated with a very poor prognosis. The prognostic impact of TP53 disruption with MYC aberrations in patients receiving targeted therapies must now be evaluated.

Management of Persistent SARS-CoV-2 Infection in Patients with Follicular Lymphoma

Introduction: There is no consensus on the management of the coronavirus disease (COVID-19) in patients with secondary immunosuppression due to either an underlying hematological disease or to the effects of immunochemotherapy (ICT). Some of them may present persistent infection with multiple relapses of COVID-19, requiring several admissions. This study evaluated the clinical characteristics and outcomes after treatment of 5 patients with follicular lymphoma (FL), previously treated with ICT, who developed several episodes of COVID-19. Methods: We analyzed the clinical evolution and response to treatment with antiviral agent, steroids, and convalescent plasma in 5 patients with FL and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistent infection. Reverse transcriptase polymerase chain reaction tests and peripheral blood immunophenotype were performed for all patients. Results: All patients required hospitalization due to pneumonia with severity criteria and were re-admitted after a median of 22 days (13–42) from the previous discharge. They all showed B-cell depletion by immunophenotyping, and no traces of immunoglobulin antibodies against SARS-CoV-2 were detected in any of the cases. The survival rate was 80%. Conclusion: The combination therapy evidenced clinical benefits, demonstrating its capacity to control infection in immunosuppressed FL patients treated with ICT.

High Resolution Assessment of Minimal Residual Disease (MRD) By Next-Generation Sequencing (NGS) and High-Sensitivity Flow Cytometry (hsFCM) in the Phase 3 GAIA (CLL13) Trial

High Resolution Assessment of Minimal Residual Disease (MRD) By Next-Generation Sequencing (NGS) and High-Sensitivity Flow Cytometry (hsFCM) in the Phase 3 GAIA (CLL13) Trial

Event-Free and Overall Survival in over 6,000 Patients Treated with Frontline Immunochemotherapy for Follicular Lymphoma between 2002-2018: First Report from the International FLIPI24 Consortium

Event-Free and Overall Survival in over 6,000 Patients Treated with Frontline Immunochemotherapy for Follicular Lymphoma between 2002-2018: First Report from the International FLIPI24 Consortium

Real-World Evidence on Therapeutic Strategies and Treatment-Sequencing in Patients with Chronic Lymphocytic Leukemia: An International Study of Eric, the European Research Initiative on CLL

Real-World Evidence on Therapeutic Strategies and Treatment-Sequencing in Patients with Chronic Lymphocytic Leukemia: An International Study of Eric, the European Research Initiative on CLL

Variance in Practice between Experts and Oncology Healthcare Professionals for Follicular Lymphoma: Analysis of an Online Treatment Decision Tool

Variance in Practice between Experts and Oncology Healthcare Professionals for Follicular Lymphoma: Analysis of an Online Treatment Decision Tool

Addressing a New Challenge in Chronic Lymphocytic Leukemia: Outcomes of Therapies after Exposure to Both a Covalent Bruton's Tyrosine Kinase Inhibitor and Venetoclax

Addressing a New Challenge in Chronic Lymphocytic Leukemia: Outcomes of Therapies after Exposure to Both a Covalent Bruton's Tyrosine Kinase Inhibitor and Venetoclax

Impact of Immunochemotherapy with R-Bendamustine or R-CHOP in the Post-Induction Management of Treatment Naïve Advanced Stage Follicular Lymphoma Patients: A Subset Analysis of the FOLL12 Trial By the Fondazione Italiana Linfomi (FIL)

Impact of Immunochemotherapy with R-Bendamustine or R-CHOP in the Post-Induction Management of Treatment Naïve Advanced Stage Follicular Lymphoma Patients: A Subset Analysis of the FOLL12 Trial By the Fondazione Italiana Linfomi (FIL)

Real-World Outcomes of Patients with Primary CNS Lymphoma (PCNSL): A Report from the Australasian Lymphoma Alliance (ALA)

Real-World Outcomes of Patients with Primary CNS Lymphoma (PCNSL): A Report from the Australasian Lymphoma Alliance (ALA)

Outcomes of Primary Bone Diffuse Large B-Cell Lymphoma in the Rituximab Era: A Multicenter Retrospective Analysis

Outcomes of Primary Bone Diffuse Large B-Cell Lymphoma in the Rituximab Era: A Multicenter Retrospective Analysis

Evaluating Front Line Treatment Regimens for Waldenstrom Macroglobulinaemia: A Systematic Review and Meta-Analysis

BackgroundWaldenstrom macroglobulinemia (WM) is a rare haematological malignancy characterised by infiltration of the bone marrow by clonal lymphoplasmocytic cells and serum monoclonal IgM gammopathy. Rituximab based chemo-immunotherapy has long been the backbone of WM treatment. Bendamustine rituximab (BR), cyclophosphamide, dexamethasone rituximab (CRD) and bortezomib dexamethasone rituximab (BDR) are currently considered frontline options. The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib in combination with rituximab (IR) has recently shown efficacy in treatment naïve WM and has been approved for use in this setting. With the expanding number of treatment options and absence of randomised trials (RCTs) comparing IR with chemo immunotherapy, there is uncertainty as to the optimal frontline treatment for WM.MethodsThe aim of this systematic review was to compare the efficacy and safety of rituximab-based chemoimmunotherapy combinations and IR, in treatment naïve WM. Using a pre-specified protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), MEDLINE, Embase, BIOSIS and Cochrane Library databases were searched for articles published from inception of each database to present. We included trials studying newly diagnosed WM patients treated with rituximab-based chemo-immunotherapy or BTKi based regimens. Primary outcome measures were progression free and overall survival (PFS and OS) while secondary outcomes included response rates and adverse events. A meta-analysis of proportions (expressed as a percentage), with their 95% CI were calculated.ResultsOf the 753 unique records identified, 8 single arm studies, one phase II non-randomised non inferiority study and 3 Phase III RCTs met the inclusion criteria. The sample size ranged from 23 to 261. PFS at 1- and 2-years were higher in BR(91%, 87%) and IR (93%, 82%), compared to BDR (87.5%, 66.8%) and CRD (82%, 64%) . Combined complete response (CR) and very good partial response (VGPR) rates were also superior with BR (35%) and IR ( 26%) compared to BDR (9%), Bortezomib- Rituximab (8% ) and CRD ( 7%) (Figure 1). The bortezomib bendamustine rituximab ( BBR) regimen was evaluated in only one study but showed an impressive CR/VGPR rate of 47% and a PFS at 3 years of 75%. Bleeding and atrial fibrillation were more common with IR, while neuropathy was more prevalent with bortezomib based regimens.ConclusionWe present the first systematic review and meta-analysis evaluating frontline treatment options for WM in the BTKi era. Our findings suggest that bendamustine-based regimens may be superior in terms of depth of response and PFS. Longer follow up of the IR treated patients on the INNOVATE trial is however required to perform a definitive comparison of the regimens. The differential efficacy of these treatments in genomic subtypes of WM (based on MYD88 and CXCR4 mutational status) is an important question to be answered in future trials. While chemo-immunotherapy remains a potent, fixed duration option for newly diagnosed WM, BTKi based regimens are a valid alternative for patients who prefer an oral treatment or who are unfit for cytotoxic therapy. With the expanding number of treatment options for WM, RCTs comparing BTKi/immunotherapy with chemo-immunotherapy regimens are called for. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Primary Analysis of ZUMA-7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard-of-Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma

Primary Analysis of ZUMA-7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard-of-Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Initial Safety Results from a Phase II Study of Acalabrutinib Plus RICE Followed By Autologous Hematopoietic Cell Transplantation and/or Acalabrutinib Maintenance Therapy for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background: Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) often have a poor prognosis despite therapies using second-line chemoimmunotherapy (CIT). Achievement of complete response (CR) with second-line therapy is associated with improved long-term outcomes. Unfortunately, only 25-35% of patients achieve CR with standard CIT regimens alone. The addition of novel targeted agents such as Bruton Tyrosine Kinase inhibitors (BTKi) to second-line therapy may offer improved treatment responses given the importance of B-cell receptor (BCR) signaling in DLBCL. BTK has been shown to be essential for BCR-mediated activation of the NF- κB/Rel family of transcription factors and BCR signaling has been recognized as a key pathway in the pathogenesis of DLBCL. Moreover, NF-κB activity relies upon chronic active BCR signaling in activated B-cell-like DLBCL, which can be potentially blocked by kinase inhibitors targeting BTK. In this study we examine the feasibility and efficacy of adding the BTKi, acalabrutinib (A), to standard second-line therapy to improve disease response in patients with R/R DLBCL. Here we present initial safety and tolerability data for the ongoing study.Study Design and Methods: This is an open-label, prospective phase II trial (NCT03736616). Cohort A is open to R/R DLBCL patients eligible for autologous hematopoietic transplantation (HCT). Cohort B is open to R/R DLBCL patients considered ineligible for autologous HCT. The primary endpoint for cohort A is to estimate the confirmed CR rate (RECIL 2017 criteria) prior to autologous HCT in patients undergoing second-line CIT. The primary endpoint for cohort B is defined as the estimate of one-year progression-free survival in patients undergoing second-line induction and maintenance acalabrutinib therapy.Cohort A receive 2 cycles of standard RICE salvage CIT in combination with acalabrutinib, 100mg BID days 1-21 of a 21-day cycle (RICE+A). After 2 cycles of therapy, patients undergo autologous stem cell mobilization and collection. Patients then receive a 3 rd cycle of RICE in combination with acalabrutinib. PET-CT (PET3) is to be performed on day 15 of cycle 3 to assess response. Patients with CR or partial response (PR) after PET3 proceed to autologous HCT with BEAM conditioning within 28-42 days of PET3. Post-HCT CR patients receive acalabrutinib 100mg BID as maintenance therapy for 12 additional months. Protocol amendment in May 2021 allows for PET assessment (C2D15) prior to autologous stem cell collection (after cycle 3).Cohort B receive 3 cycles of RICE+A in 21-day cycles followed by PET-CT (PET3) on day 15 of cycle 3. Patients without progressive disease at PET3 continue with acalabrutinib maintenance up to 12 additional cycles until disease progression or unacceptable toxicity. Patients demonstrating progressive disease are withdrawn from study treatment but followed for outcomes.Results: Here we report initial safety and tolerability data for the ongoing study with data cutoff July 28, 2021. Twenty-two patients have been screened and 20 patients have received at least 1 cycle of RICE+A. Patient characteristics are shown in Table 1. Fifteen patients (79%) have completed 3 cycles of RICE+A. One patient (5%) discontinued due to an adverse event (AE; recurrent appendicitis), 3 patients (16%) discontinued due to progressive disease, and 1 patient is receiving ongoing RICE+A as of data cutoff. Hematologic AE have been observed in 17 patients (89%) with 74% being Grade 3/4. Amongst these, neutropenia was the most common AE occurring in 47% with all being Grade 3/4, and thrombocytopenia occurring in 32% with all being Grade 3/4. All hematologic AE recovered to baseline or grade 1 in median 7 days. Amongst non-hematologic AE, diarrhea occurred in 21% and 0% were Grade 3/4, nausea 16% with 0% Grade 3/4, and headache in 16% with 0% Grade 3/4. Discontinuation of therapy due to AE occurred in 1 patient (recurrent appendicitis) and dose reduction occurred in 1 patient (Gr 4 neutropenia). Temporary (per protocol) dose holds of A occurred in 9 patients (45%), primarily for cytopenias during concurrent RICE+A. Median duration for dose holds of A was 5.5 days.Conclusion: RICE+A is feasible with manageable primarily hematologic AEs similar to those reported for RICE alone. Enrollment and follow up is ongoing for efficacy endpoints and further toxicity assessment. [Display omitted] DisclosuresBensinger: BMS, Janssen, Poseida, Regeneron, Trillium: Research Funding; Amgen, BMS, Janssen, Sanofi: Speakers Bureau. Glennie: Pharmacyclics/Janssen: Speakers Bureau. Pagel: Pharmacyclics/AbbVie: Consultancy; Incyte/MorphoSys: Consultancy; MEI Pharma: Consultancy; Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Kite, a Gilead Company: Consultancy; Epizyme: Consultancy. Patel: Bristol Myers Squibb: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; BeiGene: Consultancy; TG Therapeutics: Consultancy, Speakers Bureau; Abbvie: Consultancy; Pharmacyclics: Consultancy; Morphosys: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; MEI Pharma: Consultancy; ADC Therapeutics: Consultancy; Lilly: Consultancy. OffLabel Disclosure:Acalabrutinib is not FDA approved for treatment of DLBCL and is discussed in the context of an ongoing clinical trial only.

Long-Term Results of Alliance A041202 Show Continued Advantage of Ibrutinib-Based Regimens Compared with Bendamustine Plus Rituximab (BR) Chemoimmunotherapy

Long-Term Results of Alliance A041202 Show Continued Advantage of Ibrutinib-Based Regimens Compared with Bendamustine Plus Rituximab (BR) Chemoimmunotherapy

Real-World Treatment Patterns and Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First-Line (1L) Therapy in the United States (US)

Background: There have been many advances in CLL treatments over the past decade, with a number of novel agents targeting molecular pathways within CLL cells receiving approval from the US Food and Drug Administration. Here, we assessed the evolution of molecular testing patterns, treatment patterns, and clinical outcomes over time in patients receiving 1L CLL treatment in a real-world US database.Methods: This was a retrospective cohort study using the Flatiron Health database, a longitudinal database comprising de-identified, patient-level, structured and unstructured data, curated via technology-enabled abstraction. During the study period, the de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. Patients aged 18 years and older who were diagnosed with CLL and initiated 1L treatment between December 2015 and December 2020 were selected. Participants who took part in a clinical trial in any line of therapy, or who had any other primary cancer diagnosis, were excluded. Baseline characteristics, including testing patterns, at initiation of 1L treatment were assessed using descriptive statistics. Treatment patterns and outcomes, such as time to next treatment or death (TTNTD), were analyzed. Kaplan-Meier analysis was used to estimate TTNTD.Results: Among 3654 patients with treatment-naive CLL who were selected from the de-identified database, the mean age at 1L treatment initiation was 70 years (range, 29-85); 64.3% of patients were male; 72.1% were White, 8.2% Black, 3.9% Hispanic/Latino, 1.0% Asian, and 14.9% were of other ethnicity/race. Approximately one-third (34.7%) of patients had Rai stage 0-I disease, 6.9% had stage II, 6.3% stage III, 11.5% stage IV, and 40.6% had undocumented Rai stage.Testing patterns: The majority of identified patients (3202/3654; 87.6%) had undergone cytogenetic testing, fluorescence in situ hybridization, or IGHV mutation testing. Compared with 2015-2016, testing rates were higher in 2019-2020 for chromosome 17p deletion (del(17p); 36.1% vs 45.7%, respectively; p<0.001) and for IGHV mutation status (84.7% vs 89.2%, respectively; p=0.003). Overall, 11.0% of patients had del(17p). Of those tested for IGHV (1472/3654; 40.3%), 58.3% had unmutated IGHV.Treatment patterns: The 10 most commonly used 1L CLL treatments, which overall represented 91.8% of all 1L treatments, and their evolution over time, are reported in Table 1. Of the patients receiving these top 10 1L treatment regimens overall, 45.7% received regimens including novel targeted oral agents, 33.4% received chemo-immunotherapy (CIT), and 19.7% received anti-CD20 monotherapy. Evaluation of each 2-year period shows that treatment patterns for the top 10 1L treatment regimens shifted, with use of novel targeted oral agents increasing from 27.1% (2015-2016) to 63.8% (2019-2020) (p<0.001), while use of CIT and chemotherapy decreased over time (Table 2). Approximately 30.0% (1088/3654) of 1L-treated patients went on to receive second-line treatments.Outcomes: Median TTNTD was 34.4 months for all patients receiving 1L CLL treatment, and 36.5 months for patients who received the 10 most common 1L treatments across the 6-year study period (n=3360). Median TTNTD was 47.0 months for patients who received novel targeted oral agents and 41.5 months for patients who received CIT (unadjusted p=0.16). When evaluating outcomes in patients with high-risk cytogenetics, median TTNTD was 29.1 months for patients with del(17p) and 37.2 months for those with unmutated IGHV, but was longer in those patients who received treatment with novel targeted oral agents (median TTNTD of 43.9 and 46.7 months, respectively; Table 3).Conclusions: This analysis provides the current state of 1L CLL testing and treatment patterns and outcomes in the US from 2015 to 2020. As expected, the use of novel targeted oral agents increased over time, with a corresponding increase in TTNTD. Clinical outcomes were improved in patients receiving novel targeted oral agents, both overall and in high-risk subgroups. Following on from this, a comparative study of TTNTD for novel oral agents versus CIT, and analyses of outcomes of different sequencing of therapies, will be conducted. [Display omitted] DisclosuresMato: Nurix: Research Funding; Johnson and Johnson: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; MSKCC: Current Employment; Sunesis: Consultancy, Research Funding; AstraZeneca: Consultancy; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genmab: Research Funding; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ravelo: Genentech, Inc.: Current Employment; Roche Holdings: Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. To: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Schuldt: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Johnson & Johnson: Divested equity in a private or publicly-traded company in the past 24 months. Biondo: Genentech, Inc.: Current Employment; Roche: Current holder of individual stocks in a privately-held company.

Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Single-Agent Ibrutinib Versus Real-World (RW) Treatments for Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL): Adjusted Comparison of Resonate-2™ with the Cllear and Lyon-Sud Rw Databases

IntroductionIbrutinib, a once-daily oral Bruton's tyrosine kinase inhibitor, has shown progression-free survival (PFS) or overall-survival (OS) benefit over chemoimmunotherapy (CIT) in multiple phase 3 studies in previously untreated patients with CLL, and significantly longer time to next treatment compared with CIT in previously untreated high-risk patients in a RW setting. We conducted an adjusted comparison of ibrutinib versus RW treatment for previously untreated CLL using patient-level data from the phase 3 RESONATE-2™ (NCT01722487) trial and RW databases from 2 countries.MethodsPreviously untreated patients with CLL, fulfilling RESONATE-2™ eligibility criteria (age ≥ 65, no del17p) were selected from 2 RW data sources containing electronic medical records for patients with CLL: Centre Hospitalier Lyon-Sud, France; CLLEAR CLL registry from 7 academic centers in the Czech Republic. PFS and OS were compared between patients from the ibrutinib arm of RESONATE-2™ with a median follow-up of 60 months, and those receiving physicians' choice (PC) treatment other than ibrutinib from the RW database, adjusting for differences in baseline characteristics including age, gender, del11q, IGHV status, RAI/BINET disease stage, and Eastern Cooperative Oncology Group (ECOG) score. Hazard ratios (HRs) for ibrutinib versus RW PC treatment were estimated using a multivariable Cox proportional hazards model including available baseline characteristics as covariates, and using an inverse probability weighted (IPW) Cox model with average treatment effect for treatment (ATT) weights derived from propensity scores estimated from a logistic regression including the same covariates.ResultsThe analysis included 136 patients from the RESONATE-2™ study receiving ibrutinib and 920 previously untreated RW patients receiving PC treatment (Lyon-Sud n = 162, CLLEAR n = 758). Baseline characteristics were generally balanced between treatment groups. The most common PC regimens contained CIT and were fludarabine + cyclophosphamide + rituximab (FCR) (n = 227), bendamustine + rituximab (BR) (n = 201), and rituximab + chlorambucil (R + Chlor) (n = 116). Older age, male gender, del11q and advanced disease stage were independent risk factors for PFS and OS. When comparing ibrutinib versus the overall PC cohort, the adjusted HR (95% confidence interval [CI]) was 0.24 (0.16-0.34) for PFS and 0.33 (0.21-0.52) for OS (both p < 0.0001). IPW-based comparative estimates were highly consistent for both PFS (HR = 0.27 [0.18-0.39]) and OS (HR = 0.39 [0.24-0.62]). ATT-weighted survival curves estimating PFS and OS for the RESONATE-2™ population as if treated with PC, showed a median value of 32.1 months and 72.5 months, respectively, while median values for Ibrutinib were not reached. When comparing ibrutinib versus FCR, BR, and R + Chlor, the adjusted HRs (95% CI) were 0.26 (0.17-0.38), 0.27 (0.18-0.41), and 0.27 (0.17-0.42), respectively, for PFS and 0.34 (0.20-0.56), 0.28 (0.16-0.49), and 0.61 (0.32-1.13), respectively, for OS (Figure).ConclusionsAdjusted comparisons of the RESONATE-2™ trial and RW patient-level data demonstrates significantly improved PFS and OS for ibrutinib versus physician's choice treatment (predominantly CIT) in previously untreated patients with CLL. PFS and OS benefit for ibrutinib was consistent across a range of common regimens: FCR, BR, and R + Chlor. These results are consistent with data from phase 3 studies and support the use of ibrutinib for first-line CLL treatment.Funding Source:Sponsored by Janssen Pharmaceutica NV, and Pharmacyclics LLC, an AbbVie Company. The RW databases are independently owned. Writing assistance was provided by Emma Fulkes and Liqing Xiao of Parexel and funded by Janssen Pharmaceutica NV. [Display omitted] DisclosuresDoubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Smolej: AbbVie, AstraZeneca, Gilead, Janssen-Cilag, and Roche: Consultancy, Honoraria, Other: Travel Grants. Šimkovič: AbbVie, AstraZeneca, Janssen-Cilag, Gilead, Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants. Lysak: Novartis, Janssen-Cilag, AbbVie; AstraZeneca: Honoraria, Research Funding. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Ferrant: AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; AstraZeneca: Honoraria; Janssen: Other: Travel, Accommodations, Expenses. Diels: Janssen: Current Employment. Cabrieto: Janssen: Current Employment. Nielsen: Janssen: Current Employment. Salles: Allogene: Consultancy; Regeneron: Consultancy, Honoraria; Velosbio: Consultancy; Takeda: Consultancy; Rapt: Consultancy; Genentech/Roche: Consultancy; Epizyme: Consultancy, Honoraria; Debiopharm: Consultancy; Genmab: Consultancy; Incyte: Consultancy; Ipsen: Consultancy; Janssen: Consultancy; Kite/Gilead: Consultancy; Loxo: Consultancy; Miltneiy: Consultancy; Morphosys: Consultancy, Honoraria; Novartis: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria.

Awareness, Knowledge, and Preferences of United States (US) Patients with Chronic Lymphocytic Leukemia (CLL) and Their Caregivers Related to Finite Duration (FD) Therapy and Minimal (Measurable) Residual Disease (MRD)

Awareness, Knowledge, and Preferences of United States (US) Patients with Chronic Lymphocytic Leukemia (CLL) and Their Caregivers Related to Finite Duration (FD) Therapy and Minimal (Measurable) Residual Disease (MRD)

Clinical and Economic Burden of Tumor Lysis Syndrome Among Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Introduction: Tumor lysis syndrome (TLS) can be a life-threatening complication in patients with hematologic malignancies. In chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), treatment guidelines identify a high risk of TLS for regimens containing anti-CD20-based chemoimmunotherapy (CIT), lenalidomide, obinutuzumab, or venetoclax. Patients who develop TLS require intensive care, adding to the overall clinical and economic burden of CLL/SLL. This study aimed to evaluate the clinical and economic burden of treatment-emergent TLS among patients with CLL/SLL treated with regimens with high risk of TLS.Methods: The IBM MarketScan Research Databases (01/01/2006-04/30/2020) were used to identify adults with CLL/SLL who initiated a CIT-, lenalidomide-, obinutuzumab-, or venetoclax-based regimen on or after 01/01/2007 or upon treatment approval date if post-2007 (index date) and had ≥12 months and ≥30 days of continuous eligibility pre- and post-index date, respectively. Treatment-emergent TLS was defined as developing TLS in the first 90 days of active treatment (based on claims with a TLS diagnosis or laboratory test results). The post-index period was divided into 30-day intervals until the end of the index regimen (earliest of start of next regimen or end of eligibility). Intervals pre-TLS were non-TLS intervals and all intervals starting from the TLS diagnosis were TLS intervals. If TLS occurred after the first 90 days of active treatment (non-treatment-emergent TLS), all intervals were non-TLS intervals and the post-index period was censored at TLS diagnosis. Per-patient-per-month (PPPM) healthcare resource utilization (HRU) and payer paid costs during TLS and non-TLS intervals were compared using rate ratios (RRs) and mean monthly cost differences (MMCDs), respectively, obtained from generalized linear models adjusted for baseline and time-varying confounders. The proportion of patients switching to a next therapy in the first 90 days post-index was compared between patients developing versus not developing TLS using Kaplan-Meier rates with log-rank P-value.Results: Among 6,343 patients with CLL/SLL, 71 (1.1%, mean age: 66.4 years, 26.8% females; 22 treated with venetoclax; mean [median] duration of the entire index regimen: 16.0 [10.0] months) developed TLS during the first 90 days of active treatment and 6,272 (98.9%, mean age: 65.9 years, 34.1% female; 170 treated with venetoclax; mean [median] duration of the entire index regimen: 22.0 [14.5] months) did not. Among all 6,343 patients, there were 1,129 TLS intervals and 138,429 non-TLS intervals observed post-index. All patients incurred considerable cumulative costs over the entire index regimen duration (TLS cohort: $201,200; non-TLS cohort: $158,590). Developing TLS was associated with 1.7 times more inpatient (IP) admissions (P<0.001; Fig. 1a), 2.0 times more days of IP stay (P=0.012), 22% fewer days of antineoplastic drug administration (P=0.020; Fig. 1a), and $3,062 PPPM higher healthcare costs (P=0.016), driven by significantly higher IP costs PPPM (MMCD=$1,688; P=0.044; Fig. 1b) vs. not developing TLS. Higher costs during TLS intervals were observed for patients initiated on a venetoclax-based regimen (TLS intervals: $24,170 PPPM; non-TLS intervals: $20,091 PPPM) and patients initiated on a non-venetoclax-based regimen (TLS intervals: $8,746 PPPM; non-TLS intervals: $6,915 PPPM). In the first 90 days post-index, HRU and costs were higher than when averaged over the entire duration of the index regimen, regardless of developing TLS or not (Table 1). Among patients not developing TLS, those treated with a venetoclax-based regimen had numerically higher cumulative TLS prevention costs during the first 90 days post-index ($4,398) than those treated with a non-venetoclax-based regimen ($2,879). Patients developing TLS switched more quickly to a next line of therapy in the first 90 days of treatment compared to those not developing TLS (12.6% vs. 5.1%, P=0.006; Table 2).Conclusions: In this study of CLL/SLL patients treated with CIT-, lenalidomide-, obinutuzumab-, or venetoclax-based regimens, TLS led to a significant HRU and cost burden (mostly driven by IP admissions) and a higher rate of treatment switching. Consideration of available treatment options based on patient goals and treatment expectations is warranted before selecting a treatment with a high risk of developing TLS. [Display omitted] DisclosuresRogers: AstraZeneca: Consultancy; Genentech: Consultancy, Research Funding; Innate Pharma: Consultancy; Pharmacyclics LLC: Consultancy; Janssen Pharmaceuticals, Inc: Research Funding; Acerta Pharma: Consultancy; AbbVie Inc.: Consultancy, Research Funding; ovartis Pharmaceuticals Corporation: Research Funding. Emond: GlaxoSmithKline: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy. Côté-Sergent: GlaxoSmithKline: Consultancy; Janssen: Consultancy. Kinkead: Janssen: Consultancy; Otsuka: Consultancy. Lafeuille: Pharmacyclics: Consultancy; Janssen Scientific Affairs, LLC: Consultancy; Pfizer: Consultancy; GlaxoSmithKline: Consultancy. Lefebvre: Pfizer: Consultancy; Pharmacyclics: Consultancy; Otsuka: Consultancy; Janssen Scientific Affairs, LLC: Consultancy; GlaxoSmithKline: Consultancy; Novartis: Consultancy; Regeneron: Consultancy. Huang: Johnson & Johnson: Current equity holder in publicly-traded company; Janssen Scientific Affairs, LLC: Current Employment.