Median Lines Of Therapy Research Articles

The time toxicity efficacy-effectiveness gap: A population-based study of stage III/IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

133 Background: While patients enrolled in clinical trials tend to have superior cancer-specific outcomes relative to those in routine practice (the ‘’efficacy-effectiveness gap’’), it is unknown if this gap extends to time toxicity. While trial protocols can impose additional contact days, trial participants also tend to be healthier, perhaps needing fewer contact days. We sought to evaluate the time toxicity efficacy-effectiveness gap among patients with stage III/IV NSCLC. Methods: We created a population-based, retrospective cohort with health administrative data covering the population of Ontario, Canada (15.5 million), of adults aged ≥20 years diagnosed with stage III/IV NSCLC in 2014-2017 and died in 2014-2019, receiving palliative systemic anti-cancer drug(s) as part of a trial. We matched patients 1:1 to those who received the same drug(s) in the real world (post-approval) in the same line of treatment, and received the same total lines of therapy. We calculated contact days (days with healthcare contact outside the home) from diagnosis to death and measured overall survival. We plotted, normalized, and fitted with cubic splines the weekly percentage of contact days to obtain trajectories over the disease course. Results: We identified and matched 55 trial participants to 55 patients in routine practice. Trial participants were younger (median age, 62 vs 66 years), had fewer co-morbidities (hypertension, 35% vs 53%), and more often had de novo metastatic disease (82% vs 67%). Median lines of therapy were 2. Systemic therapy regimens most commonly included immunotherapy (n=41, 75%). Trial participants initiated systemic therapy sooner than in routine practice (median 2.0 vs 2.4 months). Trial participants had a longer overall survival (median 13.8 vs 11.6 months) and a similar number of contact days (median 79 vs 78 days). The percentage of contact days was lower in trial participants due to longer survival (median 19% vs 22%). Trial participants had similar acute/assisted institutional care contact days (median 19 vs 18 days), but more days with laboratory tests (median 23 vs 17 days), systemic therapy (median 9 vs 6 days), and radiotherapy visits (median 15 vs 11 days). Normalized trajectories for both cohorts followed a ‘’U-shape’’; the difference between the maximal peak and trough was smaller in trial participants. Conclusions: We describe a novel efficacy-effectiveness gap in time toxicity, in addition to the previously established efficacy-effectiveness gap in overall survival. Encouragingly, trial participants did not experience delays in treatment, and initiated treatments sooner than in routine practice. Among trial participants, the higher number of contact days for tests, and the shallower U-shaped curve (indicating frequent visits even when relatively well) indicate potential opportunities to decrease trial-related time toxicity.

Exploring T cell subsets as predictors of response to BCMA targeting bispecific antibody therapy in multiple myeloma.

7567 Background: BCMA targeting bispecific Antibody (bsAb) therapy has shown unprecedented response and survival rates in patients with relapsed/refractory multiple myeloma (MM). The clinical activity of bsAb therapy has been shown to depend on T-cell function, yet clinical parameters, such as absolute lymphocyte count (ALC) have not been found to be associated with response to bsAbs. The aim of the present study was to elucidate whether distinct T cell subsets, such as CD4 and CD8 counts as well as their proportion within the ALC are associated with outcome of BCMA targeting bsAb therapy. Methods: We retrospectively collected data on 79 patients who had been treated with at least one full dose of a BCMA targeting bsAb. T cell subsets, including ALC, total CD3, CD4 and CD8, were measured from peripheral blood within 7 days prior to bsAb therapy initiation. Statistical analysis was performed with SAS version 9.4 using univariate and multivariate logistic regression models. Results: Median age of the patient cohort was 72 (31-84) years with 40/79 (51%) being male and 15/79 (19%) being African American. Median lines of therapy was 5 (2-12) with 78/79 (99%) patients being triple class refractory and 50/79 (63%) being penta-drug refractory. 59/79 (75%) of patients had at least one prior stem cell transplant (SCT) with 35/79 (44%) having had at least two SCTs. 26/79 (33%) patients had prior exposure to BCMA targeting therapy, with 18/79 (23%) and 8/79 (10%) previously having received belantamab mafodotin or BCMA targeting Car-T cell therapy respectively. Cytokine release syndrome (CRS) occurred in 38/79 (48%) of patients with the majority (92%) being grade 1 with the remainder being grade 2. Median ALC was 1.02 (0.25-5) x103/mL, median CD4 count was 0.27 (0.04-1.13) x103/mL while median CD8 count was 0.5 (0.07-2.97) x103/mL. Overall response (OR) rate of the whole cohort was 82% (69/79) with best responders (³very good partial response) comprising 51% (40/79). While total ALC, CD4 and CD8 counts did not appear to impact response to BCMA targeting bsAb therapy, the ratio of CD4 to ALC proved to be significantly associated with OR (univariate p=0.04) and best response (univariate p= 0.004, multivariate p=0.01) . The CD8 to ALC ratio had no significant impact in this patient population. The only other factor to show a significant association with response was the number of prior lines of therapy with higher numbers being associated with worse response (p=0.046). Conclusions: Our study suggests that an increased proportion of CD4 cells within the ALC is significantly associated with better response to BCMA targeting bsAb. While future studies are needed to elaborate on CD4 function in bsAB therapy, our findings imply that therapeutic strategies to increase the CD4 proportion could lead to improved bsAb therapy effectiveness.

Bisantrene in Combination with Fludarabine and Clofarabine As Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)- an Open-Label, Phase II, Study

Background: Bisantrene (Bis), is a topoisomerase-II inhibitor with anthracycline-like activity, lower cardiotoxicity, and activity in patients (pts) with relapsed (rel)/primary refractory (PR) acute myeloid leukemia (AML) (Am J Hematol, 2021). Bis was also found to synergize with the cytotoxic purine nucleoside analogs clofarabine (Clo) and fludarabine (Flu) in vitro (J Clin Exp Oncol, 2021). We now conducted a phase II study combining Bis with Clo and Flu in pts with Rel/PR AML (NCT04989335). Methods: This was a phase II open-label single-center study with 2 stages: a stage with 3+3 dose escalation to assess the safety and provide phase 2 dose (RP2D, 4 vs 5 days) of infusion (i.v.) with up to 12 pts and an expansion phase with up to 17 pts (Simon 2-stage design 9+8) to assess the primary efficacy and confirm the safety of f Bis/Clo/Flu combination pts with Rel/PR AML. Flu (10 mg/m 2) was administered i.v. over 1 hour (h), followed by a 1-h infusion of Clo (30 mg/m 2), and then a 2-h infusion of Bis at 250 mg/m 2, with a 1-hour break for 4 days. The primary endpoint was achieving a partial response (PR). Efficacy was assessed by bone marrow (BM) examination 21 - 30 days post-therapy. Safety included treatment-emergent adverse events (TEAEs), all-cause mortality, and cardiac monitoring with ECG and troponins Toxicity was assessed as per Common Terminology Criteria for Adverse Events (CTCAE v5.0). Interim analysis was planned after the first 12 pts. Results: 20 pts were included from August 2021. The median age was 48 (19-69) years and 55% were male.14 pts had de novo AML and 5 had secondary AML, 11 pts were in rel, while 9 had PR disease. Median lines of therapy were 4(3-9), 12 with ≤ 4 and 8 >4 lines of therapy. All pts were refractory to the last line of therapy.15 pts (75%) were in relapse post allogeneic transplantation (HSCT). 5 (25%) pts had active extramedullary disease (EMD, 1 with CNS involvement). Median bone marrow blasts pre-Bis/Clo/Flu treatment was 50%. Cytogenetic was normal in 10 (50%) of the pts, 5 had a complex karyotype, 2 MLL rearrangements, 1 t8; 21 and 2 pts had other chromosomal abnormalities. The maximum tolerated dose of the Bis/Clo/Flu combination was 4 days of infusion due to grade 3 liver toxicity in 2 pts and 1 pt that died from sepsis in the first stage of the study. Overall 10 pts developed liver toxicity with elevated liver enzymes and bilirubin in 9 of them (grade 1-4 pts; grade 2-3 pts and grade 3-3 pts). Liver toxicity was transient and resolved in all pts. Two pts had treatment interruption due to liver toxicity. 4 pts had grade I renal toxicity, 7 had mild fluid retention, and 18 developed neutropenic fever of which 10 pts had verified bacteremia. Five pts had pneumonia, 4 invasive fungal infections, and 2 sepsis (1/2 died).1 additional pt died from cerebral venous sinus thrombosis. Overall 5 pts died early and could not be evaluated for response. Clinical-relevant cardiac toxicity was not observed in any of the pts and no one developed ECG changes Transient grade 1 elevation of troponin levels was observed in 4 pts. Six pts responded (CR-5, PR-1) 3 with EMD, however, responses were short-lived and lasted up to 3 months. Five pts (responding-4, active disease-1, being the second transplant in 4) underwent HSCT 1-3 months post-Bis/Clo/Flu with reduced /intermediate intensity conditioning. Stem cell donors were haploidentical-2, matched unrelated -1, and matched sibling-2, respectively. Three pts died: one from graft versus host disease and the other from relapse within 4 months post-transplant and the third from sepsis 2 years post-HSCT. Two of the transplanted pts are in complete remission with a 2-month follow-up. Conclusions : In this Phase II study in a very advanced group of relapsed refractory AML ptsresistant to multiple previous lines of chemotherapy including transplantation and with a median of 50% blasts at study initiation, Bis/Clo/Flu combination therapy was found to be safe and well tolerated without cardiac toxicity or tumor lysis syndrome. The maximum length of Bis/Clo/Flu administration was 4 days due to rapidly reversible liver toxicity, and transaminitis. As expected in this highly pretreated population, the infection rates were high. Six /15 evaluable pts (40%) respond, enabling an HSCT in 5 of them. These rather impressive results in such a heavily pretreated population support further studies of Bisantrene-based combinations, including those with venetoclax or hypomethylating agents.

P17.06.B TARGETED THERAPY MATCHED TO GENOMIC ALTERATIONS (BRAFV600E, NTRK, FGFR, ROS1, PIK3CA, PTEN) IN PATIENTS WITH RECURRENT IDH WILDTYPE GLIOBLASTOMA: A REAL-LIFE COHORT ANALYSIS FROM VENETO INSTITUTE OF ONCOLOGY, PADUA (ITALY)

Abstract BACKGROUND The use of next-generation sequencing (NGS) allows the identification of subgroups of patients that may respond to personalized targeted therapies (TT). Despite the acquired deep knowledge about biology, there are only a few data available regarding TT efficacy and feasibility for patients with glioblastoma (GBM). MATERIAL AND METHODS We retrospectively analyzed a cohort of patients with recurrent GBM treated at Veneto Institute of Oncology, Padua (Italy) with TT based on their individual NGS profile. NGS was obtained with FoundationOne®CDx on formalin-fixed paraffin-embedded (FFPE) tissue samples. We identified 6 druggable genomic alterations, classified according to ESCAT (ESMO Scale for Clinical Actionability of molecular Targets): BRAFV600E mutation (IB), NTRK1-2-3 fusions (IC), FGFR1-2-3 alterations (IIB), ROS1 fusions (IIIA), PIK3CA mutations (IIIA) and PTEN loss/mutations (IIIA). TT was given as agnostic approval, part of compassionate use programs or in clinical trials. Response assessment was based on RANO (Response Assessment in Neuro-Oncology) criteria. RESULTS Between March 2020 and December 2022, 34 patients with recurrent glioblastoma received TT (19 males, 15 females, median age of 54 years at time of TT initiation). ECOG PS was 0-1 in 29 pts. All patients received radiotherapy and temozolomide as first-line therapy. The median line of therapy with TT was 3 (range 2-7). TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts). At data cut-off (March 2023), 19 patients had died. In the entire cohort, median overall survival and progression-free survival (PFS) after starting TT was 8.72 and 2.14 months, respectively. The dabrafenib/trametinib subgroup had the longest median PFS (5.23 months), a disease control rate (DCR) of 77%, an objective response rate of 22%, and a median duration of response of 22.5 months. 7/9 pt had died and 2 pts are continuing dabrafenib/trametinib. The pt with ROS1-GOCP fusion maintained a complete response for 12 months with entrectinib. Among the others, no complete/partial responses were detected. DCR due to stable disease was 50% in larotrectinib and erdafitinib, 8.3% in ipatasertib+/-atezolizumab, 0% in alpelisib subgroup. No toxicities were reported in dabrafenib/trametinib subgroup. Among all patients, no grade 4 drug-related adverse events were observed and in any case TT was interrupted for toxicity. CONCLUSION Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest deeper explorations in targeting ROS1 and FGFR. Further correlation among patients' outcome, molecular characteristics and TT timing are still under investigation.

SYST-20 TARGETED THERAPY MATCHED TO GENOMIC ALTERATIONS (BRAFV600E, NTRK, FGFR, ROS1, PIK3CA, PTEN) IN PATIENTS WITH RECURRENT IDH WILDTYPE GLIOBLASTOMA: A REAL-LIFE COHORT ANALYSIS FROM VENETO INSTITUTE OF ONCOLOGY, PADUA (ITALY)

Abstract We retrospectively analyzed 34 patients (pts) [19 males, 15 females, median age 54] with recurrent IDH wildtype glioblastoma treated with target therapy (TT) based on their next-generation sequencing (NGS) profile, between March2020 and December2022 at Veneto Institute of Oncology, Padua (Italy). ECOG PS was 0-1 in 29 pts. All pts received previous radiotherapy and temozolomide. NGS was obtained with FoundationOne®CDx on formalin-fixed paraffin-embedded samples. We identified 6 druggable genomic alterations, classified according to ESCAT (ESMO Scale for Clinical Actionability of molecular Targets): BRAFV600E mutation (IB), NTRK1-2-3 fusions (IC), FGFR1-2-3 alterations (IIB), ROS1 fusions (IIIA), PIK3CA mutations (IIIA) and PTEN loss/mutations (IIIA). The median line of therapy with TT was 3 (range 2-7). TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts). At data cut-off (March2023), 19 patients had died. In the entire cohort, median overall survival and progression-free survival (PFS) after starting TT was 8.72 and 2.14 months, respectively. The dabrafenib/trametinib subgroup had the longest median PFS (5.23 months), a disease control rate (DCR) of 77%, an objective response rate of 22%, and a median duration of response of 22.5 months. 7/9 pt had died and 2 pts are continuing dabrafenib/trametinib. The pt with ROS1-GOCP fusion maintained a complete response for 12 months with entrectinib. Among the others, no complete/partial responses were detected. DCR due to stable disease was 50% in larotrectinib and erdafitinib subgroups and 8.3% in ipatasertib+/-atezolizumab subgroup. No toxicities were reported in dabrafenib/trametinib subgroup. Among all patients, no grade 4 drug-related adverse events were observed and in any case TT was interrupted for toxicity. Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest further explorations in targeting ROS1 and FGFR.

Real world evidence for continuing HER2-directed therapy for metastatic breast cancer.

e18623 Background: Continuing HER2-directed therapy in metastatic breast cancer (MBC) beyond first line has been demonstrated to improve progression free survival (PFS) and overall survival (OS) in many randomized studies. Due to cost, many publicly funded health care systems restrict public funding to 2 lines of HER2 directed therapy (HER2Rx) in MBC. The purpose of this study is to assess the proportion of patients with HER2 positive MBC who were eligible to receive systemic therapy beyond second-line and successfully accessed continued HER2Rx despite lack of public funding. We also analyzed how the ability to access continued HER2Rx impacts survival. Methods: The BC Cancer Breast Cancer Outcomes Unit collects clinical, pathological and outcome data on patients diagnosed within BC. In addition, all publically funded anti-neoplastic therapy is recorded in the BC Cancer pharmacy database. These 2 databases were cross-referenced to identify patients who received any HER2Rx for MBC between 2013 and 2018, in the era where trastuzumab plus pertuzumab and TDM-1 were standard, publically available options. The number of lines of therapy received, treatment choice, and fitness to continue therapy beyond 2 lines were analyzed by manual chart review. Survival data was analyzed. Results: 571 patients met inclusion criteria. Median follow up was 47.6 months. Overall, 267 (47%) patients were eligible to continue therapy beyond second-line. Of these, 210 (37% of the whole cohort) accessed continued HER2-directed therapy, while 57 (10%) were eligible but unable to access continued HER2Rx. Of the remaining 304 patients in the total cohort, 110 patients (19%) had stable disease on continued first- or second-line therapy and 194 patients (34%) had deteriorating status precluding further treatment beyond second-line. The median lines of therapy in the entire study population was 3 (range 1-12). Median number of cycles of HER2-directed therapy received beyond second-line for those eligible to continue was 18 cycles. Median OS for those who continued HER2Rx was 59.7 months compared to 31.4 months for those who were eligible but unable to access continued HER2Rx; HR 0.42 (95% CI 0.31-0.58, p < 0.001). The vast majority of patients who continued to access HER2Rx did so through clinical trial or patient assistance programs, very rarely through private health insurance or out-of-pocket expenditures. Conclusions: Nearly half of patients with HER2 positive MBC were eligible to receive more than 2 lines of HER2 directed therapy. The majority of eligible patients do ultimately secure access despite prohibitive public funding policies. Receiving further HER2Rx was associated with a significant and clinically meaningful OS benefit of 28 months over those who go on to receive non-HER2 directed therapy. This survival advantage provides real-world evidence in support of the urgent need for more permissive public funding of HER2 directed therapy for MBC.

Outcomes of Patients With Classic Hodgkin Lymphoma Who Relapsed After Autologous Stem Cell Transplant.

Immune checkpoint inhibitors (ICIs) and brentuximab vedotin (BV) are novel agents for classic Hodgkin lymphoma, including relapse after autologous stem cell transplant (ASCT). However, their impact on survival post-ASCT relapse, in comparison with conventional therapy, is less known due to the lack of randomized controlled trials. Clinical characteristics and outcomes of 115 patients with relapse (or progression) after ASCT are studied. After a median follow-up of 8.59 years from post-ASCT relapse, the median progression-free survival (PFS) and overall survival (OS) were 0.91 and 5.07 years, respectively. Median lines of therapy after post-ASCT relapse was 2 (range, 1-12). The median PFS was not reached (NR) versus 1.11 versus 0.50 versus 0.85 versus 0.78 years (P = 0.006) and OS was NR versus 7.60 versus 3.08 versus 3.51 versus 3.17 years (P = 0.28) in patients first treated with ICIs versus BV versus investigational agents versus chemotherapy versus radiation therapy (RT). First-line treatment with novel agents (ie, ICIs and BV) was associated with superior outcomes compared with investigational agents and chemotherapy/RT with a median PFS of 1.65 versus 0.50 versus 0.79 years (P = 0.003) and a median OS of 7.60 versus 3.08 versus 3.32 years (P = 0.08). Regardless of lines of therapy, the treatment with ICIs had the most favorable outcome with a median PFS and OS of 3.98 and NR years, respectively. Allogeneic stem cell transplant (allo-SCT) was done in 23 patients (20%), and the median post-allo-SCT PFS and OS were 1.31 and 2.35 years, respectively. In conclusion, survival following post-ASCT relapse improves significantly when patients receive novel agents.

Proteomic Profiles of Cytokine Release Syndromes Following Lisocabtagene Maraleucel and Idecabtagene Vicleucel

Introduction: Adoptive cell therapy with chimeric antigen receptor (CAR) T-cells has improved responses in refractory diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Most CAR-T recipients experience cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) - similar yet clinically distinct inflammatory syndromes related to T-cell activation and expansion of multiple cytokines. Differences in tumor biology between MM and DLBCL and how they contribute to differences in cytokine expression is not well understood. Given different CAR T-cell constructs have varying levels of activation and toxicity, cytokine profiles between products and between different disease entities may inform management. In this study, we used multiplex proteomic profiling to evaluate differences in plasma cytokine signatures between two CAR T-cell products and diseases. Methods: Between September 2021 and March 2022, 20 patients received CAR T-cell therapy and consented to the Yale School of Medicine hematologic disease tissue bank (HIC#1401013259). Two longitudinal cohorts were prospectively enrolled: (1) patients who received lisocabtagene maraleucel (liso-cel) for DLBCL refractory after two lines of therapy, and (2) those who received idecabtagene vicleucel (ide-cel) for MM refractory after 4 lines of therapy. For each patient, the first sample was collected prior to lymphodepleting chemotherapy on day -5 with subsequent samples collected on days 0 (prior to CAR T-cell infusion) and 1, 2, 3, and 7 (after CAR T-cell infusion). Plasma samples were processed and frozen within 1 hour of collection. Proteomic profiling was performed at Eve Technologies (Calgary, Alberta, Canada). The Human 71-Plex Discovery Assay measuring 71 total cytokines and chemokines was used to interrogate each sample time point. Statistical analysis was performed in GraphPad Prism (GraphPad Software, San Diego, CA) and R (R Core Team). Levels of individual proteins were compared using Wilcoxon tests. P-values <0.05 were considered statistically significant. Results: Among 13 patients who received liso-cel for DLBCL (including 2 with transformed follicular lymphoma and 3 with double/triple hit pathology), the median age was 66 years (44-82), 7 (54%) were males, 8 (62%) had KPS ≥ 90, 8 (62%) had bulky disease, median lines of therapy were 4 (2-10), and 11 (85%) received systemic bridging therapy. Seven patients (54%) had any grade CRS, with one patient having grade 3 CRS; 2 (15%) had grade 1 and 2 ICANS. Four patients (31%) received an IL-6 inhibitor. At 3 months of follow-up, the objective response rate was 77% (10/13), of whom two patients had a complete response and 60% (6/10) had any grade CRS. Among 7 patients who received ide-cel for MM, with R-ISS score of 1, 2, and 3 in 4 (57%), 1 (14%), and 2 (29%) patients, respectively, the median age was 61 years (54-79), 5 (71%) were males, 4 (57%) had KPS ≥ 90, 3 (43%) had extramedullary disease, median lines of therapy were 7 (4-13), and 5 patients (71%) received systemic bridging therapy. Six patients (86%) had any grade CRS with no patients having grade ≥ 3 CRS; 3 (43%) had grade 1 ICANS. Four patients (57%) received an IL-6 inhibitor. Five patients (63%) received growth factor support on day 7. At 3 months of follow-up, the objective response rate was 86% (6/7) of whom two patients had a complete response and 83% (5/6) had any grade CRS. In a longitudinal analysis, significantly higher levels of IL-3, IL-5, IL-6, IL-10, IL-15, IL-309, and TNFα were noted during CRS (panel 1). In a comparison between CAR constructs, ide-cel was characterized by significantly higher levels of Eotaxin-2, FLT-3L, IL-5, IL-6, IL-15, I-309, MCP-1, and MCP-4 compared to liso-cel (panel 2). Many of these elevated cytokine proteins are implicated as chemoattractants for other leukocyte subtypes including but not limited to neutrophils, monocytes, eosinophils which may contribute to inflammation and may modulate response, toxicity, or relapse. Conclusions: Ide-cel is associated with a distinct cytokine and chemokine signature compared to liso-cel. This study provides pre-clinical evidence for the role of IL-5 inhibitors to treat or prevent CRS following MM-directed CAR T-cell therapy. Further studies with larger cohorts of patients are needed to validate these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Infectious Complications of B-Cell Maturation Antigen (BCMA)-Targeted Therapies for Relapsed/Refractory Multiple Myeloma

Background: Recently, therapeutics targeting B-cell Maturation Antigen (BCMA), including CAR T cells, bispecific antibodies (bsAbs) and antibody-drug conjugates (ADCs), have shown promise in improving outcomes in RRMM patients (pts). However, targeting BCMA can impair natural humoral immunity and increase infection risk. It remains unknown if BCMA-targeted therapies predispose pts to infection at higher frequency or with different characteristics than non-BCMA-targeted therapies in this RRMM population, or if the frequency and characteristics of infections differ amongst the various BCMA-targeted modalities. Methods: We conducted a single-center retrospective study of RRMM pts who started BCMA-targeted therapies (CAR T, bsAb, or ADC) or a selinexor-based treatment between Nov. 2015 and May 2021. We extracted data on patient demographics, MM characteristics, prior lines of therapy, neutrophil and lymphocyte counts, and response to therapy, as well as frequency, type, and severity of infections, quantitative immunoglobulins, and use of intravenous immunoglobulin (IVIG). Pts who had received serial BCMA-targeted therapies, or both a BCMA-targeted therapy and selinexor were excluded from analysis. Results: There were 134 pts included in the analysis: 112 who received a BCMA-targeted treatment (36 CAR T, 29 bsAb, and 47 ADC) and 22 who received selinexor-based treatment. Overall pt characteristics, including age, median lines of therapy, and %triple- and penta-refractory, were similar between the anti-BCMA therapy and selinexor groups, as well as amongst pts receiving the different anti-BCMA modalities. However median duration of therapy differed between groups, longest in the bsAb group and shortest for selinexor (Table 1). Of pts receiving BCMA-targeted treatment, 63 (56%) experienced at least 1 infectious complication (75% of CAR T, 48% of bsAb, and 47% of ADC pts), compared to 6 pts (27%) in the selinexor group. These 69 pts had a total of 146 infections (mean of 2.0, 2.9, 2.1, and 1.0 infections per infected pt in the CAR T, bsAb, ADC, and selinexor groups, respectively) (Table 2). Of the infections in the BCMA-treated pts, 70% were considered low-severity (no treatment or oral treatment alone) and 30% were high-severity (hospitalization, life-threatening, or fatal), with similar frequency of high-severity infections amongst pts getting CAR T, bsAb or ADC. Four of 6 infections (67%) in the selinexor group were high-severity. Most (66%) of the low-severity were upper respiratory tract infections, while most high-severity were lower respiratory tract infections (54%) or bacteremia (22%). Low-severity infections were most commonly viral, while high-severity infections were more likely bacterial. Fungal infections were rare (n=2, both in CAR-T patients). Median time to onset of high-severity infections was 59 days in the CAR T cohort compared to 278 days and 124 days in the bsAb and ADC groups, respectively, and 205 days in the selinexor group. Only 12 of the 146 infections (8%) occurred while pts were neutropenic. Median absolute lymphocyte counts (ALC) were low in all groups pre-treatment; amongst pts still on therapy at 3 months, median ALC had increased in all 3 BCMA-treated groups (Table 1). Regarding hypogammaglobulinemia we focused on pts with non-IgG myeloma to limit confounding effects of the monoclonal IgG protein. Amongst non-IgG pts receiving BCMA-targeted treatments (n=50), 70% had IgG<400 pre-treatment, which increased to 87% by 3 months. For non-IgG selinexor pts (n=9), these numbers were 67% and 71%, respectively. At least 1 dose of IVIG was given in 31% of BCMA-treated pts (22% of CAR T, 59% of bsAb, and 21% of ADC). Conclusions: RRMM pts treated with BCMA-targeted therapies are at high risk of developing an infectious complication, regardless of treatment modality, with many patients having multiple infections, and up to 30% developing high-severity infections. Infection frequency in this study appeared higher for anti-BCMA-treated pts than for selinexor-treated patients, though this finding is confounded by the small numbers and shorter duration of therapy in the selinexor group. Further analyses of the impact of response, ALC, immunoglobulin levels, and IVIG use on infection risk and severity are ongoing. These data demonstrate a need for optimizing strategies to prevent and treat infectious complications in RRMM pts receiving BCMA-targeted therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Daratumumab-Containing Regimens in Outcomes of Subsequent Treatments of Relapsed Multiple Myeloma in Real-World Practice from the Canadian Myeloma Research Group Database

Background: Although daratumumab-containing regimens improve the outcome of relapsed multiple myeloma (MM), the disease remains incurable. We recently published the outcome of daratumumab-based treatment in 583 relapsed myeloma patients in real-world practice (LeBlanc R et al. Br J Haematol 2022). Here we present outcomes of these patients at time of subsequent treatments for relapse immediately after their daratumumab-containing regimen. Methods: We performed a retrospective study using the Canadian Myeloma Research Group Database (CMRG-DB), containing real-world data on outcomes for myeloma patients from Canadian academic centers. From this CMRG-DB, we previously identified 583 relapsed MM patients grouped in 4 daratumumab-containing regimens (DVd: n=143, DRd/p: n=263, DPd/p: n=77 and Dd/p: n=100). Expanding on the initial dataset, the objectives of this study were to benchmark clinical efficacy of subsequent treatment immediately following the daratumumab-containing regimens in terms of responses, progression-free survival (PFS) and overall survival (OS). Results: Of the 583 relapsed MM patients receiving daratumumab-based therapy, after a median follow-up of 21 months (DVd: 16 months, DRd/p: 17 months, DPd/p: 28 months and Dd/p: 32 months), 178 patients are still on their daratumumab-based therapy, 116 patients died before subsequent therapy, 19 patients relapsed but did not initiated subsequent therapy and 2 patients declined subsequent therapy. Subsequent therapy was initiated in 268 patients following daratumumab-containing treatment. These patients were male in 55%, with a median age of 67.8 years (range 36.9-89.7 years) at time of post-daratumumab-containing therapy and had previously received 4 median lines of therapy (range 2-10) at that time. These patients were triple-class exposed in 97% and triple-class refractory in 59% including 89% refractory to lenalidomide; 66% of patients were previously exposed to autologous stem cell transplantation. At the time of subsequent therapy, the median PFS and OS for the entire cohort were 5.2 months (95% CI 4.3-6.5) and 16.4 months (95% CI 13.8-18.9) respectively, as shown in Figure 1. Triple-class refractory patients (n=157) had a trend for a worst outcome with median PFS and OS of 4.7 months (95% CI 3.9-6.3) and 14.6 months (95% CI 11.5-18.9), respectively compared to 5.4 months (95% CI 4.1-8.0) and 17.8 months (95% CI 14.2-29.7) for non-triple-class refractory patients (n=111), with a p-value of 0.18 for PFS and 0.16 for OS. Overall response rate for this entire cohort was 53% with 28% ≥VGPR. Based on regimens used at the time of subsequent therapy, higher ORR were achieved with immunomodulator drugs (IMiDs) and proteasome inhibitors (PIs) or IMiDs or PIs in combination with cyclophosphamide (Cy) compared to IMiDs or PI with steroids alone: ORR IMiD-Cy (n=46) 54%; PI-Cy (n=36) 66% and IMiD-PI (n=24) 63%. From patients treated with anti-CD38 monoclonal antibodies (daratumumab: n=18 and isatuximab: n=1) following daratumumab-containing regimens, ORR was 61% with 11% ≥VGPR; despite the fact that 90% of these patients were daratumumab-refractory. However, the median PFS for all treatment groups were shorter than 8 months, including those patients subsequently participating in a clinical trial as the next line of therapy [best subgroup achieving a median PFS of 7.9 months (95% CI 5.2-11.9)], as shown in Figure 2. Accordingly, the best OS was achieved in this same subgroup of patients participating in clinical trials (n=52) at time of relapse [median OS of 36.5 months (95% CI 21.1-not reached yet)]. Conclusion/summary: Our observations demonstrate that these poor results in real-world practice after daratumumab-based treatment gives rise to a high-risk patient population. We need effective novel therapies for such patients and dedicated prospective trials to better address their needs. Indeed, our results support participation to clinical trials where novel drugs/regimens are made available, as the best outcome is achieved in these patients relapsing following daratumumab-containing regimens. In the absence of this option, standard of care PIs and IMiDs remain the cornerstones of therapy but with limited long term disease control. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Phase I study combining pembrolizumab and aromatase inhibitor in patients with metastatic hormone receptor–positive breast cancer.

1053 Background: Aromatase inhibitor (AI) is standard of care for patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). The current phase I trial was designed to test the safety and efficacy of AI and the immune checkpoint inhibitor pembrolizumab (NCT 02648477). Methods: Key eligibility criteria were HR+ HER2- MBC per ASCO/CAP; RECIST 1.1 measurable disease; adequate organ function; and ECOG 0-1. Eligible patients received 200 mg pembrolizumab IV every 3 weeks plus AI until progression or unacceptable toxicity. Primary objectives were to evaluate the safety and efficacy of this combination. This study employed a 3-at-risk design with a lead-in at the standard dosing of both AI and pembrolizumab with a targeted accrual of 20 patients. Results: A total of 20 patients were accrued between March 2016 and April 2017. Median age was 62 (range 34-79), with 75% white, 15% Asian and 10% unknown. Median lines of therapy were 3 (0, 9). All but one patient received aromatase inhibitor and/or fulvestrant prior to enrollment. The combination was well tolerated, and the most common adverse events were grade 2 fatigue (35%), rash (15%), and hot flashes (10%). Grade 3 adverse events were elevated AST/ALT (5%), rash (5%), and lymphopenia (5%). Responses were 10% partial response and 15% stable disease, resulting in a clinical benefit rate (CBR) of 20% at 6 months. Median follow-up time was 40.1 months (range 31.3 – 46.8 months). Median progression free survival was 1.8 months (95% CI 1.6, 2.6) and median overall survival was 17.2 months (95% CI 9.4, NA). 14 tumor specimens had programmed death ligand 1–positive (PD-L1) by 22C3 testing, including 3 PD-L1-positive and 11 PD-L1 negative. No association between PD-L1 and response was found. Conclusions: The combination of pembrolizumab and AI is well tolerated in patients with HR+ HER2- MBC who were not pre-selected for PD-L1. There was minimal overall clinical activity observed beyond what was to be expected with AI alone in this group of patients. Clinical trial information: NCT 02648477.

Physical Function, Psychosocial Status, and Symptom Burden Among Adults with Plasma Cell Disorders and Associations with Quality of Life.

BackgroundThe plasma cell disorders (PCDs), multiple myeloma (MM), and light-chain amyloidosis (AL) are disproportionately diseases of older adults, whose care may be complicated by frailty associated with advancing age. We sought to evaluate the prevalence of functional deficits and symptoms in a cohort of persons with PCDs and associations of demographic, disease-related, functional, and psychosocial measures with quality of life (QoL).Patients and MethodsAdults with PCDs were recruited into an observational registry in 2018-2020. Patients completed a functional assessment and European Organization for Research and Treatment of Cancer QoL questionnaire (QLQ-C30). Associations of covariates of interest with QoL were evaluated via univariate linear regression.ResultsAmong 121 adults, the mean age was 68.6. Diagnoses were 74% MM, 14% AL, 7% both MM and AL, and 5% other PCDs. The median time from diagnosis was 34.9 months. Median lines of therapy were 2, with 11% having received ≥4th-line therapy.Patients with functional deficits had lower mean QoL scores: dependence in IADLs (66.3 vs. 79.9, P = .001) and recent falls (56.7 vs. 76.8, P = .001). Patients ≤6 months from diagnosis had lower QoL (66.7) than those ≥2 years from diagnosis (77.3, P = .03). However, patients on later lines of therapy (≥4th-line) had lower QoL (62.2) than those on 1st-line treatment (76.0, P = .04).ConclusionsPatients with physical impairments and more advanced PCDs had lower QoL than those without deficits or earlier in their disease course. Early identification of physical impairments may facilitate interventions that mitigate these deficits and thereby improve QoL for patients with PCDs.

Abstract PD8-09: Predicted financial impact of continued HER2-directed therapy in metastatic breast cancer: What is the financial toxicity in a public payer healthcare system?

Abstract Background Continued HER2 suppression in metastatic breast cancer (MBC) has been demonstrated to improve progression free survival (PFS) and overall survival (OS) in many randomized studies to date. Current funding policy in British Columbia (BC) restricts to two lines of HER2 directed therapy (HER2Rx) in MBC. With the development of novel HER2Rx agents, accessing continued HER2 suppression in the MBC has become complex. The financial implications of adapting future funding policies to reflect increasing lines of proven HER2Rx is unknown. Purpose The purpose of this study is to assess the proportion of patients with HER2 positive MBC eligible to receive systemic therapy beyond 2 lines of HER2Rx. We also wished to assess the proportion of eligible patients who accessed continued HER2Rx despite lack of public funding, and how their treatment beyond second line was funded. Methods The BC outcomes unit collects clinical and outcome information on 85% of all patients diagnosed with in the province of BC. In addition, all anti-neoplastic therapy delivered in the province is recorded in the BC Cancer pharmacy database. These two databases with queried and cross referenced to identify patients who received any HER2Rx for MBC dispensed by BC Cancer between 2013 and 2018, in the era where trastuzumab plus pertuzumab and TDM-1 were standard options and publically available. The number of lines of therapy received, specific treatments, and fitness to continue therapy beyond two lines were analyzed through targeted chart review. PFS and OS data were also analyzed. Expected financial implications were calculated based on current cost of most commonly used therapies in the third line. Results We identified 230 patients who met inclusion criteria with detailed information about treatment at the time of analysis. 51% (117) of these patients were eligible to continue therapy beyond second line. Of these, 86 (37% of the whole cohort) did access continued HER2-directed therapy, while 26 (11% of the whole cohort) were eligible but unable to access continued HER2Rx. The remaining 49% of were not eligible for consideration of further HER2Rx due to either stable disease on current treatment or deterioration precluding further treatment. The median lines of therapy in the entire study population was 3. Minimum lines of therapy was 1, maximum number of lines of therapy delivered was 12. Median number of cycles of therapy received beyond second line for those eligible to continue treatment was 22 cycles. Median OS for those who continued HER2Rx was 58.6 months compared to 38.0 months for those who were eligible but did not continue therapy, but this was not statistically significant (p = 0.13). The vast majority of these patients are receiving continued HER2Rx through either exceptional access or clinical trial, and very rarely through private pay or insurance. Conservative estimated cost per cycle of HER2Rx was based on currently available biosimilars to Trastuzumab. If these trends in survival continue we would expect an additional cost of $44000 per patient over current costs. Conclusion 51% of patients with HER2 positive MBC are eligible to receive more than two lines of HER2 directed systemic therapy. Of these eligible patients, the majority of patients (77%) are accessing treatment despite prohibitive funding policies, based on clinical trial or compassionate access programs. As funding policies adapt to the evolving treatment landscape for patients with HER2 positive MBC, we can expect a significant increase in cost per patient in this setting with conservative estimates of $44000 per patient above current costs. As the cost of novel therapies are likely to be higher than currently available biosimilars, there will be significant implications for both private payer and public payer healthcare systems. Citation Format: Emily B Jackson, Lauren Corke, Hyejee Ohm, Christine Simmons. Predicted financial impact of continued HER2-directed therapy in metastatic breast cancer: What is the financial toxicity in a public payer healthcare system? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD8-09.

Phase 1/2 Trial of IL7/IL15-Expanded Bispecific LV20.19 CAR T-Cells for Relapsed, Refractory B-Cell Non-Hodgkin Lymphoma

Phase 1/2 Trial of IL7/IL15-Expanded Bispecific LV20.19 CAR T-Cells for Relapsed, Refractory B-Cell Non-Hodgkin Lymphoma

Gda-201, a Novel Metabolically Enhanced Allogeneic Natural Killer (NK) Cell Product Yields High Remission Rates in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma (NHL): 2-Year Survival and Correlation with Cytokine IL7

Gda-201, a Novel Metabolically Enhanced Allogeneic Natural Killer (NK) Cell Product Yields High Remission Rates in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma (NHL): 2-Year Survival and Correlation with Cytokine IL7

An Observational Study on Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens Outside Clinical Trials in Italy (GIMEMA CLL1920)

An Observational Study on Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens Outside Clinical Trials in Italy (GIMEMA CLL1920)

30-Day Mortality Following Systemic Anti-Cancer Treatment (SACT) Review in Driving Quality of Care in Hematologic Malignancies in a Tertiary Care Hospital

IntroductionThere is growing evidence to support SACT 30-day mortality rate as a key metric for assessing quality of cancer care and a key indicator of avoidable harm to patients from SACT due therapy-related or poor patient selection factors. This has been established for solid organ malignancy. However, data in patients with hematologic malignancy is limited. At the Gloucestershire Hospitals NHS Foundation Trust, a large district general hospital providing specialist care to over 600,000 people, we collated data from our in-house SACT dataset to assess factors that impact the 30-day SACT mortality and establish a benchmark for multidisciplinary, educational mortality meeting discussions on mortality in patients receiving SACT. We aimed to review cases characterizing patients, causes of death and the role of SACT in deaths.MethodsThis retrospective study included all patients aged 18 years or older with a hematologic malignancy who received SACT between Jan 1, 2016, and Mar 31, 2021, irrespective of the number of previous treatment cycles or regimens and irrespective of their response within the disease trajectory. SACT was defined as any cytotoxic chemotherapy, immunotherapies such as monoclonal antibodies, and targeted biological treatments. We calculated 30-day mortality after the most recent cycle of SACT for these patients. We analyzed whether patient, tumor type, and therapy-related factors were associated with the risk of 30-day mortality.ResultsA total of 1903 patients with hematologic malignancy received SACT. The 30-day mortality rate for our center was 3.89% for patients receiving SACT and 4.9% of all-cause mortality. In the 30-day mortality cohort the median patient age at death was 71 years (interquartile range (IQR) 52-86); ratio of men to women, 1.18. 30-day mortality increased with age for patients treated with palliative intent or intent to remission (OR 4.9, 95% CI .985-26.255; p=0.0171). Median duration of 30-mortality post SACT was 17 days (IQR 8-22). The commonest malignancy was plasma cell dyscrasias (54%) and 68% receiving treatments with intent to remission. ECOG performance status was 0-2 at final SACT cycle in 65%, 3 in 27% and 4 in 8%. 47% of patients were receiving their first cycle (median number of cycles received 2; IQR 1-3) and 43% receiving first line therapy (median lines of therapy 2; IQR 1-3). Therapy naïve patients had significantly higher 30-day mortality than those who received previous SACT (OR 3.435, 95% CI 2.06-5.66; p<0·0001). 42% of deaths occurred in hospital and 54% were attributed to primary refractory and/or aggressive disease. Other causes of death included infection (19% neutropenic, 15% non-neutropenic) including COVID-19 (3%), major bleed (5%), thromboembolism (1%) and cardiac event (1%).ConclusionsSACT data provides “real world” assessment of treatment patterns and outcomes in routine malignant hematology practice. It highlights the importance of systematic data collection and analyses to better inform factors associated with higher risk of 30-day mortality in patients with hematologic malignancy, which ultimately promotes review of clinical decision making and offers an opportunity for service improvements. Our findings shed light into some of the factors that affect the risk of early mortality of patients with hematologic malignancy and provides a way to measure if the health service is improving. The insights into risk factors for 30-day mortality will aid in better understanding for treating clinicians and their patients on predictors of potential harms and benefits of SACT thereby carefully balancing patients' personalized expectations with representative outcomes and treatment risks and should be the focus of discussions about SACT, particularly in pretreated or older patient groups. Neutropenic sepsis remains a significant cause of SACT related mortality warranting further improvements in care. Prospective case discussions together with this retrospective review have generated service improvements at our center including standardizing chemotherapy helpline pathways, systematizing SACT mandatory data recording on e-prescribing system and mandatory response assessments as part of SACT protocols' review. Future research work to examine outcomes based on subtypes of hematologic malignancy and on larger datasets is critical for improving our understanding at delivering the right drugs to the right patients. DisclosuresNo relevant conflicts of interest to declare.

Ethnic Disparities in Waldenström's Macroglobulinaemia in the United Kingdom - Analysis from the Wmuk Rory Morrison Registry

Introduction: Waldenström's Macroglobulinaemia (WM) is a rare indolent B-cell lymphoma characterised by lymphoplasmacytic infiltrate with an IgM paraproteinaemia. Approximately 400 patients (pts) are diagnosed annually in the United Kingdom (UK). National and regional registries provide important insights on the epidemiology and clinical features of this distinct uncommon disorder. Previous authors from the United States have reported significant differences in age at diagnosis and overall survival (OS) in WM between ethnic groups from Surveillance, Epidemiology and End Results data [1]. We aimed to determine baseline demographics, symptoms and survival outcomes across different ethnic groups in the UK.Methods: We retrospectively reviewed data from the WMUK Rory Morrison Registry, collating descriptive data of WM as well as non-IgM Lymphoplasmacytic lymphoma (LPL) cases from 20 centres across the UK, diagnosed between June 1978 and May 2021. Research ethics approval was obtained.Results: 732 pts with documented ethnicity were included here. Ethnicity was categorised in accordance with the UK National Census. Those other than the White cohort (662/732; 90%) were collectively termed ‘Ethnic Minorities’ (EM) (70/732; 9%): 39/70 (56%) Asian (13 Indian, 6 Chinese, 4 Pakistani, 16 other); 19/70 (27%) Mixed (1 White & Black African, 1 White & Asian, 1 Arab, 16 other); 12/70 (17%) Black (6 Caribbean, 3 African, 3 other).Baseline characteristics are displayed in table 1. EM presented at a significantly younger age compared to White cohort (60 vs 64 years, p=0.01) and had a significantly lower paraprotein at diagnosis (11 vs 18g/L, p=0.05). MYD88 L265P mutation tested in 250 pts (34%): positive in the majority 218/250 (87%) and notably less common in EM (p=0.09), most significantly in the Asian cohort compared to White (67% v 88%, p=0.01). The EM cohort had a smaller proportion of WM diagnoses compared to White cohort (77% vs 93%, p=0.02) with the Asian cohort accounting for the highest proportion of non-IgM LPL (15% vs 4%, p=0.002). Bone marrow trephine infiltration at diagnosis was lower in the EM cohort compared to the White cohort, although not statistically significant (25% vs 37%, respectively; p=0.10). IPSSWM scores were similar throughout.Approximately half of both the White & EM cohorts were asymptomatic at diagnosis. The most common presenting symptoms in EM were anaemia-related (10/34; 29%), B symptoms (6/34; 18%) and fatigue (4/34; 12%). 6/18 (33%) of Asians presented with cryoglobulinaemia, amyloid, nephropathy or acquired von Willebrand's Disease.Of EM, 51/70 (73%) had treatment, 35/51 (69%) within the first year from diagnosis with time to treatment 2 months (range 0-364). Time to next therapy was 14 months. Median lines of therapy were 2 (range 1-8). The most common indication for first line therapy was lymphoma-related (16/39; 41%) followed by paraprotein-related (peripheral neuropathy, hyperviscosity and autoimmune) (13/39; 33%). First line therapies included Bendamustine-Rituximab (BR; 8/49; 16%), Dexamethasone Rituximab Cyclophosphamide (DRC; 7/49; 14%) and R-CHOP (5/49; 10%) with smaller proportions receiving Rituximab monotherapy, Cladribine + Rituximab or Fludarabine + Cyclophosphamide + Rituximab (FCR) (3/49 (6.1% each). Two of 41 (5%) of EM had first treatment as a part of a clinical trial, compared to 16/156 (10%) of the White cohort (p=0.28). Response to first line therapy was similar between the White & EM cohorts (Table 1).For EM, at a median follow up of 7 years, 17 died (1/17; 6% disease related). Median OS was not reached (Figure 1). Estimated 5-year and 10- year OS was 91% (95% CI 96-80%) and 75% (95% CI 85-60%), respectively.Conclusions: This first report on ethnic disparities in WM and non-IgM LPL in the UK identified key differences in presentation of disease. Ethnic minorities present at a younger age, with a lower paraprotein. The Asian cohort had a greater proportion of non-IgM LPL cases and fewer MYD88 mutated cases. A small proportion of Ethnic Minorities have treatment on a clinical trial which may warrant further attention. Further analysis including associations with socioeconomic status, deprivation indices and comorbidities are ongoing.•Ailawadhi, Sikander et al. “Outcome disparities among ethnic subgroups of Waldenström's macroglobulinemia: a population-based study.” Oncology vol. 86,5-6 (2014): 253-62. doi:10.1159/000360992 DisclosuresMcCarthy: Janssen: Honoraria; Astra zenica pharmaceuticals: Honoraria; Amgen: Honoraria. Pratt: Amgen: Consultancy; Binding Site: Consultancy; BMS/Celgene: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Takeda: Consultancy. El-Sharkawi: AbbVie: Honoraria, Other: Travel Support, Ad boards; AstraZeneca: Honoraria, Other: Ad boards; Janssen: Honoraria, Other: Ad boards; Roche: Honoraria; Takeda: Honoraria; Novartis: Other: Travel Support; ASTEX: Other: Ad boards; Beigene: Other: Ad boards; Kyowa Kirin: Other: Ad boards. Linton: Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptitude Health: Honoraria; Hartley Taylor: Honoraria; Celgene: Research Funding; BeiGene: Research Funding; University of Manchester: Current Employment. Gatto: Roche: Consultancy. D'Sa: Janssen Cilag: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding; Sanofi: Honoraria.

Safety and Efficacy of B-Cell Maturation Antigen (BCMA)-Specific Chimeric Antigen Receptor T Cells (CART-BCMA) with Cyclophosphamide Conditioning for Refractory Multiple Myeloma (MM)

Abstract Background: CART-BCMA is an autologous T cell product engineered by lentiviral transduction to express a fully human BCMA-specific CAR with CD3ζ and 4-1BB signaling domains and expanded ex vivo using anti-CD3/anti-CD28 beads. We reported early safety and clinical activity of CART-BCMA without lymphodepleting chemotherapy in highly refractory MM patients (pts) (Cohen et al, ASH 2016, #1147). Here we report extended results from this initial cohort, as well as initial safety and efficacy in additional cohorts at 2 dose levels in conjunction with cyclophosphamide (Cy). Methods: Three cohorts are being enrolled: 1) 1-5 x 108 CART cells alone; 2) Cy 1.5 g/m2 + 1-5 x 107 CART cells; and 3) Cy 1.5 g/m2 + 1-5 x 108 CART cells. CART-BCMA cells are given as split-dose infusions (10% on day 0, 30% on day 1, and 60% on day 2), with Cy given on day -3. Pts need serum creatinine (Cr) Disclosures Cohen: Bristol Meyers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Celgene: Consultancy; Janssen: Consultancy. Lacey: Novartis: Research Funding; Genentech: Honoraria. Lancaster: Amgen: Consultancy; Janssen: Consultancy. Vogl: Karyopharm: Consultancy; Amgen: Consultancy; Teva: Consultancy; Calithera: Research Funding; GSK: Research Funding; Celgene: Consultancy; Takeda: Consultancy, Research Funding; Constellation: Research Funding. Weiss: Prothena: Research Funding; Alnylam: Honoraria; Janssen: Honoraria; Janssen: Research Funding; Prothena: Honoraria. Chen: Novartis: Research Funding. Young: Novartis: Research Funding. Richardson: Novartis: Employment. Isaacs: Novartis Pharmaceuticals: Employment. Melenhorst: Novartis: Research Funding. Levine: GE Healthcare: Consultancy; Tmunity Therapeutics: Equity Ownership, Research Funding; Brammer Bio: Consultancy; Novartis Pharmaceuticals Corporation: Patents & Royalties, Research Funding. June: Novartis: Patents & Royalties, Research Funding; Immune Design: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Tmunity Therapeutics: Equity Ownership, Research Funding; WIRB/Copernicus Group: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celldex: Honoraria, Membership on an entity's Board of Directors or advisory committees. Milone: Novartis: Patents & Royalties.

Influence of treatment access on survival of metastatic renal cell carcinoma in brazilian cancer center.

ABSTRACTBackground:Tyrosine kinase inhibitors (TKI) and immunotherapy improved survival in metastatic renal cell carcinoma (mRCC). Disparities in treatment access are present in healthcare systems globally. The aim of this study was to analyze survival outcomes of mRCC patients treated with first-line TKIs in the public (PHS) and private (PrS) health system in a Brazilian Cancer Center.Materials and Methods:Records from all mRCC patients treated with first-line TKIs from 2007-2018 were reviewed retrospectively. Categorial variables were compared by Fisher's exact test. Survival was estimated by Kaplan-Maier method and survival curves were compared using the log-rank test. Prognostic factors were adjusted by Cox regression model.Results:Of the 171 eligible patients, 37 (21.6%) were PHS patients and 134 (78.4%) were PrS patients. There were no difference in age, gender, or sites of metastasis. PHS patients had worse performance status (ECOG ≥2, 35.1% vs. 13.5%, p=0.007), poorer risk score (IMDC poor risk, 32.4% vs. 16.4%, p=0.09), and less nephrectomies (73% vs. 92.5%, p=0.003) than PrS patients. Median lines of therapy was one for PHS versus two for PrS patients (p=0.03). Median overall survival (OS) was 16.5 versus 26.5 months (p=0.002) and progression-free survival (PFS), 8.4 versus 11 months (p=0.01) for PHS and PrS patients, respectively. After adjusting for known prognostic factors on multivariate analysis, PHS patients still had a higher risk of death (HR: 1.61, 95% CI: 1.01-2.56, p=0.047).Conclusion:Patients with mRCC treated via the PHS had worse overall survival, possibly due to poorer prognosis at presentation and less drug access.