scholarly journals Enhancing Diversity in Oncology Clinical Trials: Findings of a Case Study in Improving Black Patient Representation in a Multiple Myeloma Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3008-3008
Author(s):  
Sudip Bhandari ◽  
Charles Lagor ◽  
Judith Mueller ◽  
Warren Whyte ◽  
Samuel Heilbroner
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Medical Record ◽  
Electronic Medical Record ◽  
Health Disparity ◽  
Black Patient ◽  
The United States ◽  
Black Patients ◽  
Car T

Abstract Background: Black patients are underrepresented in multiple myeloma (MM) clinical trials. Despite the promise of Real-World Data (RWD), little research exists on RWD's usage to address this health disparity. In collaboration with a large pharmaceutical partner, we used RWD from commercial datasets (ConcertAI's Electronic Medical Record and claims datasets) aimed at identifying sites with a large Black patient population. We recommended including these sites in a recent clinical trial of Chimeric Antigen Receptor T cell (CAR-T) therapy for MM patients. Methods: We used the following criteria to identify promising sites: (1) high Black patient density, (2) access to a CAR-T accredited parent organization within 100 miles, (3) a hematologist/oncologist who treats MM patients, and (4) a history of treating MM patients with a Proteasome Inhibitor (PI) and Lenalidomide (Len) in the first line of therapy. For (1), sites were ranked using the lower 95% confidence interval for the percent of Black MM patients at the site. For (4), only sites with at least five MM patients who received PI and Len were included. Our data sources were: ConcertAI's Electronic Medical Record (EMR) and claims datasets to link each patient to a site, and Google maps API to identify the CAR-T center nearest each oncology site. The patients in our data sets were not identifiable, and our research was conducted in compliance with the Health Insurance Portability and Accountability Act. After having identified and filtered promising sites, we curated individual candidates in the order of Black patient density. The purpose of curation was to validate a final list of sites. Results: We identified 17 promising clinical trial sites affiliated with 16 healthcare systems in the mid-west, mid-Atlantic, southeastern, and southwestern regions of the United States (table 1). Our RWD captured an average of 141 MM patients (range: 6-791) who were treated at the 17 sites from 2015-2020. Thirty-nine percent of the patients were Black (range: 13-67%). This percentage was three times the recruitment rate of black patients in MM trials in the US (13%). On average, the sites were 44 miles driving distance (range: 0.8-96 miles) from the closest CAR-T center, had eight hematology/medical oncology specialists on staff (range: 1-17), and had previous interventional trial experience (13 sites had experience with MM trials). All of the identified sites were community-based sites, and none of the sites were previously identified by our pharmaceutical partner. Conclusions: We demonstrated that RWD can be leveraged to identify clinical trial sites with a high potential for Black patient recruitment, thereby addressing a known health disparity problem within multiple myeloma (MM) clinical trials. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Safety and Efficacy of Anti-Bcma CAR-T Cells for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Literature

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Israr Khan ◽  
Abdul Rafae ◽  
Anum Javaid ◽  
Zahoor Ahmed ◽  
Haifza Abeera Qadeer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cells ◽  
Partial Response ◽  
Residual Disease ◽  
Safety And Efficacy ◽  
Refractory Multiple Myeloma ◽  
Car T Cells ◽  
Car T

Background: Multiple myeloma (MM) is a plasma cell disorder and demonstrates overexpression of B cell maturation antigen (BCMA). Our objective is to evaluate the safety and efficacy of chimeric antigen receptor T cells (CAR-T) against BCMA in patients with relapsed/refractory multiple myeloma (RRMM). Methods: We conducted a systematic literature search using PubMed, Cochrane, Clinicaltrials.gov, and Embase databases. We also searched for data from society meetings. A total of 935 articles were identified, and 610 were screened for relevance. Results: Data from thirty-one original studies with a total of 871 patients (pts) were included based on defined eligibility criteria, see Table 1. Hu et al. reported an overall response rate (ORR) of 100% in 33 pts treated with BCMA CAR-T cells including 21 complete response (CR), 7 very good partial response (VGPR), 4 partial response (PR). Moreover, 32 pts achieved minimal residual disease (MRD) negative status. Chen et al. reported ORR of 88%, 14% CR, 6% VGPR, and 82% MRD negative status with BCMA CAR-T therapy in 17 RRMM pts. In another clinical trial by Han et al. BCMA CAR-T therapy demonstrated an ORR of 100% among 7 evaluable pts with 43% pts having ≥ CR and 14% VGPR. An ORR of 100% with 64% stringent CR (sCR) and 36% VGPR was reported with novel anti-BCMA CART cells (CT103A). Similarly, Li et al. reported ORR of 87.5%, sCR of 50%, VGPR 12.5%, and PR 25% in 16 pts. BCMA targeting agent, JNJ-4528, showed ORR of 91%, including 4sCR, 2CR, 10MRD, and 7VGPR. CAR-T- bb2121 demonstrated ORR of 85%, sCR 36%, CR 9%, VGPR 57%, and MRD negativity of 100% (among 16 responsive pts). GSK2857916, a BCMA targeting CAR-T cells yielded ORR of 60% in both clinical trials. Three studies utilizing bispecific CART cells targeting both BCMA & CD38 (LCARB38M) reported by Zhao et al., Wang et al., and Fan et al. showed ORR of 88%, 88%, & 100% respectively. Topp et al. reported ORR of 31% along with 5 ≥CR and 5 MRD negative status in 42 pts treated with Bi T-cells Engager BiTE® Ab BCMA targeting antigen (AMG420). One clinical trial presented AUTO2 CART cells therapy against BCMA with an ORR of 43%, VGPR of 14%, and PR of 28%. CT053CAR-BCMA showed 14sCR and 5CR with a collective ORR of 87.5% and MRD negative status of 85% in 24 and 20 evaluable pts, respectively. Likewise, Mikkilineni et al. reported an ORR of 83%, sCR of 16.7%, and VGPR & PR of 25% and 41% in 12 pts treated with FHVH-BCMA T cells. Similar results are also reported in other clinical trials of BCMA targeting CART therapy (Table 1). The most common adverse effects exhibited were grade 1-3 hematologic (cytopenia) and cytokine release syndrome (CRS) (mostly reversible with tocilizumab). Conclusion: Initial data from ongoing clinical trials using BCMA targeting CAR-T therapy have yielded promising results both in terms of improved outcome and tolerable toxicity profiles. Although two phase 3 trails are ongoing, additional data is warranted to further ensure the safety and efficacy of anti-BCMA CAR-T cells therapy in pts with RRMM for future use. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Clinical trial eligibility determination using an oncology electronic medical record system interfaced to a caBIG-certified trial database

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6626-6626
Author(s):  
J. W. Goldwein ◽  
M. Van Der Pas ◽  
L. Tis ◽  
R. Nickens ◽  
R. Comis
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Medical Record ◽  
Electronic Medical Record ◽  
Performance Status ◽  
Stage Iv ◽  
Clinical Trial Registration ◽  
Record System ◽  
Eligibility Determination ◽  
Stage Iv Breast Cancer

6626 Background: One reason for the low numbers of patients entered on cancer clinical trials is the difficulty and inconvenience encountered in determining whether patients are eligible. The introduction of electronic medical record (EMR) systems in cancer facilities provides a means by which clinical parameters may be electronically collected and compared against clinical trial eligibility criteria, with the potential to facilitate eligibility determination. We hereby describe a widely utilized EMR system interfaced to a caBIG-certified searchable clinical trials database which facilitates eligibility determination. Materials and Methods: MOSAIQ is a widely utilized oncology- specific EMR system that is operational in radiation and medical oncology facilities world-wide. During the routine course of patient care, clinical trial eligibility parameters such as diagnosis, stage, age, and performance status are entered into defined data fields within the EMR. Trialcheck is an independently maintained caBIG bronze level certified database that lists thousands of clinical trials from Cooperative Groups, NCI/PDQ, the pharmaceutical industry and trials being conducted exclusively at particular oncology facilities. TrialCheck registrants can screen trials for patient eligibility as well as filter and track the status of trials that have been activated at their facility. In addition, a real-time, secure Internet interface between MOSAIQ and TrialCheck extracts eligibility parameters from a patient record, sends that information to TrialCheck, and returns a listing of matched clinical trials. Results: In a test screen of 4 MOSAIQ EMR patients against 257 TrialCheck clinical trials, the system matched a patient with Stage IV breast cancer to 7 available trials in less 2 seconds, a patient with Stage IIIB colon cancer to 3 trials in 5 seconds, a Stage IV prostate cancer to 5 trials in 4.4 seconds, and a patient with stage II esophageal cancer to 2 trials in 3.7 seconds. Conclusion: This product demonstrates a novel and innovative solution to one of the problems inherent in the clinical trial registration process in an efficient, reliable and secure manner. No significant financial relationships to disclose.

scholarly journals An Institutional Retrospective Study on Recognizing the Delay in Multiple Myeloma Diagnosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3430-3430
Author(s):  
Nima Ghalehsari ◽  
Pragnan Kancharla ◽  
Neil S Nimkar ◽  
Anita Mazloom ◽  
Farah Ashraf ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Medical Record ◽  
Electronic Medical Record ◽  
Total Protein ◽  
The United States ◽  
Newly Diagnosed ◽  
Average Delay ◽  
Delay In Diagnosis ◽  
Mean Delay

Background Multiple myeloma (MM) is the abnormal proliferation of plasma cells in the bone marrow often resulting in debilitating symptoms ranging from ostealgia to pathological fractures from bone destruction. According to American Cancer Society, MM accounts for 1-2% of cancers and approximately 17% of hematological malignancies in the United States each year (1). Fifty percent of patients with symptomatic MM have three or more primary care visits before they are referred to a specialist, which is greater than any other cancer (5). It has been shown that a delay in diagnosing multiple myeloma negatively impacts the clinical course of the disease and hence the outcome in patients (2). Patients with longer diagnostic intervals also experience shorter disease free survival and more complications from treatment (4). Herein, a retrospective analysis was performed to determine the average delay in diagnosis of MM. Methods This is a retrospective electronic chart review of all indexed newly diagnosed MM cases between 1/1/2014 through 12/31/2018 at New York-Presbyterian Brooklyn Methodist Hospital (NYP BHM). NYP BMH is a Weill Cornell Medical College-affiliated hospital in Brooklyn, NY whose patient population includes those with private insurance, uninsured and Medicare/Medicaid. Data abstraction from the electronic medical record (EMR) was uniform and involved baseline characteristics such as age, gender and race. International Classification of Diseases (ICD)-10-CM code (C90.00) was used for extraction of data which identified 492 patients. After excluding patients with MGUS or a prior diagnosis of multiple myeloma, 104 patients were included in the final study. We calculated the number of days between the date of first abnormal laboratory value seen on bloodwork for a myeloma related sign (at least 90 days prior to diagnosis) to the date of bone marrow biopsy that confirmed the diagnosis. The inclusion criteria were anemia defined as hemoglobin <12gm/dl, Hypercalcemia defined by corrected calcium >10, kidney dysfunction with a creatinine >1.5 and total protein >8. Results Of the 104 patients with newly diagnosed MM, 69 patients were diagnosed within 90 days of the first abnormal lab value recorded in our electronic medical record (EMR). Thirty-five patients (34%) had a delay in diagnosis at least 90 days with a mean delay of 38 months. Isolated anemia was the most common abnormal lab finding with 29/104 (28%) having documented anemia at least 90 days prior to diagnosis of myeloma. The mean delay in diagnosis for patients with anemia was 41 months. There were four patients with anemia and elevated creatinine with an average delay of 23 months. Five patients had anemia and elevated calcium with an average delay of 21 months. Nine patients had anemia and elevated total protein with an average delay of 38 months. Conclusion: In the current era where we have effective therapies for MM it is now more important than ever to avoid a delay in diagnosis. We demonstrate that 34% of patients receiving care at an Urban Teaching Hospital had at least a 90 day delay in their diagnosis of MM. Our cohort consisted of 64% African Americans, suggesting that minorities are more commonly affected by this. There is a need for more awareness amongst clinicians to consider the diagnosis of MM in the workup of anemia. References: 1. Kariyawasan, C. C., D. A. Hughes, M. M. Jayatillake, and A. B. Mehta. 2007. "Multiple Myeloma: Causes and Consequences of Delay in Diagnosis." QJM: Monthly Journal of the Association of Physicians 100 (10): 635-40. 2. Siegel, Rebecca L., Kimberly D. Miller, and Ahmedin Jemal. 2019. "Cancer Statistics, 2019." CA: A Cancer Journal for Clinicians. https://doi.org/10.3322/caac.21551. 3. Vélez R, Turesson I, Landgren O, Kristinsson SY, Cuzick J. Incidence of multiple myeloma in Great Britain, Sweden, and Malmö, Sweden: the impact of differences in case ascertainment on observed incidence trends. BMJ Open. 2016;6:e009584. 4. Kariyawasan CC, Hughes DA, Jayatillake MM, et al. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007;100:635-40. 10.1093/qjmed/hcm077 5. Lyratzopoulos G, Neal RD, Barbiere JM, et al. Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England. Lancet Oncol 2012;13:353-65. 10.1016/S1470-2045(12)70041-4 Disclosures No relevant conflicts of interest to declare.

The Use of Digital Clinical Trial Methods in the Evaluation of Digital Therapeutics: A Scoping Review (Preprint)

2019 ◽  
Author(s):  
Allison Hirsch ◽  
Mahip Grewal ◽  
Anthony James Martorell ◽  
Brian Michael Iacoviello
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Scoping Review ◽  
Digital Technologies ◽  
Good Clinical Practice ◽  
The United States ◽  
Clinical Trial Research ◽  
Digital Methods ◽  
Clinical Trial Methods

BACKGROUND Digital Therapeutics (DTx) provide evidence based therapeutic health interventions that have been clinically validated to deliver therapeutic outcomes, such that the software is the treatment. Digital methodologies are increasingly adopted to conduct clinical trials due to advantages they provide including increases in efficiency and decreases in trial costs. Digital therapeutics are digital by design and can leverage the potential of digital and remote clinical trial methods. OBJECTIVE The principal purpose of this scoping review is to review the literature to determine whether digital technologies are being used in DTx clinical research, which type are being used and whether publications are noting any advantages to their use. As DTx development is an emerging field there are likely gaps in the knowledge base regarding DTx and clinical trials, and the purpose of this review is to illuminate those gaps. A secondary purpose is to consider questions which emerged during the review process including whether fully remote digital clinical research is appropriate for all health conditions and whether digital clinical trial methods are inline with the principles of Good Clinical Practice. METHODS 1,326 records were identified by searching research databases and 1,227 reviewed at the full-article level in order to determine if they were appropriate for inclusion. Confirmation of clinical trial status, use of digital clinical research methods and digital therapeutic status as well as inclusion and exclusion criteria were applied in order to determine relevant articles. Digital methods employed in DTx research were extracted from each article and these data were synthesized in order to determine which digital methods are currently used in clinical trial research. RESULTS After applying our criteria for scoping review inclusion, 11 articles were identified. All articles used at least one form of digital clinical research methodology enabling an element of remote research. The most commonly used digital methods are those related to recruitment, enrollment and the assessment of outcomes. A small number of articles reported using other methods such as online compensation (n = 3), or digital reminders for participants (n = 5). The majority of digital therapeutics clinical research using digital methods is conducted in the United States and increasing number of articles using digital methods are published each year. CONCLUSIONS Digital methods are used in clinical trial research evaluating DTx, though not frequently as evidenced by the low proportion of articles included in this review. Fully remote clinical trial research is not yet the standard, more frequently authors are using partially remote methods. Additionally, there is tremendous variability in the level of detail describing digital methods within the literature. As digital technologies continue to advance and the clinical research DTx literature matures, digital methods which facilitate remote research may be used more frequently.

A Framework for Systematic Assessment of Clinical Trial Population Representativeness Using Electronic Health Records Data

2021 ◽  
Vol 12 (04) ◽  
pp. 816-825
Author(s):  
Yingcheng Sun ◽  
Alex Butler ◽  
Ibrahim Diallo ◽  
Jae Hyun Kim ◽  
Casey Ta ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Electronic Health Records ◽  
The United States ◽  
Design Stage ◽  
Common Data Model ◽  
Free Text ◽  
Eligibility Criteria ◽  
Health Records ◽  
Electronic Health

Abstract Background Clinical trials are the gold standard for generating robust medical evidence, but clinical trial results often raise generalizability concerns, which can be attributed to the lack of population representativeness. The electronic health records (EHRs) data are useful for estimating the population representativeness of clinical trial study population. Objectives This research aims to estimate the population representativeness of clinical trials systematically using EHR data during the early design stage. Methods We present an end-to-end analytical framework for transforming free-text clinical trial eligibility criteria into executable database queries conformant with the Observational Medical Outcomes Partnership Common Data Model and for systematically quantifying the population representativeness for each clinical trial. Results We calculated the population representativeness of 782 novel coronavirus disease 2019 (COVID-19) trials and 3,827 type 2 diabetes mellitus (T2DM) trials in the United States respectively using this framework. With the use of overly restrictive eligibility criteria, 85.7% of the COVID-19 trials and 30.1% of T2DM trials had poor population representativeness. Conclusion This research demonstrates the potential of using the EHR data to assess the clinical trials population representativeness, providing data-driven metrics to inform the selection and optimization of eligibility criteria.

scholarly journals An Overview of CAR T Cell Mediated B Cell Maturation Antigen Therapy

2021 ◽  
Author(s):  
Sameer Quazi
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cell ◽  
Bispecific Antibody ◽  
Plasma Cells ◽  
Car T Cell ◽  
B Cell Maturation ◽  
Car T ◽  
Value Association ◽  
Made In

Multiple Myeloma (MM) is one of the incurable types of cancer in plasma cells. While immense progress has been made in the treatment of this malignancy, a large percentage of patients were unable to adapt to such therapy. Additionally, these therapies might be associated with significant diseases and are not always tolerated well in all patients. Since cancer in plasma cells has no cure, patients develop resistance to treatments, resulting in R/R MM. BCMA is primarily produced on mature B cells. Its up-regulation and activation are associated with multiple myeloma in both murine and human models, indicating that this might be an effective therapeutic target for this type of malignancy. Additionally, BCMA's predictive value, association with effective clinical trials, and capacity to be utilized in previously difficult to observe patient populations, imply that it might be used as a biomarker for multiple myeloma. Numerous kinds of BCMA-targeting medicines have demonstrated antimyeloma efficacy in individuals with refractory/relapsed MM, including CAR T-cell treatments, ADCs, bispecific antibody constructs. Among these medications, CART cell-mediated BCMA therapy has shown significant outcomes in multiple myeloma clinical trials. This review article outlines CAR T cell mediated BCMA medicines have the efficiency to change the therapeutic pattern for multiple myeloma significantly.

scholarly journals Perceptions of Community Hematologists/Oncologists on Barriers to Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Diffuse Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2198-2198
Author(s):  
Ajeet Gajra ◽  
Richard Sweat ◽  
Yolaine Jeune-Smith ◽  
Jonathan K. Kish ◽  
Bruce A Feinberg
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Annual Meeting ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The United States ◽  
Large B Cell Lymphoma ◽  
Car T

Introduction The ASH Annual Meeting is a venue for presentation of outcomes data from key clinical trials in hematologic malignancies and novel drug classes used to treat them. The approval of two CAR-T therapies, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel), in the treatment of large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL), has ushered in a new class of drugs, i.e. cellular therapy. At ASH 2018, Nastoupil et al. presented data from a retrospective analysis of the characteristics and outcomes of patients with relapsed/refractory LBCL, including DLBCL, treated with commercially available axi-cel CAR-T therapy at academic centers in the United States (Nastoupil LJ, et al. Blood. 2018;132[Suppl 1]:91). The authors found that early outcomes of real-world patients receiving axi-cel therapy were comparable to those observed in the clinical trial population, despite >40% of these patients failing to meet the clinical trial eligibility criteria. At a live meeting in February 2019, we sought the perceptions of community hematologists and oncologists (H/O) regarding their use of, referrals for and barriers to CAR-T therapy as well their perception of the value of the real-world evidence (RWE) presented. Methods A live meeting in February 2019 convened H/O with geographic representation from across the United States. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting and responded to questions regarding their perceptions of the data and its potential impact on current practice. Participants submitted their demographic responses via a web-based survey prior to the meeting and data impression responses via an audience response system at the live meeting. Results Among the 59 H/O who participated in this live market research program on February 22-23, 2019, 61% identified their primary specialty as hematology/oncology and 34% medical oncology. Only 27% of H/O had attended the 60th ASH Annual Meeting in December 2018. The participants were mostly community-based physicians, 50% in private community and 45% in community practices owned by a hospital or academic center. One-third have been in practice for over 20 years, one-third for 11-20 years and one-third for 10 or fewer years. This group sees an average of 20+ patients per day and reported B-cell non-Hodgkin lymphoma as one of the three most common hematologic malignancy they managed. 28% of H/O indicated that they have referred one patient and 24% have referred 2-5 patients for CAR-T therapy since the first approval on August 30, 2017. Of those H/O who had referred patients for CAR-T therapy, 45% indicated that none of their patients had yet received the infusion. The top two barriers to prescribing/recommending CAR-T therapy, as reported by the H/O, were the cumbersome logistics of administering therapy and following patients (52%), and the cost of the therapy (46%). Other concerns included high toxicity (24%) and lack of long-term survival data (19%), but not lack of knowledge of CAR-T therapy (2%). Furthermore, 87% of H/O agreed with the assertion that due to the limitations of randomized clinical trials, RWE is necessary to inform clinical practice. After review of the information presented on the real-world use of axi-cel, 73% of H/O indicated that this information is likely to cause them to recommend CAR-T therapy for more of their patients with DLBCL. Conclusions There is significant interest in adopting and using CAR-T therapies in LBCL amongst community H/O. This group does not perceive itself as lacking in knowledge regarding CAR-T therapy. The significant barriers of logistics and cost are potential deterrents to appropriate use. These results can inform stakeholders (manufacturers, payers, hospitals and practices) regarding the need to improve processes and develop payment models to address cost in order to facilitate access of these agents to the appropriate patients. RWE is viewed favorably by the vast majority of community H/O to inform clinical practice, due to the limitations of randomized clinical trials. Disclosures Gajra: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

scholarly journals Efficacy of Subsequent Therapies in Multiple Myeloma Patients after Progression on a BCMA Targeting Therapy: A Single-Center Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-13
Author(s):  
Barry Paul ◽  
Myra Robinson ◽  
Kristen Cassetta ◽  
Daniel Slaughter ◽  
Jordan Robinson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Research Funding ◽  
Subsequent Treatment ◽  
Single Center ◽  
Targeting Therapy ◽  
Single Center Experience ◽  
Best Response ◽  
Car T

Background: Targeting B-cell maturation antigen (BCMA) with antibody-drug conjugates (ADCs), bispecific antibodies, or chimeric antigen receptor t-cells (CAR-Ts) has proven safe and effective in recent clinical trials, but relapses remain common. As most patients treated with BCMA targeting therapies are refractory to conventional anti-myeloma therapies, management of these patients poses unique challenges once they progress, with no data available to guide subsequent therapies. Methods: We performed a retrospective chart review of all relapsed refractory multiple myeloma (RRMM) patients at our institution who progressed while on or after a BCMA targeting therapy and were treated with subsequent therapies. We evaluated the best response achieved and overall survival (OS) measured from progression on BCMA targeting therapies. Kaplan Meier methods were used to estimate OS curves and landmarks between classes of BCMA targeting therapy received (ADC, bispecific antibody or CAR-T), and by type of subsequent therapy. Results: At a median follow up of 6 months, a total of 47 patients were treated with a BMCA targeting therapy. Of those, a total of 21 (44.7%) patients have progressed, with 18 (38.3%) receiving another therapy. Twelve-month overall survival of the patients who received a subsequent treatment was 51.1% (figure 1a), but varied considerably based on the class of BCMA therapy they received (figure 1b). Patients who progressed after a BCMA CAR-T had the best OS (N =2, 6 mo OS: 100%, 12 mo OS: Of the 18 patients who progressed and were treated with subsequent therapies, 7 (38.9%) received 2 lines of therapy, 5 (27.8%) received 3 lines of therapy, and 1 patient (5.6%) received 5 lines of therapy. In the first relapse, 4 (22.2%) patients received infusional chemotherapy with CAR-D PACE or CAR-DCEP, 4 (22.2%) received the combination of elotuzumab, pomalidomide, and dexamethasone (Elo-Pd; one of which was first treated with CAR-DCEP), 3 (16.7%) received selinexor based regimens. The best response seen after first-line post BCMA treatment was a partial response (PR) in 5 (27.8% of patients), whereas 8 (61.5%) patients who received second-line treatment post-BCMA therapy had a PR or better, including 3 (23.1%) who had a very good partial response (VGPR). In the third line post-BCMA, 1 (16.7%) had a VGPR, while 1 (16.7%) had stable disease as their best response. The use of Elo or Dara after anti-BCMA progression seemed to correlate with improved OS (see figure 1c below). While all these patients were Elo naïve, the majority (94.4%) were previously Dara exposed. Conclusions: Our data demonstrate that many RRMM patients who progress on BCMA targeting therapies still derive benefit from subsequent treatment. Early evidence from our experience suggests a survival advantage with monoclonal antibody-based therapies even in patients who had previously been exposed to these agents-suggesting a possible resensitization with BCMA directed therapy. Although our dataset is a single-center experience, to our knowledge it represents the first report of post-BCMA exposed management of RRMM and provides valuable insight into the treatment of this challenging and ever-expanding population. Disclosures Paul: Bristol-Myers Squibb: Other: Stock Ownership (prior employee); Amgen: Consultancy, Speakers Bureau; Regeneron: Membership on an entity's Board of Directors or advisory committees. Bhutani:BMS: Other: Clinical trial funding to institute, Speakers Bureau; Takeda: Other: Clinical trial funding to institute, Speakers Bureau; Prothena: Other: Clinical Trial Funding to Institute; Amgen: Speakers Bureau; MedImmune: Other: Clinical Trial Funding to Institute; Sanofi Genzyme: Consultancy; Janssen: Other: Clinical Trial Funding to Institute. Voorhees:Adaptive Biotechnologies: Other: Personal fees; Bristol-Myers Squibb: Other: Personal fees; Celgene: Other: Personal fees; Janssen: Other: Personal fees; Novartis: Other: Personal fees; Oncopeptides: Other: Personal fees; TeneoBio: Other: Personal fees; Levine Cancer Institute, Atrium Health: Current Employment. Usmani:Celgene: Other; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Array Biopharma: Research Funding; GSK: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Atrash:BMS, Jansen oncology, Sanofi: Speakers Bureau; Takeda, Amgen, Karyopharm, BMS, Sanofi, Cellactar, Janssen and Celgene: Honoraria; Amgen, GSK, Karyopharm.: Research Funding.

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