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Clinical efficacy of enfortumab vedotin-pembrolizumab (EV-P) in locally advanced (LA) or metastatic urothelial carcinoma (mUC): A real-world retrospective study.
Jain, Prateek , Naqvi, Syed Arsalan Ahmed , Anjum, Muhammad Umair , Afzal, Muhammad Umar, Yum, Ji-Eun Irene, Warraich, Kainat , Jajja, Salman Ayub, Swati, Fnu, Tripathi, Nikita , Orme, Jacob J. , Tyson, Mark D. , Yu, Nathan Y. , Jain, Prateek, Khan, Muhammad Ali , Afzal, Muhammad Umar, Childs, Daniel S. , Zakharia, Yousef , Riaz, Irbaz Bin , Singh, Parminder Pal

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 745-745

10.1200/jco.2025.43.5_suppl.745 Get It

745 Background: The combination of EV-P therapy has recently been approved as first-line (1L) therapy for patients with LA/mUC based on the results of the EV-302 trial. Herein, we report the updated results from a cohort of patients with LA/mUC who received EV-P in real world clinical setting. Methods: This retrospective study included patients with LA/mUC (07/2022-08/2024) at the Mayo Clinic who completed at least one cycle of EV-P. The best overall response (BOR) was evaluated using radiographic imaging and was adjudicated as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), or progressive disease (PD). The median progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death, was estimated using the Kaplan-Meier method. Patients who had not experienced disease progression by their last follow-up were censored for the PFS analysis. Results: A total of 120 patients were included; 79 (65.8%) were males, 41 (34.1%) females, 109 (91%) White, and 119 (99%) were non-Hispanic/Latino. The median age was 72 years (IQR: 65-77). Of these, only 22 (18.3%) had locally advanced disease while the remaining had mUC; 62 (51.6%) had lower tract urothelial carcinoma (LUTC), 36 (30%) had upper tract urothelial carcinoma (UTUC). The median follow-up time was 7.1 months (IQR: 4.93-9.26). In terms of BOR, 56 patients (46.6%) experienced PR, 34 (28.3%) CR, 12 (10%) PD, 7 (5.8%) MR, and 8 (6.6%) experienced SD. 3 (2.5%) patients were not evaluable. The BOR across subgroups, LA and mUC, including LUTC and UTUC, is summarized in the table. Among the responders, the median number of treatment cycles to first response was 3 (IQR: 2.25–4). Within the follow-up, 28 patients (23.3%) experienced eventual radiographic disease progression; death was observed in 25 patients (20.8%). The median PFS was 12.7 months (95% CI: 9.8-NE), and OS was 25.1 months (16.3-NE). Conclusions: In real world setting, the combination of EV-P in LA/mUC demonstrated clinical efficacy compatible with the findings from the EV-302 trial. Our results showed comparable efficacy with EV-P in both UTUC and LUTC, highlighting it's broad therapeutic potential. However, clinical data at longer follow-up is required to fully evaluate overall survival and the durability of response. mUC LA Overall LUTC UTUC Total patients 98 62 36 22 BOR CR 23 (23.4%) 13 (20.9%) 10 (28.5%) 11 (50%) PR 49 (52.6%) 31 (50%) 18 (50%) 7 (31.8%) SD 6 (6.4%) 2 (3.2%) 4 (11.4%) 2 (9.0%) PD 10 (10.7%) 9 (15.5%) 1 (2.8%) 2 (9.0%) MR 7 (7.5%) 5 (8.6%) 2 (5.7%) 0 (0%)
Inferring ECOG performance status (PS) using large language models in patients with advanced prostate cancer.
Raina, Ammad, Muniz, Miguel, Anjum, Muhammad Umair , Ayub, Umair , Naqvi, Syed Arsalan Ahmed , Jajja, Salman Ayub, Yum, Ji-Eun Irene, Yu, Nathan Y. , Abdul‐Muhsin, Haidar , Sartor, Alton Oliver, Orme, Jacob J. , Zhou, Ben , Singh, Parminder Pal , Zakharia, Yousef , Childs, Daniel S. , Riaz, Irbaz Bin

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 136-136

10.1200/jco.2025.43.5_suppl.136 Get It

136 Background: The ECOG performance status (PS) is a critical measure for evaluating functional capacity and determining clinical trial eligibility in patients with advanced prostate cancer. We aim to assess the capability of large language models (LLMs) to accurately infer ECOG PS from unstructured oncology notes. Methods: This retrospective study included patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177–PSMA-617 ( 177 Lu) at the Mayo Clinic (2022-2023). Baseline ECOG PS scores were manually curated by a trained clinician from clinical notes recorded within four weeks prior to 177 Lu initiation. Structured zero-shot prompts were then used to prompt GPT-4 to infer ECOG PS scores from unstructured oncology notes. Total dataset was randomly sampled to prompt development (20%) and held-out test set (80%). Three experimental setups were employed to assess model performance: (i) utilizing unmasked clinical notes, (ii) clinical notes with only numerical ECOG PS scores masked while retaining narrative descriptive/assessment by oncologist of ECOG score, and (iii) clinical notes with both numerical scores and narrative ECOG descriptors masked. Final performance was assessed using evaluation metrics (precision, recall, F1 score) on the held-out test set. Results: A total of 240 patients (n: 50 prompt development; n: 190 test set) were included in the analysis. The median age was 70 (IQR: 66-76); a majority of patients were White (n: 229; 95%) and non-Hispanic (n: 233; 97%). The most prevalent ECOG PS score was 0 (n: 140; 58%), followed by 1 (n: 88; 37%), and 2 (n: 12; 5%). The performance was numerically higher when using unmasked notes (weighted average precision: 0.89; recall: 0.89; F1: 0.89), compared to using notes with masked scores only (weighted average precision: 0.76; recall: 0.79; F1: 0.75) and notes with both scores and narrative masked (weighted average precision: 0.57; recall: 0.53; F1: 0.48). Metrics by each ECOG PS score is outlined (Table). Conclusions: Large language models demonstrate significant potential in precisely extracting ECOG performance status from unstructured oncology notes, offering valuable support for treatment decision-making and clinical trial enrollment. However, model performance declines as reliance on implicit reporting within clinical notes increases. Future efforts focusing on prediction of ECOG using a series of notes over time will be the next step. ECOG Unmasked oncology notes ECOG Score masked only ECOG Score + ECOG narrative marked Precision Recall F1 Score Precision Recall F1 Score Precision Recall F1 Score 0 0.89 0.92 0.91 0.75 0.93 0.83 0.59 0.74 0.66 1 0.88 0.86 0.87 0.76 0.74 0.75 0.19 0.47 0.27 2 1.00 0.82 0.90 0.78 0.33 0.47 0.78 0.16 0.26
Survival in advanced prostate cancer (PCa) patients with visceral metastasis: A population-based SEER study.
Jajja, Salman Ayub, Naqvi, Syed Arsalan Ahmed , Afzal, Muhammad Umar, Anjum, Muhammad Umair , Raina, Ammad, Swati, Fnu, Riaz, Zaryab Bin, Cobran, Ewan K. , Khan, Muhammad Ali , Afzal, Muhammad Umar, Jain, Prateek, Childs, Daniel S. , Bryce, Alan H. , Zakharia, Yousef , Singh, Parminder Pal , Riaz, Irbaz Bin

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 134-134

10.1200/jco.2025.43.5_suppl.134 Get It

134 Background: Prostate cancer patients with visceral metastases at diagnosis are often treated using one-size-fits-all approach. For example, CHAARTED criteria treats any visceral metastasis as high volume. Therefore, we aimed to assess overall survival (OS) by site of visceral involvement in patients with metastatic PCa. Methods: Surveillance, Epidemiology, and End Results (SEER) database (2010-2021) was queried to obtain case listing data on metastatic PCa patients from 17 registries. The patients were categorized into three groups based on visceral metastasis at diagnosis: lung metastasis, liver metastasis, and others. Kaplan-Meier survival analysis was performed to estimate median OS with 95% confidence interval (CI). Log-rank test was conducted to assess if survival was significantly different among the groups. Cox proportional hazard regression analysis was performed to assess the magnitude of difference among the groups. P-value <0.05 established statistical significance. Results: This analysis included 21,007 metastatic PCa patients (lung: n=319; liver: n=123; brain: 107; bone: 20538). Metastatic PCa population with lung metastasis exhibited a median OS of 60 months (95% CI: 48-72) compared to 24 months (95% CI: 12-36) in population with liver metastases and to 36 months (95% CI: 36-36) in population with other metastases. The difference in OS among the groups was statistically significant (p < 0.001). Compared to population with lung metastasis, those with liver (HR: 1.91; 95% CI: 1.41-2.57) but not those with other metastases (1.16; 0.97-1.39) had significantly worse OS adjusting for Gleason score, PSA and race (Table). Conclusions: In metastatic PCa, patients with lung-only metastasis have significantly better overall survival and should be considered differently in prognostication to liver metastases. Consideration of site of visceral metastasis is critical for treatment intensification decisions. Limitations of this analysis include lack of accounting for confounding relationships at individual patient level. Variable Hazard Ratio (95% CI) Metastases (Lung) REFERENCE Metastases (Liver) 1.91 (1.41-2.57) Metastases (Other) 1.16 (0.97-1.39) Gleason score≥8 REFERENCE Gleason score <8 0.68 (0.64 -0.72) PSA - ng/dL 1.01 (1.00 – 1.01) Race (White) REFERENCE Race (Black) 0.99 (0.94 – 1.05) Race (Asian or Pacific Islander) 0.70 (0.64 – 0.76)
Assessment of pathologic responses from unstructured pathology reports using large language models.
Popli, Swati, Anjum, Muhammad Umair , Naqvi, Syed Arsalan Ahmed , Popli, Swati, Jain, Prateek, Singh, Parminder Pal , Zakharia, Yousef , Riaz, Irbaz Bin

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 866-866

10.1200/jco.2025.43.5_suppl.866 Get It

866 Background: Emerging data suggests that Language Models (LLMs) provide an unprecedented opportunity to extract critical data from the unstructured pathology reports. However, the performance of state of art (SOTA) models on clinically meaningful tasks such as assessment of pathologic responses in patients receiving neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer(MIBC) is not well known. Methods: This retrospective cohort included patients with pathologically confirmed Muscle-Invasive Bladder Cancer from the year 2018 to 2024. Selected patients included those who underwent Neoadjuvant chemotherapy followed by definitive cystectomy at Mayo Clinic. Gold standard labels were manually curated by trained clinicians. The state of the art (SOTA) LLM – GPT4 – was utilized using a structured zero-shot prompt to extract relevant phenotypic variables such as tumor site, tumor histology and additional histological variants if any, presence of in-situ / invasive carcinoma, presence of lamina propria / muscularis propria / lympho-vascular / perineural invasion, and T-stage from unstructured pathology reports. Structured prompts were iteratively developed for each data variable and validated using ~5% of the total dataset. The extracted variables were manually compared and labelled as True positive / True negative / False positive / False negative. Final performance was assessed against a held-out expert annotated test dataset using evaluation metric (accuracy). Results: A total of 200 reports from 99 patients were extracted by the LLM. Of the 200 reports, 41 duplicate / other pathology reports (e.g. – autopsy, cholecystectomy, etc.) were removed during final assessment. Significant characteristics such as tumor site, histology, and additional histology variant had an accuracy of 89%, 87%, and 91% respectively. Notably, accuracy of detection of in-situ versus invasive carcinoma was 70% versus 91%. Specific variables such as lamina propria / muscularis propria invasion / T-stage / lympho-vascular invasion / perineural invasion were answered with the accuracy of 75%, 75%, 67%, 90%, and 94% respectively. Conclusions: LLMs have the potential to extract critical data from unstructured pathology reports and automate assessment of pathologic responses in MIBC patients receiving NAC. Iterative improvements in performance can be achieved by improving prompt design using expert clinical input. This process can be potentially scaled to automate cancer registries.
Utilizing Large Language Models to Automate Prognostication in Patients with Myelofibrosis: A Retrospective Cohort Study
Khan, Muhammad Ali , Ayub, Umair , Anjum, Muhammad Umair , Jajja, Salman Ayub, Naqvi, Syed Arsalan Ahmed , Riaz, Zaryab Bin, Raina, Ammad, Palmer, Jeanne , Riaz, Irbaz Bin

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 1794-1794

10.1182/blood-2024-212366 Get It

Introduction Prognostication in myelofibrosis (MF) currently relies on manual assessment of clinical, pathological, and laboratory variables, which is inefficient and error-prone. The potential of large language models (LLMs) and rule-based programming to automate data extraction and prognostication in these patients remains unexplored and merits investigation. Methods Patients with MF were identified from a retrospective chart review. Data regarding clinical (age, constitutional symptoms, transfusion requirements), laboratory (hemoglobin, circulating white blood cell, platelet, and blast counts), and pathological (grade of bone marrow fibrosis, chromosomal analyses, cytogenetics) features was extracted from the latest free-text clinical notes and pathology reports using the generative pretrained transformer-4 (GPT-4) model in a zero-shot setting with the prompting parameters set to generate deterministic responses. The patients were randomly sampled into development (15%) and test (85%) sets, with the documents of patients in the development set used for iterative prompt engineering. The finalized prompts were used for data extraction in the test set. Rule-based programming was used for post-processing of the extracted data and ascertaining prognosis via Dynamic International Prognostic Scoring System (DIPSS), DIPSS-plus (DIPSS+), and Mutation-enhanced International Prognostic Scoring System-70 (MIPSS-70). Automatically extracted data and prognostic categories were compared with the manually generated human annotations. Mean accuracy, precision, and recall with 95% confidence intervals (CI) were computed. Detailed error and sensitivity analyses were conducted to assess performance. Results The study included 100 patients (development: 15; test: 85) with 100 clinical notes (development: 15; test: 85) and 90 pathology reports (development: 13; test: 77). The mean age of these patients was 70 (SD: 10.6); 55 (55%) patients were men, and 93 (93%) patients were White. In the development set, the mean accuracy, precision, and recall for data extraction from clinical notes were 94% (95% CI: 90-98%), 92% (84-99%), and 99% (97-100%). For data extraction from pathology reports, the mean accuracy, precision, and recall were 96% (93-100%), 98% (92-100%), and 83% (63-100%). For prognostication, the mean accuracy, precision, and recall were 87% (79-94%), 80% (73-87%), and 100% using DIPSS (accuracy: 80%; precision: 73%; recall: 100%), DIPSS+ (accuracy: 93%; precision: 83%; recall: 100%) and MIPSS-70 (accuracy: 87%, precision: 83%; recall: 100%). In the test set, the mean accuracy, precision, and recall for data extraction from clinical notes were 96% (95% CI: 93-98%), 91% (87-96%), and 98% (97-100%). For data extraction from pathology reports, the mean accuracy, precision, and recall were 95% (92-98%), 93% (87-99%), and 90% (80-100%). For prognostication the mean accuracy, precision, and recall were 95% (94-96%), 89% (88-90%) and 99% (96-100%) using DIPSS (accuracy: 94%; precision: 89%; recall: 100%), DIPSS+ (accuracy: 95%; precision: 88%; recall: 95%) and MIPSS-70 (accuracy: 94%, precision: 90%; recall: 100%). Error analyses identified incorrect extractions by GPT-4 were related to the circulating blasts and constitutional symptoms variables from the clinical notes. Sensitivity analyses excluding the associated variables improved overall accuracy from 94% to 97% and 96% to 97% in the development and test sets, respectively. Similarly, incorrect extractions from the pathology reports were related to the CALR gene mutation variables. Sensitivity analyses excluding the associated variables improved the overall accuracy from 96% to 98% and 95% to 97% in the development and test sets, respectively. Conclusion LLMs and rule-based programming can accurately extract data from the electronic health records and prognosticate MF patients via DIPSS, DIPSS+, and MIPSS-70. The automated approach could significantly streamline clinical and research workflows, providing an efficient and less resource-intensive alternative to manual prognostication.
Comparative Meta-Analysis of Triplet vs. Quadruplet Induction Regimens in Newly Diagnosed, Treatment Naïve, Multiple Myeloma
Paul, Barry , Raza, Shahzad , Mammadzadeh, Aytaj , Khasawneh, B. , Shatnawi, Sara, Ahmed, Nausheen , Mushtaq, Muhammad Umair , Atrash, Shebli , Raza, Shahzad , Khasawneh, Bayan , Ahmed, Nausheen , Atrash, Shebli , Paul, Barry , Anwer, Faiz , McGuirk, Joseph P. , Mahmoudjafari, Zahra , Abdallah, Al-Ola

Cancers | August 23, 2024 | Volume: 16 | Issue: 17 | Pages: 2938

10.3390/cancers16172938 | PMID 39272795 Get It

The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients.
Racial disparities in the intervention trials in colon cancer.
Vyas, Abhinav, Kaur, Dania, Savani, Saloni , Yadav, Udit, Batra, Akshee , Shahzad, Moazzam , Singh, Rohit , Yadav, Udit , Mushtaq, Muhammad Umair

Journal of Clinical Oncology | May 29, 2024 | Volume: 42 | Issue: 16_suppl | Pages: e13718-e13718

10.1200/jco.2024.42.16_suppl.e13718 Get It

e13718 Background: Colorectal cancer (CRC) is the third-leading cancer worldwide and racial minorities bear a disproportionate burden of this disease. Methods: We searched the clinicaltrials.gov database for all the completed clinical trials conducted on adult patients until 2023 in the United States. In intervention trials, we manually abstracted data on the racial distribution of enrollees, phases, tumor histology, intervention type, and year of completion. We divided interventions into chemotherapy, radiotherapy, surgery, immunotherapy, behavioral, diagnostic tests, and others. To quantify the racial disparity, we calculated the enrolment ratio (ER) as the observed ratios of racial participation in the study compared to the prevalence in colorectal cancer per the 2009-2019 Surveillance, Epidemiology and End Results (SEER) database. We also conducted subgroup racial enrollment based on clinical trial and type of intervention. Results: We identified 394 studies, of which 252 studies (64%) had racial distribution published, including 138814 participants. Most studies were phase 2 trials (168), followed by phase 1/2 trials (49) and phase 3 studies (43). The racial breakdown included 88677 White participants (63.9%), 23230 were African Americans (16.7%), 9963 were Asians (7.1%), 4398 were of other races (3.2%), and 12546 were of unknown race (9.0%). The frequency of including racial data was 100% in Phase 1 studies, 56.5% in Phase 2, 58.1% in Phase 3, and only 16% in Phase 4. A total of 185 were immunotherapy trials, out of which 63 studied chemotherapies, radiotherapy and/ or surgery along with immunotherapy. Racial enrolment data was reported in 68.6 %, 58% and 59.3% in immunotherapy, chemotherapy, and radiotherapy interventions respectively. The ERs of whites, blacks, and Asians were 0.8, 1.3, and 0.9, respectively (Table). However, ER in subgroups with specific interventions, such as chemotherapy, immunotherapy, and radiotherapy, were 0.5, 0.4, and 0.6, respectively. Conclusions: African Americans are underrepresented in CRC intervention trials. Equal access and tailored strategies for cultural and linguistic differences are needed for fair participation. [Table: see text]
Global Access to Multiple Myeloma Medications (GLAMM-2 Study): Access and Barriers to Chemoimmunotherapies and Transplant
Mammadzadeh, Aytaj , Shatnawi, Yara, Atallah, Rawan , Mohamed, Benlazar, Hashmi, Shahrukh K. , Carneiro, Thiago Xavier , Shaikh, Hira , Strouse, Christopher , Popat, Rakesh , Mushtaq, Muhammad Umair , Strouse, Christopher S , Shaikh, Hira , Desai, Nihar , Popat, Rakesh , Mahmoudjafari, Zahra , Abdallah, Al-Ola , Ahmed, Nausheen

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 4727-4727

10.1182/blood-2023-185151 Get It

Introduction Multiple myeloma (MM) is a clonal plasma cell malignancy and is the second most common type of hematologic cancer worldwide. Treatment options for MM have evolved in the last two decades with the introduction of novel therapeutic agents such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PI), anti-CD-38 monoclonal antibodies (anti-CD38 MoAb), and recently BCMA-directed therapies (BDT). The variable access globally, especially for novel agents, has been a concern. We aim to study the global availability of 14 chemoimmunotherapy options in addition to autologous stem cell transplant (ASCT) which is approved in the US (excluding BDT due to limited availability), to identify regions with restricted access and analyze the main barriers to access. Methods A global cohort of oncologists outside the USA who treat MM participated in an online survey to evaluate the patterns of accessibility of MM therapies worldwide. The survey, conducted in collaboration with the US Myeloma Innovations Research Collaborative (USMIRC), was sent electronically to 176 oncologists worldwide (outside the US) from June 18th, 2023, to July 17th, 2023. It included questions on demographics, access, and perceived barriers. The respondents chose a response for each therapy as being “easily accessible”, “moderately accessible,” “not readily accessible” or “no access”. Countries were then classified as having “adequate access” if 80-100% of respondents affirmed easy/moderately easy access, while &lt;30% were considered “limited access”, 60-79% were “high-intermediate access” and 30-59% were “low-intermediate access”. We classified countries into low- and high-income (LIC and HIC) based on the United Nations (UN) World Economic Classifications based on per capita gross national income (GNI). Means were calculated for regions of interest. An interim analysis is reported. Results Demographics: Ninety-Five (54%) oncologists from 33 countries completed the survey. Most were from Asia (56%). Others were Europe (19%), South America (12%), Africa (7%), Oceania (3%), and North America (Canada and Mexico, excluding the US) (3%). Only 17% specialized in plasma cell disorders; 50.5% were affiliated with university academic centers; 18% with private or community practices; 12% with community academic centers; and 17% were hybrid. Public-funded centers represented 61.1%, while 76% were transplant centers. Global Patterns: Most countries had adequate access to chemotherapies, IMiDs, PIs, Anti-CD38, MoAbs, and ASCT (Figure 1). Notably, ixazomib, isatuximab, and selinexor had low intermediate access, while elotuzumab had limited access. Access by Income: Most MM therapies were available in LIC and HIC. Of the therapies listed, 6 were adequately available in LIC and HIC: cyclophosphamide, lenalidomide, pomalidomide, daratumumab, bortezomib, and ASCT (Table 1). Elotuzumab and selinexor were limited in both LIC and HIC. Ixazomib and isatuximab were also limited in LIC but were low-intermediate in HIC. Access by Continent: Out of the 14 therapies, Europe had adequate or high-intermediate access to most modalities (12), followed by Oceania and Asia (10), and South America (9). North America and Africa had the lowest number of adequate or high intermediate access therapies (7) (Table 1). Barriers: The most common reason cited for limited access to MM therapies globally was the financial burden for the healthcare system, followed by limitations in local agency approval, inadequate chemotherapy suite resources, and inadequate staffing. Conclusion While most therapies were available, novel therapies such as isatuximab, ixazomib, selinexor, and elotuzumab were less readily accessible. Moreover, North America and Africa had the least access to therapies. This is likely because LIC and HIC have prioritized access to treatments with the best evidence of cost-effectiveness, while those with lower cost-effectiveness are generally limited. The financial burden on healthcare is a major limiting factor. USMIRC plans to investigate potential solutions and pursue global collaborative efforts to reduce disparities in therapies.
Efficacy of Daratumumab-Based Regimens in Anti-CD38 Treatment-Naïve Relapsed/Refractory Multiple Myeloma with High-Risk Cytogenetics
Mansour, Razan , Mammadzadeh, Aytaj , Hashmi, Hamza , Afrough, Aimaz , Alkharabsheh, Omar , Paul, Barry , Mushtaq, Muhammad Umair , Skikne, Barry, Snyder, Jordan Andrew , Atrash, Shebli , Ahmed, Nausheen , Abdallah, Al-Ola

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 1985-1985

10.1182/blood-2023-187487 Get It

Background: Daratumumab-based combination with proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs) have revolutionized the treatment outcomes of relapsed/refractory multiple myeloma (RRMM). Several daratumumab-based triplet combinations have been approved for the management of RRMM, but outcomes of daratumumab-based triplets in patients with high-risk cytogenetics RRMM (HC-RRMM) are not well described in the literature. This study aimed to evaluate the clinical outcome of daratumumab-based regimens in patients with HC-RRMM who are daratumumab-naïve. Methods: A retrospective review of 110 patients with HC-RRMM who received daratumumab-containing regimens from 6/2016 through 2/2023 at the University of Kansas Medical Center, in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC) was conducted. Daratumumab was combined with bortezomib/dexamethasone (DVd), carfilzomib/dexamethasone (DKd), and pomalidomide/dexamethasone (DPd) for treatment of RRMM. HC-RRMM was defined as patients with one or more cytogenetic abnormalities (on FISH panel) including -17/del(17p), t(4;14), t(14;16), t(14;20), or amplification of 1q. Responses to therapy including overall response rate (ORR), complete response or better (≥CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. Descriptive statistics were used to summarize patient and disease characteristics, along with efficacy outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier methods. Results: Of the 110 patients with HC-RRMM, the median age was 66 years (range 43-84), 83 (75%) were Caucasian, 60 (54%) had IgG isotype, 41 (37%) had revised international staging system (R-ISS) stage III disease, 35 (32%) had extramedullary disease (EMD), 57 (52%) patients had one high-risk cytogenetic (HC) abnormality, 49 (44%) had 2 HC abnormalities, while four (4%) had 3 HC abnormalities. The median number of previous lines of therapy was 2 (1-4). Eighty-eight patients (80%) were lenalidomide refractory, while 53 patients (48%) had double refractory disease to both a PI and IMiD treatment. A total of 19 (17%), 27 (25%), and 64 (58%) patients received DVd, DKd, and DPd, respectively. The overall response rate (ORR) for the entire patient population was 73%, 45% had VGPR or better, and 35% achieved ≥CR. Median follow-up was 28 months (12.07-53.57), the median OS was 28 months (95% CI 23.2 - 43.9) and PFS was 8.03 months (95% CI 5.8 - 12.2) for all treatment groups. The median PFS for 1 HC vs ³ 2 HC was 14.8 vs 4.57 months (HR 1.72, 95%CI 1.17-2.72 p = 0.006), respectively. Similarly, median OS for 1 HC vs ³ 2 HC was 43.93 vs 22.47 months (HR 1.87, 95%CI 1.15-3.05, p = 0.011), respectively. (Figure 1). On multivariate analysis, R-ISS stage III, -17/del(17p), and the presence of more than one HC abnormality were associated with poor OS. The most common cause for treatment discontinuation was progressive disease, accounting for 73% of patients in the whole cohort. As for each daratumumab-based triplet, discontinuation due progression occurred in 78%, 48%, and 83% in DVd, DKd, and DPd, respectively. Other causes of discontinuation included &gt; grade 3 neuropathy, which occurred in 16% of patients receiving DVd, and cardiac events, which occurred in 11% of patients receiving DKd. Treatment-related mortality occurred in 2% of patients in the whole cohort. At the time of evaluation, 14 patients remain on treatment. Conclusion: Advanced stage R-ISS disease at diagnosis, presence of -17/del(17p), and 2 or more HC abnormalities were associated with poor prognosis reflected by worse PFS and OS in HC-RRMM treated with daratumumab-based therapies. A larger cohort or a prospective study in patients with HC-RRMM is needed to compare long-term outcomes between daratumumab-based therapies (DKd, DVd, and DPd).
The GLAMM1 Study - Global Access to Myeloma Medications: Potential Barriers to Chimeric Antigen Receptors (CART) and T-Cell-Engaging Bispecific Antibodies (TCE) Globally
Atallah, Rawan, Shatnawi, Yara , Mammadzadeh, Aytaj , Hashmi, Shahrukh K. , Rana, Shabeeha, Mushtaq, Muhammad Umair , Mohamed, Benlazar, Carneiro, Thiago Xavier , Popat, Rakesh , Atallah, Rawan , Desai, Nihar , Popat, Rakesh , McGuirk, Joseph P. , Atrash, Shebli , Mahmoudjafari, Zahra , Abdallah, Al-Ola , Ahmed, Nausheen

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 3327-3327

10.1182/blood-2023-179050 Get It

Introduction: Novel B cell maturation antigen (BCMA) directed therapies including chimeric antigen receptor- T (CART) such as idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have been approved since 2021. More recently in 2022, the first BCMA-directed T-cell-engager (TCE), teclistamab (tec), was also approved for the treatment of relapsed/ refractory multiple myeloma (RRMM). Unfortunately, limited access to these therapies worldwide appears to be a major challenge. This study aims to gain insight into the variation in access to these therapies, and barriers to access. Methods: This study was an electronic survey of 176 hematologists/oncologists in centers across the globe outside the USA who treat MM and was conducted in collaboration with US Myeloma Innovations Research Collaborative (USMIRC). The survey was distributed from June 18 th 2023, to July 15 th 2023. Sections included demographics of respondents, availability of drugs in the country, and barriers to access. The respondents categorized each medication as “easily accessible”, “moderately accessible,” “not readily accessible” or “no access”. To categorize a country/region as having “adequate access”, the cut-off was 60% of responders affirming easy/moderately easy access. We investigated whether higher healthcare spending in a country is associated with better drug accessibility. Health expenditure (HE) of a country's Gross domestic product (GDP) from the World Bank was utilized to categorize countries into two groups: “High healthcare investing nations” (HHIN), which included countries spending &gt;10% of their GDP on healthcare, while “Low healthcare investing nations” (LHIN) included countries spending &lt;10% on healthcare. An interim analysis is reported. Results: There were 95 (54%) completed responses from 33 countries. Most (51%) were university-based academic centers and only 17% were centers with a dedicated focus in plasma cell disorders. Only 17% reported adequate access to ide-cel and 16% to cilta-cel, while a limited, yet higher number of respondents had adequate access to tec (23%). Refer to Table 1 Access to CART (ide-cel and cilta-cel): Globally, only 3 of the 33 (9%) countries had access to ide-cel, cilta-cel or both (France, Morocco, Saudi-Arabia). All other countries had limited access. When grouped by continent, none of the continents had adequate access to CART. Both HHIN and LHIN countries had limited access to CART. Access to TCE (tec): Seven of the 33 (21%) countries had adequate access to tec (Switzerland, Netherlands, France, Portugal, Czech Republic, Morrocco, Saudi Arabia). All other countries had limited access. When grouped by continent, although Europe had the most access, none of the continents had adequate access to TEC. Both HHIN and LHIN countries had limited access to TCE, although relatively, TEC was more accessible compared to CART. Figure 1 summarizes access to CART and TCE Barriers to access: Other than Europe, the most common barrier for ide-cel, cilta-cel and tec was cited as financial burden for patients. Financial burden for patients as a top barrier for each of the products by continent was as follows: Asia (83%), South America (64%), Africa (71%) Australia (100%), and North America (100%). In Europe, for CART, financial burden remained a top barrier (50%) along with local agency approval (50% for ide-cel, 44% for cilta-cel). In Europe, the most cited barrier for TCE was the financial burden for patients (44%), while (33%) of oncologists reported no barrier to TCE. Reimbursement for CART and TCE in Europe requires phase 3 randomized controlled trial data, which is just emerging since 2022 for CART and relatively increased access may be due to the presence of compassionate use programs. Conclusion : The survey is the first attempt to highlight the significantly limited global access to novel therapies (ide-cel, cilta-cel, and tec) for the treatment of RRMM. All continents including HHIN had limited access to CART and TCE. Noticeably, CART is less accessible than TCE, even though approved earlier. The main barrier to both CART and TCE is reported as financial burden for patients. USMIRC in collaboration with oncologists worldwide, global agencies, governments, regulatory agencies, policymakers and industry partners, is planning to further explore restrictions to access to CART and TCE and strategies to overcome these barriers.