Chemoimmunotherapy Research Articles

82P Multicenter analysis of neoadjuvant (chemo-)immunotherapy (C-IO) in stage IIB-IVB non-small cell lung cancer (NSCLC) resulting in curative surgery in routine clinical care (KOMPASS neo OP)

Background: Recent phase I and phase II trials report the feasibility of neoadjuvant C-IO prior to surgery. Furthermore, the studies report high pathological response rates which might be a surrogate marker for overall survival (OS).

80P Prospective analysis of patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant (chemo-) immunotherapy (C-IO) prior to resection or definitive radiochemotherapy (RCT) in routine clinical care (KOMPASS neo)

80P Prospective analysis of patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant (chemo-) immunotherapy (C-IO) prior to resection or definitive radiochemotherapy (RCT) in routine clinical care (KOMPASS neo)

128P A real-world scenario of applicability of immuno oncology agents into practice in NSCLC in a resource constrained setting

Background: Non-small cell lung cancer is one cancer which has seen radical change in treatment in the last decade with the advent of immunotherapy and targeted therapies. Chemo immunotherapy has increased the survival multi fold in metastatic setting and also in earlier lines and is the first line treatment now in non driver mutation setting. However, applicability of the same into real world practice has been dismal in low and middle income countries due to various reasons. Data is lacking in this setting.

Risk-adapted, ofatumumab-based chemoimmunotherapy and consolidation in treatment-naïve chronic lymphocytic leukemia: a phase 2 study

High-risk cytogenetics and minimal residual disease (MRD) after chemoimmunotherapy (CIT) predict unfavorable outcome in chronic lymphocytic leukemia (CLL). This phase 2 study investigated risk-adapted CIT in treatment-naïve CLL (NCT01145209). Patients with high-risk cytogenetics received induction with fludarabine, cyclophosphamide, and ofatumumab. Those without high-risk cytogenetics received fludarabine and ofatumumab. After induction, MRD positive (MRD+) patients received 4 doses of ofatumumab consolidation. MRD negative (MRD-) patients had no intervention. Of 28 evaluable for response, all responded to induction and 10 (36%) achieved MRD-. Two-year progression-free survival (PFS) was 71.4% (CI95, 56.5–90.3%). There was no significant difference in median PFS between the high-risk and the standard-risk groups. Ofatumumab consolidation didn’t convert MRD + to MRD-. In the MRD + group, we saw selective loss of CD20 antigens during therapy. In conclusion, risk-adapted CIT is feasible in treatment-naïve CLL. Ofatumumab consolidation didn’t improve depth of response in MRD + patients. Loss of targetable CD20 likely reduces efficacy of consolidation therapy.

Randomized controlled trial of individualized, low dose, fixed duration lenalidomide maintenance versus observation after frontline chemo-immunotherapy in CLL

Lenalidomide maintenance after frontline chemo-immunotherapy (CIT) in chronic lymphocytic leukemia (CLL) has not been standard due to the availability of novel therapies, though these remain out of reach for most in low-middle income countries. This single-center, open-label study randomized CLL patients (non-deletion 17p) after frontline therapy to lenalidomide maintenance (dose-escalated 2.5–10mg, 20/28 days per cycle for six months) or observation (2:1 allocation). Forty patients were included over 2018–2020. At a median follow-up of 22 months, median progression-free survival (PFS) with lenalidomide was not significantly different than observation (26 vs. 18 months, p = 0.4). Patients with minimal residual disease >10−2 had a trend toward better PFS with lenalidomide (19 vs. 7 months, p = 0.07). Grade 3 neutropenia was seen in 16.7% of patients on lenalidomide. Quality of life was comparable between the two arms. Low dose, fixed duration lenalidomide maintenance is not an effective strategy after frontline CIT in CLL.

Impact of Oral Targeted Therapy on the Economic Burden of Chronic Lymphocytic Leukemia in Canada.

Background: Continuous oral targeted therapy (OTT) for chronic lymphocytic leukemia (CLL) represents an effective therapy but also a major economic burden on the healthcare system. This study aimed to estimate future direct costs, along with the prevalence, of CLL in the era of continuous OTT in Canada. Methods: The economic burden of OTT was modelled and compared to chemoimmunotherapy (CIT), for CLL treatment. The burden was assessed/projected from 2011 to 2025. For the OTT scenario, CIT was considered the standard of care before 2015, while OTT was considered standard of care for patients with either unmutated immunoglobulin heavy-chain variable (IGHV) or del(17p)/TP53 mutations starting in 2015 and, from 2020 onwards, for all first-line treatments except for patients with mutated IGHV. A Markov model was developed including four health states: watchful-waiting, first-line treatment, relapse and death. Costs of therapy, follow-up/monitoring and adverse events were included. Key clinical parameters were extracted from pivotal clinical trials. Results: As incidence rates and rate of survival are increasing, the prevalence of CLL in Canada is projected to increase 1.8-fold, from 8301 patients in 2011 to 14,654 by 2025. Correspondingly, the total annual costs of CLL management are predicted to increase 15.7-fold, from $60.8 million to $957.5 million during that same period. Conclusions: Although OTT enhances survival for patients with CLL, it is nonetheless associated with an important economic burden due to the projected vast increase in costs from 2011 to 2025. Changes in clinical strategies, such as implementation of a fixed OTT treatment duration, could help alleviate financial burden.

Prediction of Treatment Efficacy in Relapsed Chronic Lymphocytic Leukemia

Background. The emergence of signaling pathway inhibitors (SPI) considerably improved the prognosis in relapsed chronic lymphocytic leukemia (R-CLL). Nevertheless, some patients cannot achieve optimal and sustained response. TP53 gene defects determine the refractoriness to immunochemotherapy (ICT) and lower rates of progression-free survival on SPI therapy. However, the prognostic value of complex karyotype (CK) in CLL has long been disputed. In recent years, greater attention has been placed on the prognostic impact of CK in the context of SPI therapy. Materials & Methods. The study included 180 patients who received the drug treatment for R-CLL (113 of them with ICT, 67 of them with SPI). Their age at the onset of second-line therapy, the response to first-line therapy, early (< 24 months) progression after first-line therapy, the number of therapy lines, and the presence of CK and TP53 gene defect were regarded as prognostic markers. Taking into account the clonal evolution in CLL, to assess the significance degree of the above predictors, Cox proportional hazards regression model with time-dependent variables was used. Results. The following independent factors proved to significantly reduce the risk of death: response achieved immediately after first-line therapy (hazard ratio [HR] 0.38; 95% confidence interval [95% CI] 0.20-0.72; p = 0.003) and the number of therapy lines (HR 0.56; 95% CI 0.37-0.86; p = 0.008). Treatment with only ICT in first and subsequent lines was associated with increasing risk of death (HR 2.25; 95% CI 1.09-4.63; p = 0.028). Genetic risks worsened the prognosis to a high degree of significance in the case of TP53 gene defect with excluded or unknown CK status (HR 10.54; 95% CI 4.25-26.17; p < 0.001) as well as in the case of CK (HR 14.08; 95% CI 5.77-34.35; p < 0.001). A significant predictor of poor outcome was reported to be the factor of unknown CK status without TP53 gene defect (HR 4.15; 95% CI 1.72-10.00; p = 0.002). Neither relapse time after first-line therapy nor the age > 65 years showed independent prognostic value. Conclusion. Standard karyotyping of peripheral lymphocytes with specific stimulation establishes a clearer disease prognosis and suggests the optimal choice of R-CLL treatment strategy.

Hronična limfocitna leukemija u ordinaciji opšte medicine

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, rarely affecting children. It is more common in males over 60. Etiopathogenetically, it represents an abnormal proliferation of lymphocytes in the bone marrow, which are dysfunctional although morphologically similar to mature ones. Case report: Female patient, 66, a housewife, comes for an examination due to fatigue lasting about a month and weight loss of 3-4 kg. She denies other health problems. On the examination, she is alert, oriented to time, space, and persons, eupnoeic, lymphadenopathy on the neck, axillae and groins. She gives away the impression of a patient with mild clinical symptoms. Clinical examination: clear breath sounds in all lung fields, regular heartbeat, clear tones, BP 140/80 mmHg, abdomen at chest level, painless to palpation, liver not palpable, and spleen palpated 2 cm below the costal arch. CBC (complete blood count) showed an increased number of leukocytes 181.30x109 /L and lymphocytosis 92.2%, other parameters were normal. She was referred to the hematologist in the Kraljevo General Hospital, where further diagnostics were performed. Blood count was repeated, Chest X-ray was performed, ultrasound (US) of the abdomen neck, axillae, groins, and heart, virology tests, ENT examination. Abdominal US showed a pathological finding with enlarged liver, spleen, lymph nodes (LN). ENT examination: enlarged tonsils, other findings unremarkable. Since chronic lymphocytic leukemia was suspected, she was referred to the Clinical Center of Serbia. Immunophenotyping (IF) and computed tomography (CT) of the neck, chest, and abdomen were performed. The diagnosis of CLL was confirmed. A Medical Council decided to perform immunochemotherapy (IHT) with fludarabine and rituximab. After 6 received cycles, the patient feels well and the CBC parameters are normal. Conclusion: CLL may be asymptomatic or nonspecific and with mild symptoms in a large number of patients. Therefore, blood tests with leukocytosis and absolute lymphocytosis findings are crucial to suspect the disease and perform further diagnostics.

EBV Associated Post-Transplant Lymphoproliferative Disorder Complicated with Haemophagocytic Lymphohistiocytosis After Allogeneic Stem Cell Transplant: A Rare Complication with Fatal Outcome

Epstein –Barr virus related post-transplant lymphoproliferative disorder is a fatal and life-threatening complication because of immunocompromised state.1 Haemophagocytic lymphohistiocytosis is a sign of poor outcome in EBV associated PTLD after allogeneic stem cell transplantation. It is particularly common when in vivo T cell depletion strategies have been applied.2 In both situations, post-transplant lymphoproliferative disorder and Haemophagocytic lymphohistiocytosis, infection with EBV is the key mechanism. Here I present a case of 29 years old female with acute myeloid leukaemia after second allogeneic stem cell transplant, who developed PTLD complicated with Haemophagocytic lymphohistiocytosis secondary to Epstein – Barr virus (EBV) infection. Patient was treated with chemo immunotherapy and responded but ultimately died after 100 days of transplant. The association of HLH and EBV related PTLD is rare and data on outcome of these patients are limited with very high mortality.

Standard treatment approaches for relapsed/refractory chronic lymphocytic leukemia after frontline chemoimmunotherapy.

Despite the effectiveness of chemoimmunotherapy (CIT), in most cases the clinical course of chronic lymphocytic leukemia (CLL) is characterized by consecutive episodes of disease progression and need for therapy. Treatment possibilities for patients with CLL in whom CIT fails whose disease progresses after initial CIT include pathway inhibitors (PIs) and, for selected patients, cellular therapy (ie, allogeneic stem cell transplant, chimeric antigen receptor T cells). PIs (ie, Bruton tyrosine kinase inhibitors, phosphatidylinositol 3-kinase inhibitors, and BCL2 inhibitors) are revolutionizing the treatment of CLL. PIs have proved to be more effective than CIT, both as upfront therapy and for relapsed/refractory disease, largely because they may overcome the negative impact of adverse biomarkers (eg, TP53 aberrations, unmutated IGHV) on outcomes and because of their acceptable toxicity. In this article, the management of patients with relapsed/refractory CLL is discussed, with a particular emphasis on the role of PIs.

Clinical Outcomes Among Real-World Patients with Chronic Lymphocytic Leukemia (CLL) Initiating First-Line Ibrutinib or Chemoimmunotherapy (CIT) Stratified By Risk Status: Results from a US Retrospective Chart Review Study

Clinical Outcomes Among Real-World Patients with Chronic Lymphocytic Leukemia (CLL) Initiating First-Line Ibrutinib or Chemoimmunotherapy (CIT) Stratified By Risk Status: Results from a US Retrospective Chart Review Study

Interim Positron Emission Tomography (iPET) Assessed Using Deauville Score for Patients with Follicular Lymphoma Receiving First-Line Chemoimmunotherapy

Interim Positron Emission Tomography (iPET) Assessed Using Deauville Score for Patients with Follicular Lymphoma Receiving First-Line Chemoimmunotherapy

A Cost-Effectiveness Analysis of Front-Line Treatment Strategies in Early Stage Follicular Lymphoma

Background: Radiation therapy (RT) has been considered the standard of care for front-line management for early-stage follicular lymphoma. Recent data suggests the use of RT is declining with more than half the patients receiving immunochemotherapy (ICT) with or without rituximab maintenance (RM). Cost-effectiveness analysis of these treatments has not been performed. Methods: We constructed a four-state partitioned survival model over a 15-year time horizon to compare RT alone, ICT and ICT+RM. The model was based on a real-world cohort of early-stage FL patients, staged using 18F-fluorodeoxyglucose positron emission tomography,from the Australasian Lymphoma Alliance. Lifetime direct health care costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated from an Australian tax-payer perspective. A pre-specified value of AUD $75,000 was defined as the willingness-to-pay (WTP) threshold reflecting recent approvals for therapeutics for indolent lymphoproliferative diseases in Australia. Results: Assuming 5% annual discounting the direct healthcare costs were: RT $14,480, ICT $22,171, ICT+RM $42,830 (Table 1). Compared with RT, ICT demonstrated an improvement in QALYs (+0.17) and an ICER of $44,879. Compared with RT, ICT+RM demonstrated a larger improvement in QALYs (+0.53) with an ICER of $53,062. Modelling a 25% cost reduction with a rituximab biosimilar led to further ICER reductions: ICT ($29,078); ICT+RM ($37,810). Conclusion: Although the initial healthcare-associated costs were higher than RT, over a 15-year horizon ICT and ICT+RM are cost-effective treatments in early stage FL from the Australian tax-payer perspective. Although the costs may differ internationally, the results remain broadly generalisable given the costs incurred related to time in the failure-free state. Table 1:Comparison of healthcare costs, quality-adjusted life-years and cost-effectiveness between front-line therapies in early stage FL Table 1 Disclosures Tobin: Gilead: Research Funding. Gandhi:Gilead Sciences: Honoraria; Mater Research: Current Employment; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Other: Travel, accommodation, expenses ; Genentech: Honoraria; Amgen: Honoraria; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding. Mollee:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees.

Real-World Prognostic Biomarker Testing, Treatment Patterns and Dosing Among 1461 Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) from the informCLL Prospective Observational Registry

Real-World Prognostic Biomarker Testing, Treatment Patterns and Dosing Among 1461 Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) from the informCLL Prospective Observational Registry

Clonal Somatic Mutations Are a Biomarker for Inferior Prognosis in Diffuse Large B-Cell Lymphoma

Background Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma subtype with a 5-year survival of ~64%. While DLBCL is treated using immunochemotherapy (IC) with curative intent, 20%-40% of patients do not reach remission or relapse post IC. Clonal somatic mutations have been associated with aging, hematologic malignancies (predominately myeloid), and reduced OS in the general population. The objective of this study was to evaluate the association of clonal somatic mutations with event-free survival (EFS) and overall survival (OS). Methods We studied newly diagnosed DLBCL cases treated with IC who were enrolled in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). Clinical and treatment data were abstracted from medical records and all patients were systematically followed for disease outcomes. Pre-treatment DNA was extracted from matched peripheral blood and paraffin-embedded tumor tissue, and whole exome sequencing was conducted at 100x coverage. From the peripheral blood, allele counts from GVCF files produced by HaplotypeCaller in GATK were extracted for 42 genes commonly associated with clonal hematopoiesis (e.g. DNMT3A, TET2, and ASXL1). Mutations were deemed clonal somatic if the population minor allele frequency was <0.5% in ExAC and had a variant allele fraction (VAF) that deviated from 0.5 using a binomial distribution test at p<0.001. Furthermore, mutations had to have a minimum alternate read count of at least 5 reads, a VAF greater than or equal to 10%, and met at least one of the following criteria: CAVA impact of "HIGH"; pathogenic/likely pathogenic per ClinVar; or reported in COSMIC at least 10 times. EFS was defined as time from diagnosis to disease progression, relapse, retreatment, or death due to any cause. The association of clonal somatic mutations with prognosis was estimated using Kaplan-Meier curves, and hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression. Associations were adjusted for age at diagnosis, sex, and the International Prognostic Index (IPI). Results The study consisted of 261 DLBCL patients treated with IC. The median age at diagnosis was 65 years (range 20-90) and 56% were male. With a median follow-up time of 5.1 years (range 0.1-15.0), there were 100 events and 80 deaths. A total of 17 (6.5%) patients had clonal somatic mutations, and16 patients were over the age of 60. A total of 8 (of 42) genes had clonal somatic mutations, with SF3B1, ASXL1, and TET2, being the most frequent (4 individuals per gene). VAFs ranged from 0.10 to 0.28 and none of the patients had multiple mutations. Additionally, the clonal somatic variants found in the peripheral blood were abscent in the tumor sample. Of the 17 patients with clonal somatic mutations, 12 had an event while 88 patients without a mutation had an event. In a univariate analysis, clonal somatic mutations were associated with inferior EFS (HR=2.55, 95% CI 1.39-4.68, p=0.002; Figure 1A). After adjusting for age, sex, and IPI, clonal somatic mutations remained associated with inferior EFS (HR=2.02, 95% CI 1.09-3.74, p=0.026). Clonal somatic mutations were also associated with inferior OS in the univariate analysis (HR=2.06, 95% CI 0.99-4.29, p=0.053), which attenuated after multivariate adjustment (HR=1.59, 95% CI: 0.76-3.34, p=0.22, Figure 1B). Although based on small numbers, mutations in SF3B1 were associated with inferior EFS (HR=3.25, 95% CI 1.16-9.12, p=0.025), but did not reach significance for OS (HR=2.56, 95% CI 0.78-8.38, p=0.120). Conclusions In this novel study of newly diagnosed DLBCL patients, clonal somatic mutations were identified in 6.5% of patients and were associated with inferior outcomes. Additional research is required at deeper sequencing to validate these findings and integration with tumor genomics is required to understand the prognosis of DLBCL patients with smaller clonal populations. Disclosures Shah: Dren Bio: Consultancy. Maurer:Celgene / BMS: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding. Martin:Celgene: Consultancy; Karyopharm: Consultancy, Research Funding; Morphosys: Consultancy; Regeneron: Consultancy; Incyte: Consultancy; Kite: Consultancy; Cellectar: Consultancy; Bayer: Consultancy; Beigene: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Janssen: Consultancy; Teneobio: Consultancy. Witzig:AbbVie: Consultancy; Incyte: Consultancy; Acerta: Research Funding; Karyopharm Therapeutics: Research Funding; Immune Design: Research Funding; Spectrum: Consultancy; Celgene: Consultancy, Research Funding; MorphSys: Consultancy. Nowakowski:NanoString: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Kymera: Consultancy; Kite: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees; MorphoSys: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding. Novak:Celgene/BMS: Research Funding. Cerhan:NanoString: Research Funding; BMS/Celgene: Research Funding.

Outcomes of First-Line Ibrutinib in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and High-Risk Genomic Features with up to 6.5 Years Follow-up: Integrated Analysis of Two Phase 3 Studies (RESONATE-2 and iLLUMINATE)

Outcomes of First-Line Ibrutinib in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and High-Risk Genomic Features with up to 6.5 Years Follow-up: Integrated Analysis of Two Phase 3 Studies (RESONATE-2 and iLLUMINATE)

Safety and Antitumor Activity Study Evaluating Loncastuximab Tesirine and Rituximab Versus Immunochemotherapy in Diffuse Large B-Cell Lymphoma

Introduction: Patients with diffuse large B-cell lymphoma (DLBCL) who fail immunochemotherapy (IC) and are unsuitable for autologous stem cell transplantation (ASCT) and those who relapse shortly after ASCT have extremely poor prognosis and need additional treatment options. Loncastuximab tesirine (Lonca) is an antibody-drug conjugate (ADC) composed of a humanized anti-CD19 antibody conjugated to a pyrrolobenzodiazepine dimer toxin. In a Phase 2 study (NCT03589469), Lonca demonstrated single-agent antitumor activity with manageable toxicity in patients with relapsed/refractory (R/R) DLBCL. Rituximab is a CD20-targeting monoclonal antibody used in front-line IC for DLBCL and in salvage regimens, such as rituximab/gemcitabine/oxaliplatin (R-GemOx). The addition of rituximab to a CD19-targeting pyrrolobenzodiazepine ADC appears to prolong tumor control in preclinical studies, providing the rationale for evaluating Lonca combined with rituximab (Lonca-R) as a treatment for R/R DLBCL. Study Design and Methods: This is a Phase 3, randomized, open-label, 2-part, 2-arm, multicenter study of Lonca-R versus standard IC in patients with R/R DLBCL (NCT04384484). Part 1 is a nonrandomized safety run-in with Lonca-R. The toxicity of Lonca-R will be compared with previous single-agent Lonca safety data after 20 patients have completed Cycle 1 in Part 1. Provided no significant increase in toxicity is observed, Part 2 will be initiated. Part 2 is a randomized study of Lonca-R versus R-GemOx (Figure 1). Key inclusion and exclusion criteria are reported in Table 1. The primary objective of Part 2 is to evaluate the efficacy of Lonca-R versus R-GemOx, using progression-free survival (PFS) as the primary endpoint. PFS will be defined as the time between randomization and first documentation of recurrence, disease progression or death (central review) and the primary analysis will compare PFS between treatment arms using stratified log-rank testing. Secondary objectives include evaluation of safety, pharmacokinetics, and immunogenicity of the combination, in addition to the impact of treatment on symptoms, patient-reported outcomes and patients' overall health. In Part 1 and in the Lonca-R arm of Part 2, patients will receive intravenous (iv) Lonca at 150 µg/kg on day 1 of each 21-day cycle for 2 cycles, then at 75 µg/kg on day 1 for up to 6 additional cycles. Rituximab 375 mg/m2 iv will be administered subsequent to Lonca infusion on day 1 of each cycle. Patients treated with Lonca-R will also be given dexamethasone 4 mg (oral, twice a day), where not contraindicated, on the day before, the day of, and the day after Lonca-R infusion. In the R-GemOx arm, patients will receive rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatin 100 mg/m2 iv on day 1 of each 14-day cycle up to a total of 8 cycles. Patients will receive premedication and supportive care according to the respective prescribing information for rituximab, gemcitabine, and oxaliplatin. The trial is planned to open in Q3/Q4 2020, and target enrollment is 350 patients. Funding: This study is sponsored by ADC Therapeutics SA; https://clinicaltrials.gov/ct2/show/NCT04384484. Disclosures Linhares: Jazz Pharmaceuticals: Consultancy; ADC Therapeutics, Verastem Oncology, Bristol Myers-Squibb (Juno), AstraZeneca: Research Funding; Miami Cancer Institute, Baptist Health South Florida: Current Employment. Gandhi:TG Therapeutics (Advisory board), GlaxoSmithKline (Advisory board): Membership on an entity's Board of Directors or advisory committees. Adeleye:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Ungar:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Hamadani:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme, AstraZeneca: Speakers Bureau; Janssen R&D; Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio: Consultancy; Takeda Pharmaceutical Company; Spectrum Pharmaceuticals; Astellas Pharma: Research Funding. OffLabel Disclosure: Rituximab is licensed for treatment of NHL but is being used in combination with an unlicensed drug (loncastuximab tesirine) in this study

Comparative Efficacy of First-Line Chemotherapy-Free Combinations in Chronic Lymphocytic Leukemia (CLL): A Network Meta-Analysis

Introduction: Chronic Lymphocytic Leukemia (CLL) is an incurable B-cell malignancy which disproportionately affects the elderly. Although first-line chemoimmunotherapy (CIT) improved CLL clinical outcomes, recent randomized trials revealed superior outcomes with novel chemotherapy-free combinations (CFC) incorporating anti-CD20 monoclonal antibodies and inhibitors of BTK or Bcl-2. So far, these CFC have not been compared head-to-head. We conducted this network meta-analysis to evaluate their relative efficacy to each other. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of CLL; trials that explored the efficacy of first-line CFC with Obinutuzumab (O), Rituximab (R), Ibrutinib (IB), Acalabrutinib (ACAL), Venetoclax (VEN) compared to standard CIT that included Chlorambucil (CHLOR) with either R or O, Bendamustine+Rituximab, or Fludarabine+ Cyclophosphamide+R; and phase 3 randomized studies reporting responses, progression, death, and adverse (AE) events. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Five studies comprising a total of 2,272 participants were included. When O-based CFC data was analyzed, only ACAL-O had a significant lower relative risk (RR) of progression and death (P&D). There were no significant differences with respect to overall response rates (ORR), complete remission (CR), minimal residual disease (MRD), or grade >3 adverse events (Grd3+) among O-based CFC. When R-based CFC data was analyzed, IB and IB-R were not different with respect to RR of P&D, ORR, CR, MRD, or Grd3+. When the data was analyzed as CFC versus combined CIT, only ACAL-O was found to be significantly superior to other O- and R-based CFC with respect to RR of P&D. ORR and Grad3+ rates of O- and R-based CFC were not significantly different. While ACAL-O, IB-O, and VEN-O had superior CR and MRD rates compared to other CFC, there were no significant differences among each other. Conclusions: This network meta-analysis is the first to compare and rank first-line CFC therapies in CLL. It indicates that ACAL-O has a superior profile having the lowest RR of P&D without significant difference in Grd3+ among CFC. Disclosures No relevant conflicts of interest to declare.

Severe Infections in Patients with Chronic Lymphocytic Leukemia Treated with (Immuno-)Chemotherapy: A Pooled Analysis of Gcllsg Trials

Severe Infections in Patients with Chronic Lymphocytic Leukemia Treated with (Immuno-)Chemotherapy: A Pooled Analysis of Gcllsg Trials

Characteristics and Treatment Patterns of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Who Received ≥3 Lines of Therapies

Introduction: Treatment options continued to evolve in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with many novel treatments available in recent years. The current study aimed to describe characteristics and treatment patterns of patients with R/R DLBCL who received ≥3 lines of therapy (LOT) using recent real-world data. Methods: This study used the PharMetrics Plus administrative claims database to identify adult patients who had ≥1 inpatient claim or ≥2 outpatient claims for DLBCL (ICD-10: C83.3) between 10/01/2015 and 09/30/2019. Patients were selected if they had ≥6-months of continuous eligibility before the first DLBCL diagnosis (index diagnosis). To capture newly diagnosed patients, the study excluded patients who had a claim for a possible DLBCL diagnosis and other hematologic malignancies (except hematologic conditions that may transform into DLBCL) before the index diagnosis and those who had stem cell transplantation (SCT) as the first treatment without prior chemotherapy (CT). An algorithm was developed to define LOT. In general, a new LOT was indicated by addition of a new drug or re-initiation of the previous LOT after a gap of ≥90 days. Pharmacologic therapies were categorized as CT or chemoimmunotherapy (CIT) or novel agent-based therapy (including brentuximab vedotin, ibrutinib, venetoclax, lenalidomide, obinutuzumab, nivolumab and pembrolizumab). SCT was counted as consolidation therapy instead of a separate line, while chimeric antigen receptor T cells (CAR-T) was counted as a separate line with preparation included (e.g., leukapheresis, bridging therapy, and lymphodepletion). Patients who received a third LOT (3L) comprised the study population, with the index date defined as the initiation date of 3L pharmacologic therapy or the infusion date of 3L SCT or CAR-T. 3L treatment distribution was described separately before and after the first CAR-T approval for DLBCL (10/18/2017). Treatment duration of 3L pharmacologic therapies was analyzed using Kaplan-Meier (KM) analysis. The proportion of patients initiating 4L during the observed follow-up period were described for all patients receiving a 3L. Due to the limited follow-up time and a high proportion of censoring, the current data was not mature to estimate rates of 4L initiation at different time points based on the KM analysis. All analyses were conducted for the overall study population and by treatment. Results: Among the 3,559 DLBCL patients receiving ≥1L treatment, 92.3% were treated with rituximab-containing regimens and 68.9% with R-CHOP or similar in 1L. There were 160 (4.5%) patients who received ≥3 LOT, with a mean age of 58.5 years and 64.4% male. Before CAR-T approval, 51 patients received 3L: 52.9% received CT/CIT, 33.3% received novel agent-based therapy, and 13.7% received SCT. After CAR-T approval, 109 patients received 3L: 45.9%, 30.3%, 7.3%, and 16.5% received CT/CIT, novel agent-based therapy, SCT and CAR-T, respectively. There were some differences in patient characteristics across treatment groups. Specifically, CAR-T patients had a relatively lower mean Charlson Comorbidity Index (CCI) score (2.9). The novel therapy group had a shorter median time from index diagnosis to index date (10.3 months). SCT patients were younger (mean 56.6 years) but with a relatively higher mean CCI score (4.2). The median follow-up time was 5.0 months and varied across treatments: from 3.9 months for CAR-T to 5.7 months for SCT. Among patients receiving pharmacologic treatments, the median treatment duration was 3.1 months and 2.8 months for the CT/CIT and novel agent-based therapy groups, respectively. During a median follow-up time of <6 months, a total of 51 (31.9%) patients initiated 4L. The proportion was 27.8% in the CAR-T group, 28.6% in the CT/CIT group, 38.0% in the novel therapy group and 33.3% in the SCT group. Conclusions: In patients with R/R DLBCL receiving 3L treatment post CAR-T approval, about 76% were treated with CT/CIT or novel agent-based therapies, though most of the novel agents are not indicated for DLBCL. CAR-T and SCT were used in 17% and 7% of patients, respectively. Treatment duration of 3L CT/CIT or novel agent-based therapies was short. A relatively high proportion of patients moved to the next LOT during a short follow-up period. These findings highlight the unmet need for more effective treatments among R/R DLBCL patients in 3L and later lines. Disclosures Xie: Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Wu:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liao:ADCT: Current Employment, Current equity holder in publicly-traded company. Du:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Noman:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liang:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Camardo:ADCT: Current Employment, Current equity holder in publicly-traded company. Chen:ADCT: Current Employment, Current equity holder in publicly-traded company.