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Hashmi, Shahrukh K.

https://orcid.org/0000-0002-8914-7927

Mayo Clinic

Mayo Clinic

Citations 131

Delayed T-cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults
Perales, Miguel‐Angel , Riches, Marcie , He, Naya, Chemaly, Roy F. , Dandoy, Christopher E. , Hill, Joshua A. , Díaz, Miguel Ángel , Hashmi, Shahrukh K. , Prockop, Susan E. , Hildebrandt, Gerhard , Szabolcs, Paul , Hill, Joshua A. , Martens, Michael J , Chemaly, Roy F , Dandoy, Christopher E , Hill, Joshua A , Diaz Perez, Miguel Angel , Hashmi, Shahrukh K , Prockop, Susan E , Lazarus, Hillard M , Auletta, Jeffery J , Szabolcs, Paul , Perales, Miguel-Angel , Hill, Joshua A , Martens, Michael J. , Lazarus, Hillard M. , Beitinjaneh, Amer , Auletta, Jeffery J.

Blood Advances | April 18, 2025 | Volume: 9 | Issue: 14 | Pages: 3502-3517

10.1182/bloodadvances.2024015288 Get It

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T- and B-cell recovery have improved survival and decreased treatment-related mortality (TRM). A total of 2089 patients were included who underwent first allo-HCT for acute myeloid leukemia/acute lymphoblastic leukemia/myelodysplastic syndrome from 2008 to 2019 reported to the Center for International Blood and Marrow Transplant Research with available CD4 counts at days 100 and 180. Patients (median age, 51 years [range, 2-75]) were categorized into 4 groups based on graft-versus-host disease (GVHD) prophylaxis: ex vivo T-cell depletion (TCD/CD34), posttransplant cyclophosphamide, calcineurin inhibitor alone (CNI), or CNI with antithymocyte globulin. Based upon survival, we could identify optimal cutoff points for CD4+ T cells in pediatric (age of <20 years) patients: 248 × 106/L and 420 × 106/L at days 100 and 180, respectively; and in adult (age of >20 years) patients: 104 × 106/L and 115 × 106/L at days 100 and 180, respectively. In adults, day-100 CD4 count was associated with overall survival (OS), progression-free survival (PFS), and TRM but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cutoff point at day 180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.
UAE Consensus on Patient Profiles for Pre-exposure Prophylaxis with Monoclonal Antibodies against COVID-19 in Hematological Malignancies and Immunocompromised States
Hashmi, Shahrukh K. , Abdalla, Jehad , Alam, Arif, Abuhaleeqa, Mohamed , Mehiri, Amna Al, Lal, Amar , Osman, Hani, Kaloyannidis, Panayotis , George, Biju

New Emirates Medical Journal | April 10, 2025 | Volume: 05 | Issue: No issue available | Pages: No page available

10.2174/0102506882347591250115073949 Get It

Introduction: Despite significant advancements in COVID-19 treatment and prevention, immunocompromised individuals, particularly those with hematological malignancies, remain at high risk for severe infection and suboptimal vaccine response. Pre-exposure prophylaxis strategies for these vulnerable populations have been limited. Monoclonal antibodies, proteins designed to target specific antigens, offer a promising preventive solution for individuals unable to mount a sufficient immune response to vaccination. However, there is a critical unmet need to establish clear patient selection criteria for pre-exposure prophylaxis with monoclonal antibodies in these groups. This consensus statement explores recent research to address this gap, outlining profiles of patients most likely to benefit from monoclonal antibody-based prophylaxis. Methodology: The consensus statement was developed through a rigorous process, utilizing a pre-Delphi search method and a modified Delphi technique to gather expert opinions. This approach ensured a comprehensive and informed consensus among experts in the field. Initially, nine distinct patient categories requiring pre-exposure prophylaxis with monoclonal antibodies were identified. Through iterative rounds of expert feedback, discussion, and refinement, these nine categories were expanded and subdivided into twelve more specific groups of hematological malignancies and immunocompromised disorders. This refinement aimed to better capture the diverse patient profiles requiring prophylaxis, providing a more detailed framework for the targeted administration of monoclonal antibodies. Results: The study resulted in the panel members agreeing on nine categories for the use of monoclonal antibodies in COVID-19 prevention for high-risk patients. Achieving consensus among experts is crucial as it reflects the collective validation of evidence-based recommendations that can be reliably applied in clinical practice. A 100% agreement was reached for HIV and AIDS, underscoring the unanimous recognition of the vulnerability of this group to severe COVID-19 outcomes. Similarly, 96% agreement was reached for patients on immunomodulatory drugs (IMiDs), and 90.5% for those with hematological diseases, highlighting strong expert support for prophylaxis in these categories. Immunodeficiencies and renal conditions garnered 86% agreement, indicating broad, although slightly more varied, expert consensus on these groups. Lastly, 80% of the panel supported patients with solid organ cancer, liver conditions, rare neurological disorders, and severe life-limiting neuro-disabilities, reflecting recognition of their elevated risk despite more diverse opinions for these categories. Conclusion: This consensus statement offers healthcare professionals in the UAE a clear, evidence-based framework for the use of monoclonal antibodies in preventing COVID-19 among patients with hematological malignancies and immunocompromised conditions. By outlining specific patient categories, the statement provides a practical guide that enables clinicians to make informed decisions about pre-exposure prophylaxis, ensuring that high-risk individuals receive timely and appropriate protection. The consensus not only enhances the ability of healthcare providers to identify and prioritize at-risk populations, but also optimizes patient outcomes by streamlining preventive measures in clinical practice. In addition, these findings lay the groundwork for future research and the development of standardized protocols, ultimately improving the management of vulnerable populations in the ongoing fight against COVID-19.
Ocular graft host disease after allogeneic stem cell transplant: unique risk factors and outcomes
Fattah, Maaly A.M. Abdel, Elgohary, Ghada , Hashmi, Shahrukh K. , Fattah, Maaly Abdel Halim Mohamed Abdel

Delta Journal of Ophthalmology | June 27, 2024 | Volume: 25 | Issue: 2 | Pages: 73-81

10.4103/djo.djo_77_23 Get It

Objective The aim of this study was to formulate a retrospective study investigating the ocular findings and associated risk factors in long-term survivors after allogenic-hematopoietic stem cell transplantation (HSCT) in Saudi Arabia. Patients and methods This observational study was conducted on patients who underwent HSCT from 1996 to 2016 at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia. The study included 72 patients who were human leukocyte antigen-matched donors with identical matched sibling donors. Peripheral blood was the source of stem cells in 61 patients. The ophthalmological examination included visual acuity (VA) testing, refraction, tear break-up time, Schirmer’s test, slit-lamp biomicroscopy, and dilated ophthalmoscopy. Chronic ocular graft-versus-host disease (GVHD) inclusion was based on strict selection criteria. The patients identified with mild to moderate ocular GVHD had less than or equal to three corneal staining, 13–32 points ocular surface disease index (OSDI), and Schirmer’s test of 6–15 mm were classified as group 1, while those with severe ocular GVHD defined as having more than four corneal stainings, more than or equal to 33 points OSDI, and less than or equal to 5 mm Schirmer’s test were classified as group 2. Impairment of VA was classified as mild (20/22–20/50), moderate (20/70–>20/200), or severe (≤20/200) impairment. Results Chronic GVHD was diagnosed in 394 patients within the first 5 years after transplantation. Ocular GVHD was detected in 81 (20.56%) patients. They were classified into group 1 (65 patients, 80.25%) with mild to moderate ocular GVHD and group 2 (16 patients, 19.75%) with severe ocular GVHD. All patients had OSDI ranging from more than or equal to 13 to more than or equal to 33. Retinal changes were detected in five patients, optic disc changes in two patients, steroid-induced proliferative diabetic retinopathy in three patients, and old branch retinal vein occlusion in one patient. All patients with identical matched sibling donor showed normal or mild to moderate impaired VA except for two patients. All patients responded to topical eye drops except for nine who required surgical procedures. Normal or mild impaired VA was reported in 59 patients with statistical significance ( P =0.0053), while 42 male patients versus 29 females had normal or mild impaired VA with a statistically significant difference ( P =0.0179). Conclusion Ocular GVHD is a complex disease in our unique population. Every patient before allogenic HSCT be referred to a cornea specialist to evaluate the baseline parameters for the pre-HSCT diagnosis of dry eye disease.
Racial disparities in major adverse cardiovascular and cerebrovascular events in patients with non-Hodgkin lymphoma.
Chandani, Kanishka Uttam, Agrawal, Siddharth Pravin, Eldimllawi, Ahmed Medhat, Siddiq, Sajid, Hashmi, Shahrukh K. , Raval, Maharshi , Nadeem, Ahmed , Chintakuntlawar, Ashish V.

Journal of Clinical Oncology | June 10, 2024 | Volume: 42 | Issue: 16_suppl | Pages: e19076-e19076

10.1200/jco.2024.42.16_suppl.e19076 Get It

e19076 Background: Non-Hodgkin Lymphoma (NHL) is the seventh most prevalent cancer and has sixth highest malignancy mortality in United States. Owing to the advances in treatment of NHL including targeted therapies, the survival of NHL patients has increased over the past decades. However, inequalities may exist in the access to advanced care, clinical trials, and subspecialist appointments in certain patient populations. We aim to study the racial disparities in major cardiovascular and cerebrovascular events (MACCE) in NHL patients. Methods: Using ICD-10 codes, patients with NHL were identified from National Inpatient Sample 2019 database. We included all-cause in-hospital mortality (ACIHM), acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and sudden cardiac death (SCD) as MACCE for the outcomes. Baseline characteristics including demographics, comorbidities; and MACCE outcomes were studied using chi-square for categorical or ANOVA for continuous data (statistical significance determined as p-value <0.05) and results were stratified based on patient’s races. Results: Out of the total sample size of 205220 patients admitted with a diagnosis of NHL, 74.94% (153785) were White, 8.95% (18370) were Black, 9.46% (19415) were Hispanic, 3.48% (7140) were Asian/Pacific Islander, 0.42% (875) were Native American, while 2.75% (5635) belonged to other races. When compared to White patients, ACIHM was significantly higher in Black patients with adjusted odds ratio (aOR) of 1.294 (95% CI 1.099-1.523, p=0.002) and Asian/Pacific Islander patients (aOR 1.279, 95% CI 1.005-1.628, p=0.045). Risk of AMI was lower in Black patients (aOR 0.751, 95% CI 0.587-0.96, p=0.023) as compared to White patients. AF risk was significantly lower in Black, Hispanic, and Other race patients compared to White patients. The odds of developing CVA are higher in Asian/Pacific Islander patients (aOR 1.285, 95% CI 1.002-1.649, p=0.048) and of having SCD are higher in Black patients (aOR 2.052, 95% CI 1.5-2.806, p<0.001) when compared to White patients. Conclusions: In patients with NHL, Black patients had higher ACIHM and SCD while Asian/Pacific Islander patients had higher ACIHM and CVA when compared to White patients. Although the reason of disparity is likely multifactorial, the findings of this study highlight the need for development of healthcare strategies stratified by race which may aid to mitigate the increased risk of MACCE in certain races. Further research involving possible genetic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL becomes imperative.
Racial Disparities in Cardiovascular and Cerebrovascular Adverse Events in Patients with Non-Hodgkin Lymphoma: A Nationwide Analysis
Chandani, Kanishka Uttam, Agrawal, Siddharth , Raval, Maharshi , Siddiq, Sajid, Hashmi, Shahrukh K. , Agrawal, Siddharth Pravin , Nadeem, Ahmed , Chintakuntlawar, Ashish V.

Medicina | May 14, 2024 | Volume: 60 | Issue: 5 | Pages: 800

10.3390/medicina60050800 Get It

Background and Objectives: Non-Hodgkin lymphoma (NHL) has the sixth-highest malignancy-related mortality in the United States (US). However, inequalities exist in access to advanced care in specific patient populations. We aim to study the racial disparities in major adverse cardiovascular and cerebrovascular events (MACCEs) in NHL patients. Materials and Methods: Using ICD-10 codes, patients with NHL were identified from the US National Inpatient Sample 2016–2019 database. Baseline characteristics, comorbidities, and MACCE outcomes were studied, and results were stratified based on the patient’s race. Results: Of the 777,740 patients with a diagnosis of NHL, 74.22% (577,215) were White, 9.15% (71,180) were Black, 9.39% (73,000) were Hispanic, 3.33% (25,935) were Asian/Pacific Islander, 0.36% (2855) were Native American, and 3.54% (27,555) belonged to other races. When compared to White patients, all-cause mortality (ACM) was significantly higher in Black patients (aOR 1.27, 95% CI 1.17–1.38, p < 0.001) and in Asian/Pacific Islander patients (aOR 1.27, 95% CI 1.12–1.45, p < 0.001). Sudden cardiac death was found to have a higher aOR in all racial sub-groups as compared to White patients; however, it was statistically significant in Black patients only (aOR 1.81, 95% CI 1.52–2.16, p < 0.001). Atrial fibrillation (AF) risk was significantly lower in patients who were Black, Hispanic, and of other races compared to White patients. Acute myocardial infarction (AMI) was noted to have a statistically significantly lower aOR in Black patients (0.70, 95% CI 0.60–0.81, p < 0.001), Hispanic patients (0.69, 95% CI 0.59–0.80, p < 0.001), and patients of other races (0.57, 95% CI 0.43–0.75, p < 0.001) as compared to White patients. Conclusions: Racial disparities are found in MACCEs among NHL patients, which is likely multifactorial, highlighting the need for healthcare strategies stratified by race to mitigate the increased risk of MACCEs. Further research involving possible epigenomic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL is imperative.
Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities
Khera, Nandita , Brazauskas, Ruta , Patel, Jinalben , Üstün, Celalettin , Ballen, Karen K. , Abid, Muhammad Bilal , Díaz, Miguel Ángel , Al‐Homsi, A. Samer, Hong, Sanghee , Munker, Reinhold , Schears, Raquel M. , Ciurea, Stefan O. , Wirk, Baldeep , LeMaistre, Charles F. , Aljurf, Mahmoud , Sharma, Akshay , Černý, Jan , Kindwall‐Keller, Tamila L. , Winestone, Lena E. , Steinberg, Amir , Arnold, Staci D. , Seo, Sachiko , Preussler, Jaime M. , Hossain, Nasheed , Hashmi, Shahrukh K. , Lehmann, Leslie , Wood, William A. , Rangarajan, Hemalatha G. , Saber, Wael , Hahn, Theresa , Patel, Jinalben , Ustun, Celalettin , Abid, Muhammad Bilal , Diaz Perez, Miguel Angel , Hashem, Hasan , Ciurea, Stefan O , Badawy, Sherif M , Savani, Bipin N , LeMaistre, C Fred , Bhatt, Neel S , Sharma, Akshay , Cerny, Jan , Knight, Jennifer M , Kelkar, Amar H , Winestone, Lena E , Arnold, Staci D , Seo, Sachiko , Preussler, Jaime M , Hossain, Nasheed M , Fingrut, Warren B , Hashmi, Shahrukh K , Rangarajan, Hemalatha G , Wood, William A , Ailawadhi, Sikander , Jacobs, Benjamin, Hashem, Hasan , Lazarus, Hillard M. , Badawy, Sherif M. , Savani, Bipin N. , Bhatt, Neel S. , Beitinjaneh, Amer , Knight, Jennifer M. , Yared, Jean A. , Fingrut, Warren , Agrawal, Vaibhav

Blood Advances | April 25, 2024 | Volume: 8 | Issue: 13 | Pages: 3497-3506

10.1182/bloodadvances.2023012469 Get It

Abstract There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P &lt; .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.
Ovarian Tissue Cryopreservation versus Other Fertility Techniques for Chemoradiation-Induced Premature Ovarian Insufficiency in Women: A Systematic Review and Future Directions
Chaudhri, Eman N. , Salman, Ayman, Awartani, Khalid, Khan, Zaraq , Hashmi, Shahrukh K.

Life | March 15, 2024 | Volume: 14 | Issue: 3 | Pages: 393

10.3390/life14030393 Get It

Current advances in cancer therapy have increased survival, emphasizing the need for life quality improvement. Fertility loss is common post-chemotherapy. Current guidelines establish embryo and oocyte cryopreservation to address premature ovarian insufficiency (POI). Ovarian tissue cryopreservation has also recently become an acceptable option for fertility preservation, particularly as it is the only option for pre-pubertal patients. Few definitions for optimum fertility outcomes, and few systematic reviews comparing embryo, oocyte, and ovarian tissue cryopreservation as a means of fertility preservation (FP) in pre- and post-pubertal female cancer patients exist. This systematic review aims to improve understanding of gonadotoxic effects of chemoradiation therapy in cancer patients, to analyze the different fertility preservation techniques and procedures available to women with chemoradiation induced ovarian insufficiency, and to compare and recognize the benefits of each technique in restoring fertility, sexual hormone function, and quality of life. Searches were conducted electronically on PubMed, Cochrane, and EBSCOHost, including clinical trials, prospective, and retrospective studies of female cancer patients undergoing anti-cancer therapy, with predefined MeSH terminology. Data were collected, analyzed, and compared. Non-randomized clinical studies were evaluated for risk bias through the Newcastle–Ottawa Scale. In total, 23 studies were included. From there, 647 patients opted for oocyte cryopreservation, 267 for embryo cryopreservation, and 1382 for ovarian tissue cryopreservation (OTC). A total of 175, 18, and 121 live births resulted respectively from oocyte, embryo, and OTC, respectively. Studies without live births discussed other fertility markers as indicators of improvement in sexual hormone function and fertility. The gonadotoxic effects of chemotherapy call for FP intervention. Oocyte and embryo cryopreservation/implantation are well-established procedures. With changing trends and life quality consideration, OTC is a promising interventional method for pre-pubertal patients facing the prospect of fertility loss.
Ruxolitinib in Patients With Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of Efficacy and Safety From the Phase III REACH3 Study
Hashmi, Shahrukh K. , Musso, Maurizio , Uzay, Ant , Langmuir, Peter, Li, Xuechan, Gowda, Maanasa, Stefanelli, Tommaso , Zeiser, Robert , Russo, Domenico , Ram, Ron , Chakraverty, Ronjon , Middeke, Jan Moritz , Giebel, Sebastian , Hamad, Nada , Lee, Stephanie J. , Teshima, Takanori , Locatelli, Franco

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 654-654

10.1182/blood-2023-172590 Get It

Introduction: Corticosteroids (CS) are the standard first-line treatment for patients (pts) with chronic graft-versus-host disease (cGvHD), but pts can be unresponsive or become refractory to or dependent on CS (SR/D).Ruxolitinib (RUX), a JAK1/2 inhibitor, is approved for the treatment of pts ≥12 years of age with SR/D-cGVHD, based on the primary outcomes from the randomized, phase III REACH3 (NCT03112603) study, which demonstrated the superior efficacy of RUX vs best available treatment (BAT) in pts with SR/D-cGVHD. Here, we present the final, long-term efficacy and safety outcomes from REACH3. Methods: Pts ≥12 years of age with moderate or severe SR/D-cGVHD were randomized 1:1 to receive either RUX 10 mg twice daily (BID) or investigator-selected BAT and followed for 3 years, till discontinuation or death. The primary analysis was conducted at week 24 (Cycle 7 Day 1 [C7D1]) in randomized pts, then pts entered the extension period (C7-39) in which they continued treatment, switched from BAT to RUX (crossover cohort), or discontinued treatment and entered long-term survival follow-up (FU). Failure-free survival (FFS; key secondary endpoint), duration of response (DOR), overall survival (OS), non-relapse mortality (NRM), malignancy relapse (MR), and safety were analyzed at 3 years (week 156; final data cut off 15 Dec 2022). Overall response rate (ORR) and best overall response (BOR) during the crossover treatment period were analyzed for pts who switched from BAT to RUX on or after C7D1. Results: Of 329 pts randomized, 53 completed the treatment period and 276 discontinued, 115 entered survival FU (RUX: 73/165; BAT:42/164); 70 pts crossed over from BAT to RUX of which 16 completed the crossover treatment period and 24 entered survival FU. Median FFS was longer in the RUX vs BAT arms (38.4 vs 5.7 months; hazard ratio [HR]=0.361, 95% confidence interval [CI]: 0.268, 0.485) with 12-month FFS probabilities of 64.0% (95% CI: 56.1, 70.8) and 28.8% (95% CI: 21.8, 36.1), respectively. Median OS was not reached and there was no difference in risk of death between the arms (HR=0.851, 95% CI: 0.544, 1.331) [Table 1]. Median DOR was 6.4 months (95% CI: 4.9, 11.4) in the BAT arm but was not reached for the RUX arm; notably, the probability of maintaining DOR at 3 years was higher in RUX (59.6%; 95% CI: 50.4, 67.6) vs BAT (26.7%; 95% CI: 18.5, 35.5). NRM event rates were similar between the arms (RUX: 29/165; BAT 34/164), and MR events were similar and low in both arms (13/156 and 11/160, RUX and BAT respectively) up to 3 years. The ORR at week 24 after crossover from BAT to RUX was 50.0% (95% CI: 37.8, 62.2), including complete response (CR) in 4 (5.7%) pts and partial response (PR) in 31 (44.3%) pts. The BOR during crossover was 81.4% (95% CI: 70.3, 89.7), including CR of 7.1% and PR of 74.3%; disease progression only occurred in 1 pt. Almost all pts treated during the main treatment period (RUX: 100%; BAT: 93.7%) experienced ≥1 adverse event (AE) and, in general, AE rates were higher in the RUX vs BAT arms [Table 2], likely due to prolonged FU and exposure to RUX (median exposure to treatment of 52.9 weeks vs. 24.1 weeks for RUX and BAT, respectively).Anemia was the most common AE (RUX: 33.9%; BAT: 15.8%) and grade ≥3 AE for RUX (17.6% vs BAT 9.5%, respectively); grade ≥3 neutropenia, thrombocytopenia, alanine aminotransferase increase, and gamma-glutamyltransferase increase were also ≥5% higher for RUX than BAT. Anemia (24.2%; grade ≥3, 10.3%) and thrombocytopenia (3.8%) were the most common RUX and BAT treatment-related AEs, respectively. Infections, excluding tuberculosis, were the most common AE of special interest (77.6% vs. 68.4%; grade ≥3, 31.5% and 26.6%, for RUX and BAT, respectively). On-treatment deaths were mainly due to cGvHD (n/N, RUX: 10/18; BAT 6/12). Conclusions: After 3 years of treatment in REACH3, the longer FFS and higher DOR with RUX vs BAT indicated that cGVHD was more in control with RUX treatment. Notably, efficacy was demonstrated in pts who switched from BAT to RUX with an ORR similar to that in pts randomized to RUX. RUX was well tolerated with no unexpected toxicities and safety that was consistent with earlier studies. Overall, the long-term control of cGVHD and tolerability of RUX was demonstrated for pts ≥12 years of age with SR/D-cGvHD.
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.
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.