{"product_id":"car-t-cell-therapy-ide-cel-works-well-in-older-adults-with-multiple-myeloma-a-multicenter-real-world-study","title":"CAR T-Cell Therapy (Ide-cel) Works Well in Older Adults with Multiple Myeloma: A Multicenter Real-World Study","description":"\u003cp\u003eMultiple myeloma is a cancer that most often affects older adults, yet clinical trials of the latest treatments have not always included enough older patients to know how well these therapies work in this group. This real-world study of 156 patients across five US cancer centers found that a CAR T-cell therapy called idecabtagene vicleucel (ide-cel, brand name Abecma) was equally safe and effective in patients aged 65 years and older compared to younger patients, despite older patients having significantly more frailty, comorbidities, and other age-related health challenges. Older patients achieved an 86.7% overall response rate and a median overall survival of 26.5 months, with low rates of severe side effects. These findings suggest that chronological age alone should not disqualify older patients from receiving this powerful immunotherapy.\u003c\/p\u003e\n\n\u003ch1\u003eCAR T-Cell Therapy (Ide-cel) Works Well in Older Adults with Multiple Myeloma: A Multicenter Real-World Study\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eStudy Methods: How the Research Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#findings\"\u003eKey Findings: What the Researchers Discovered\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#safety\"\u003eSafety Profile: Side Effects in Older vs Younger Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#response\"\u003eTreatment Response: How Well Did Ide-cel Work?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#survival\"\u003eSurvival Outcomes: Progression-Free and Overall Survival\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#frailty\"\u003eFrailty and Geriatric Characteristics\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#comorbidities\"\u003eComorbidities and Clinical Trial Eligibility\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eClinical Implications: What This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What This Study Couldn't Prove\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations: Advice for Patients and Caregivers\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn a real-world study of 156 patients, ide-cel was equally safe and effective in those aged 65 and older compared with younger patients.\u003c\/li\u003e\n\u003cli\u003eOlder patients had an 86.7% overall response rate, 56% complete response rate, and median overall survival of 26.5 months.\u003c\/li\u003e\n\u003cli\u003eSevere cytokine-release syndrome occurred in 1% and severe neurotoxicity in 4% of older patients, with similar rates to younger patients.\u003c\/li\u003e\n\u003cli\u003e77.3% of older patients would not have qualified for the pivotal clinical trial, yet still achieved excellent outcomes.\u003c\/li\u003e\n\u003cli\u003eAge alone should not disqualify older patients from ide-cel therapy, but individual health factors and cardiac monitoring remain important.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003eMultiple myeloma (MM) is a cancer of plasma cells in the bone marrow. It is largely a disease of older persons, with the median age at diagnosis being 69 years. Among newly diagnosed patients, approximately two-thirds are over age 65, and one-third are over age 75. Projections suggest that within 15 years, nearly 3 out of 4 people newly diagnosed with multiple myeloma will be between the ages of 65 and 84.\u003c\/p\u003e\n\n\u003cp\u003eResearch over the past two decades has produced several newer treatment options for multiple myeloma, leading to substantial improvements in outcomes. However, these benefits have been disproportionate, favoring younger patients more than older ones. Outcomes with novel approaches have been inferior for septuagenarians (those aged 75 years and older) and poorer still for octogenarians (those aged 80 years and older). In fact, the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program has reported that about 19% of myeloma-related deaths occur in patients under age 65, while approximately 80% occur in patients aged 65 years and older.\u003c\/p\u003e\n\n\u003cp\u003eThe poorer outcomes in older patients may be multifactorial, including aging-related changes. An increase in frailty, comorbidities (other health conditions), and physical disabilities with age makes managing multiple myeloma in older patients challenging. The use of novel immunotherapies such as chimeric antigen receptor (CAR) T-cell (CART) therapy is especially challenging in this patient population.\u003c\/p\u003e\n\n\u003cp\u003eCAR T-cell therapy is a personalized treatment in which a patient's own immune cells (T cells) are collected, genetically modified to recognize and attack cancer cells, and then infused back into the patient. Idecabtagene vicleucel (ide-cel, sold under the brand name Abecma) was approved by the US Food and Drug Administration (FDA) for relapsed and refractory multiple myeloma based on the pivotal phase 2 KarMMa clinical trial. That study reported approximately a 70% overall response rate (ORR) in younger patients (under age 65; n=83) and 85% in older patients (aged 65 and older; n=45). The complete remission (CR) rate was about 30% for both age groups.\u003c\/p\u003e\n\n\u003cp\u003eHowever, because of stringent eligibility criteria, the KarMMa patient population was a highly selective group, and those results may not represent what happens in real-world clinical practice. Older patients in particular may be excluded from clinical trials due to comorbidities, organ dysfunction, or poor performance status. This study was designed to address that gap by examining real-world outcomes in older patients receiving commercial ide-cel, including detailed assessments of frailty and geriatric characteristics.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eStudy Methods: How the Research Was Conducted\u003c\/h2\u003e\n\n\u003cp\u003eThis was a multicenter, retrospective study conducted at 5 US institutions. The participating institutions included The University of Texas MD Anderson Cancer Center, H. Lee Moffitt Cancer Center and Research Institute, Stanford University School of Medicine, Cleveland Clinic Taussig Cancer Center, Atrium Health\/Wake Forest University School of Medicine (Levine Cancer Institute), and The University of Kansas Medical Center.\u003c\/p\u003e\n\n\u003cp\u003eData were collected for all patients who underwent leukapheresis (the process of collecting white blood cells for CAR T-cell manufacturing) followed by ide-cel infusion by August 31, 2022. Follow-up after infusion continued until November 2023. The median follow-up duration was 14.2 months.\u003c\/p\u003e\n\n\u003cp\u003eResearchers collected baseline characteristics including demographics, disease characteristics, prior treatments, time between diagnosis and CAR T-cell infusion, performance status (a measure of how well a patient can carry out daily activities), and other patient- and treatment-related variables. They also collected data on safety, efficacy, survival, frailty, geriatric attributes, and whether patients would have met eligibility criteria for the KarMMa clinical trial.\u003c\/p\u003e\n\n\u003cp\u003eTo evaluate frailty status at the time of leukapheresis, the researchers used a simplified Facon frailty scale based on three factors: age, Charlson Comorbidity Index (CCI, a measure of comorbidity burden), and Eastern Cooperative Oncology Group (ECOG) performance status. All geriatric attributes and KarMMa eligibility information were captured at the time of leukapheresis.\u003c\/p\u003e\n\n\u003cp\u003eA total of 156 patients were infused with ide-cel between May 12, 2021, and August 31, 2022. Among 8 patients who underwent leukapheresis but did not receive the ide-cel infusion, 2 had a manufacturing failure and 6 died before infusion (5 because of progressive disease and 1 because of sepsis). Of the 75 older patients (aged ≥65 years), 36 were aged 70 years or older.\u003c\/p\u003e\n\n\u003cp\u003eThe American Society for Transplantation and Cellular Therapy criteria were used to grade cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). The Common Terminology Criteria for Adverse Events, version 5.0, was used to grade all hematologic (blood-related) toxicities. The International Myeloma Working Group criteria were used by each institution to grade response to therapy. The study received institutional review board or ethics committee approval at each participating institution.\u003c\/p\u003e\n\n\u003ch2 id=\"findings\"\u003eKey Findings: What the Researchers Discovered\u003c\/h2\u003e\n\n\u003cp\u003eThe study divided patients into two groups for comparison: younger patients (aged \u0026lt;65 years, n=81) and older patients (aged ≥65 years, n=75). The median age at the time of CAR T-cell infusion was 58 years (range 42-64) for younger patients and 69 years (range 65-83) for older patients (P\u0026lt;.001).\u003c\/p\u003e\n\n\u003cp\u003eBaseline characteristics were largely similar between the two age groups. A poor ECOG performance status of ≥2 (meaning the patient was at least partially bedridden) at the time of lymphodepletion chemotherapy was 13% for both age groups. The older patient group included:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e61% male patients\u003c\/li\u003e\n  \u003cli\u003e28% non-White patients\u003c\/li\u003e\n  \u003cli\u003e60% with immunoglobulin G (IgG) subtype disease\u003c\/li\u003e\n  \u003cli\u003e41% with extramedullary disease (cancer outside the bone marrow)\u003c\/li\u003e\n  \u003cli\u003e23% with high marrow burden (≥50% plasma cells in the pre-CAR T-cell bone marrow biopsy)\u003c\/li\u003e\n  \u003cli\u003e25% with Revised International Staging System (R-ISS) stage III disease\u003c\/li\u003e\n  \u003cli\u003e39% with any high-risk cytogenetics (genetic abnormalities including del17p, t[4;14], and t[14;16])\u003c\/li\u003e\n  \u003cli\u003e71% received bridging therapy (treatment given while waiting for CAR T-cell manufacturing)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe median number of prior lines of therapy was 6 for both groups, and the median time from diagnosis to CAR T-cell infusion was 7 years. However, younger patients were more likely to have triple-class refractory disease (disease that does not respond to three major classes of myeloma drugs) at 95% compared to 84% in older patients (P\u0026lt;.05).\u003c\/p\u003e\n\n\u003cp\u003eFor the older patient group specifically, the key results were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBest overall response rate (ORR): 86.7%\u003c\/strong\u003e — comparable to the pivotal KarMMa study results (73%)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMedian progression-free survival (PFS): 9.1 months\u003c\/strong\u003e (time before the cancer progressed)\u003c\/li\u003e\n  \u003cli\u003e\u003cstrong\u003eMedian overall survival (OS): 26.5 months\u003c\/strong\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003cstrong\u003eGrade ≥3 cytokine-release syndrome: 1%\u003c\/strong\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003cstrong\u003eGrade ≥3 immune effector cell–associated neurotoxicity syndrome: 4%\u003c\/strong\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003ePerhaps most importantly, the safety and efficacy of ide-cel therapy were similar in younger and older patients. Frailty and geriatric characteristics such as polypharmacy (taking multiple medications), comorbidities, and organ dysfunction in older patients did not lead to inferior overall outcomes.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSafety Profile: Side Effects in Older vs Younger Patients\u003c\/h2\u003e\n\n\u003cp\u003eCAR T-cell therapy is known to cause distinct side effects, most notably cytokine-release syndrome (a systemic inflammatory response that can cause fever, low blood pressure, and breathing difficulties) and immune effector cell–associated neurotoxicity syndrome (neurological symptoms including confusion, difficulty speaking, and seizures).\u003c\/p\u003e\n\n\u003cp\u003eIn terms of CRS, the overall incidence of any grade was 81.5% for younger patients and 88.0% for older patients (P=.53, not statistically significant). Severe (grade ≥3) CRS was rare, observed in only 2 younger patients (2.4%) and 1 older patient (1.2%). The median time to maximum grade CRS was 1 day for both groups.\u003c\/p\u003e\n\n\u003cp\u003eFor ICANS, the overall incidence of any grade was not significantly different by age (P=.14), although it was slightly higher for older patients (25.3%) than for younger patients (13.6%). Severe (grade ≥3) ICANS was observed in 4 younger patients (4.9%) and 3 older patients (4.0%). The median time to maximum grade ICANS was shorter at 1.5 days for older patients compared with 3 days in younger patients — a difference that reached borderline significance (P\u0026lt;.1).\u003c\/p\u003e\n\n\u003cp\u003eLow blood counts (cytopenias) are another common side effect of CAR T-cell therapy. The prevalence of severe (grade ≥3) neutropenia (low white blood cell count), anemia (low red blood cell count), and thrombocytopenia (low platelet count) at day 30, day 60, and day 90 after infusion did not differ significantly between the two age groups.\u003c\/p\u003e\n\n\u003cp\u003eSupportive care requirements were also similar. During month 3 (days 61-90) after CAR T-cell therapy, the number of patients requiring growth factor support (medications to boost white blood cell production), blood transfusion, or platelet transfusion was comparable:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eGrowth factor support: 15.6% of younger vs 15.3% of older patients\u003c\/li\u003e\n  \u003cli\u003eBlood transfusion: 11.7% of younger vs 12.5% of older patients\u003c\/li\u003e\n  \u003cli\u003ePlatelet transfusion: 7.8% of younger vs 9.7% of older patients\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe rate of intravenous immunoglobulin (IVIG) use — a treatment to boost the immune system in patients with low antibody levels — was 27.2% in younger patients and 37.3% in older patients. The median duration of hospitalization was 9 days for both age groups. The number of patients requiring intensive care unit (ICU) stays was 7.4% (n=6) for younger patients and 4.0% (n=3) for older patients.\u003c\/p\u003e\n\n\u003cp\u003eA total of 11 types of viral infections were reported in the study population. The total number of patients with viral infections was numerically higher in the older group (24.0%, n=18) than in the younger group (17.2%, n=14), though this difference was not statistically significant.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eIn plain terms:\u003c\/strong\u003e Older patients did not experience more severe side effects from ide-cel therapy than younger patients. The side-effect profile was remarkably similar, which is reassuring for older patients considering this treatment.\u003c\/p\u003e\n\n\u003ch2 id=\"response\"\u003eTreatment Response: How Well Did Ide-cel Work?\u003c\/h2\u003e\n\n\u003cp\u003eAll 156 patients infused with ide-cel were evaluable for treatment response. The rates of best overall response (which includes complete response, very good partial response, and partial response) were similar between the age groups:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eBest ORR: 84.0% in patients under 65 years vs 86.7% in patients aged 65 years and older\u003c\/li\u003e\n  \u003cli\u003eComplete response (CR) or better: 54.3% in younger patients vs 56.0% in older patients\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThere was no significant difference in best ORR between the age groups (P=.92). This is particularly striking because older patients in this study had higher rates of frailty and comorbidities, yet still achieved comparable responses.\u003c\/p\u003e\n\n\u003cp\u003eThe response rates in this real-world older patient population (86.7%) actually exceeded the response rate reported in the pivotal KarMMa clinical trial (73%). This challenges the assumption that real-world patients — who are typically less healthy than clinical trial participants — would respond less well to treatment.\u003c\/p\u003e\n\n\u003ch2 id=\"survival\"\u003eSurvival Outcomes: Progression-Free and Overall Survival\u003c\/h2\u003e\n\n\u003cp\u003eProgression-free survival (PFS) is the length of time during and after treatment that a patient lives without the cancer getting worse. Overall survival (OS) is the length of time from treatment until death from any cause.\u003c\/p\u003e\n\n\u003cp\u003eThere was no significant difference in PFS by age category (P=.39). The median PFS was 7.4 months for younger patients compared with 9.1 months for older patients. In fact, older patients had a numerically (though not statistically) longer PFS than younger patients.\u003c\/p\u003e\n\n\u003cp\u003eSeveral factors were found to be significantly associated with the risk of progressive disease in univariate analysis (which looks at each factor individually):\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eHigh-risk cytogenetics (genetic abnormalities): hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.0-3.2; P=.044\u003c\/li\u003e\n  \u003cli\u003eTriple-refractory status (refractory to ≥1 immunomodulatory drug, ≥1 proteasome inhibitor, and ≥1 anti-CD38 monoclonal antibody): HR 0.4; 95% CI 0.2-0.8; P=.010\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eIn multivariable analysis (which accounts for multiple factors simultaneously) for older patients:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003ePrior BCMA-directed therapy (treatment targeting the B-cell maturation antigen): HR 5.1; 95% CI 1.1-22.7; P=.034 — meaning these patients had 5 times the risk of disease progression\u003c\/li\u003e\n  \u003cli\u003eTriple-refractory status: HR 0.2; 95% CI 0.08-0.46; P\u0026lt;.001 — meaning triple-refractory status was actually associated with a lower risk of progression in the multivariable model\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eOverall survival was also not different between the age groups (P=.62). The 12-month overall survival rates were 76.5% for younger patients and 68% for older patients. For older patients specifically:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eECOG performance status score of ≥2 at lymphodepletion chemotherapy (HR 2.7; 95% CI 1.1-6.3; P=.026) was significantly associated with inferior OS in univariate analysis\u003c\/li\u003e\n  \u003cli\u003eTriple-refractory status (HR 0.3; 95% CI 0.1-0.8; P=.023) was significantly associated with overall survival in multivariable analysis\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003eIn plain terms:\u003c\/strong\u003e Being older did not put patients at a disadvantage for survival outcomes after ide-cel therapy. Other factors — such as high-risk genetics, prior BCMA-directed therapy, and poor performance status — were more important predictors of outcomes than chronological age.\u003c\/p\u003e\n\n\u003ch3\u003eCauses of Death\u003c\/h3\u003e\n\n\u003cp\u003eAt the time of data cutoff, 73 (46.7%) of all patients had died, including 39 (53.4%) younger patients and 34 (46.5%) older patients. Most deaths (n=55; 75.3%) were myeloma-related due to progressive disease, including 31 (79.5%) younger and 24 (70.6%) older patients.\u003c\/p\u003e\n\n\u003cp\u003eThe number of non-relapse mortality events was 18 (24.7%), including 8 (20.5%) younger and 10 (29.4%) older patients. The causes of non-relapse mortality varied:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eCardiac causes contributed to the deaths of 3 older patients (8.8%): 1 due to cardiac failure, 1 due to cardiac arrest, and 1 due to cardiac amyloidosis\u003c\/li\u003e\n  \u003cli\u003e10 patients (5 in each group) died because of infections, including 4 related to COVID-19 (2 in each group), 3 related to unknown infections in the older group, and 3 related to bacterial infection in the younger group\u003c\/li\u003e\n  \u003cli\u003e2 younger patients died because of treatment toxicities: 1 related to grade 5 CRS and 1 related to unspecified neurotoxicity\u003c\/li\u003e\n  \u003cli\u003e1 older patient died because of Lewy-body dementia (an unrelated neurological condition)\u003c\/li\u003e\n  \u003cli\u003e2 patients (1 in each group) died of unspecified causes\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"frailty\"\u003eFrailty and Geriatric Characteristics\u003c\/h2\u003e\n\n\u003cp\u003eFrailty is a geriatric syndrome characterized by decreased strength, endurance, and physiologic function that increases an individual's vulnerability to poor health outcomes. It is a crucial consideration in treating older cancer patients.\u003c\/p\u003e\n\n\u003cp\u003eA total of 137 of 156 patients were evaluable for frailty. As shown in the study:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e46.5% of younger patients (n=33) were identified as frail\u003c\/li\u003e\n  \u003cli\u003e66.7% of older patients (n=44) were identified as frail (P=.017)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eNineteen patients were not included in the frailty analysis because of missing data for either ECOG performance status or Charlson Comorbidity Index.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers also analyzed a set of selected geriatric characteristics to understand their prevalence in both age groups:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePolypharmacy (taking ≥5 medications):\u003c\/strong\u003e 97.3% of older patients vs 87.7% of younger patients (P\u0026lt;.05)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eExcessive polypharmacy (≥10 medications):\u003c\/strong\u003e 70.7% of older patients vs numerically higher but not statistically significant\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eComorbidities (≥4 additional health conditions):\u003c\/strong\u003e 69.3% of older patients vs 53.1% of younger patients (P\u0026lt;.05)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePolyneuropathy (nerve damage causing numbness, tingling, or pain):\u003c\/strong\u003e 74.7% of older patients vs numerically higher but not statistically significant\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eFalls:\u003c\/strong\u003e 26.7% of older patients vs numerically higher but not statistically significant\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOrgan dysfunction:\u003c\/strong\u003e 34.7% of older patients vs 17.3% of younger patients (P\u0026lt;.05)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe study also reanalyzed all 156 patients using a different age cutoff (aged \u0026lt;70 vs aged ≥70). A notable discrepancy was observed in frailty prevalence: 46.7% of patients under 70 were frail compared with 87.5% of patients aged 70 years and older (P\u0026lt;.001). Despite this much higher frailty burden in the oldest patients, treatment outcomes remained similar:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eORR: 84.2% for patients under 70 vs 88.9% for patients aged 70 and older\u003c\/li\u003e\n  \u003cli\u003eCR or better: 54.2% vs 58.3%\u003c\/li\u003e\n  \u003cli\u003eMedian PFS: 7.5 months vs 9.8 months\u003c\/li\u003e\n  \u003cli\u003eMedian OS: 24.2 months vs greater than 28 months\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThese findings are remarkable. Even the oldest and frailest patients — nearly 9 out of 10 of whom were classified as frail — achieved excellent responses to ide-cel therapy with the same side-effect profile as younger patients.\u003c\/p\u003e\n\n\u003ch2 id=\"comorbidities\"\u003eComorbidities and Clinical Trial Eligibility\u003c\/h2\u003e\n\n\u003cp\u003eBeyond assessing whether patients had 4 or more comorbidities (a marker used in frailty assessment), the researchers also analyzed specific individual comorbidities. The prevalence of having at least one comorbidity was 94.0% in younger patients and 97.5% in older patients. A total of 87 comorbidities were recorded in the younger group versus 102 in the older group.\u003c\/p\u003e\n\n\u003cp\u003eThe most frequent comorbidities present in at least 10% of patients in each group included:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eNeuropathy (nerve damage)\u003c\/li\u003e\n  \u003cli\u003eHypertension (high blood pressure)\u003c\/li\u003e\n  \u003cli\u003ePain\u003c\/li\u003e\n  \u003cli\u003eDiabetes\u003c\/li\u003e\n  \u003cli\u003eHyperlipidemia (high cholesterol)\u003c\/li\u003e\n  \u003cli\u003eImmunodeficiency (weakened immune system)\u003c\/li\u003e\n  \u003cli\u003eRenal dysfunction (kidney problems)\u003c\/li\u003e\n  \u003cli\u003eGastroesophageal reflux disease (GERD, chronic acid reflux)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThese conditions were common across both age categories. However, the prevalence of all of these comorbidities — except GERD — was higher in older patients. Anxiety, depression, and arthritis were more frequent in younger patients, while anemia, obstructive sleep apnea, and hypothyroidism (underactive thyroid) were observed more commonly in older patients.\u003c\/p\u003e\n\n\u003cp\u003eRenal impairment (kidney dysfunction) was particularly notable. A total of 18 (11.5%) patients in the study had renal impairment (creatinine clearance of \u0026lt;50 mL\/min, a measure of kidney function), including 7 (4.5%) patients with severe renal impairment (creatinine clearance of \u0026lt;30 mL\/min). The majority of patients with renal impairment and severe renal impairment were older: 17 older patients (22.7%) had renal impairment, and 6 (8.0%) had severe renal impairment.\u003c\/p\u003e\n\n\u003cp\u003eAmong cardiac conditions:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eCongestive heart failure was reported in 1 (1.2%) younger patient and 5 (6.6%) older patients\u003c\/li\u003e\n  \u003cli\u003eCardiac arrhythmias (irregular heartbeats) were reported in 7 (8.6%) younger patients and 12 (16%) older patients\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe researchers also assessed whether patients would have met the eligibility criteria for the KarMMa clinical trial — the pivotal study that led to FDA approval of ide-cel. This was important because clinical trial eligibility criteria are often stricter than real-world practice, and many older patients who receive treatment in the clinic would have been excluded from the trial.\u003c\/p\u003e\n\n\u003cp\u003eThe results were striking:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e65.4% of younger patients did NOT meet eligibility criteria for KarMMa trial participation\u003c\/li\u003e\n  \u003cli\u003e77.3% of older patients did NOT meet eligibility criteria\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eExclusion because of cardiac dysfunction and renal insufficiency was more prevalent in older patients, while laboratory abnormalities were more frequent exclusion events in younger patients. This finding underscores the fact that the original KarMMa trial population was highly selective and not fully representative of patients treated in the real world — especially older patients.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eClinical Implications: What This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThis study provides strong evidence that chronological age alone should not be a barrier to receiving CAR T-cell therapy with ide-cel. In contrast to the inferior outcomes often observed in older patients compared with younger counterparts receiving other anti-myeloma therapies, ide-cel demonstrates comparable efficacy and safety profiles across age groups.\u003c\/p\u003e\n\n\u003cp\u003eThe key takeaway for patients is that even with high rates of frailty, polypharmacy, comorbidities, and organ dysfunction, older patients achieved:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eAn 86.7% overall response rate\u003c\/li\u003e\n  \u003cli\u003eA 56% complete response rate or better\u003c\/li\u003e\n  \u003cli\u003eA median progression-free survival of 9.1 months\u003c\/li\u003e\n  \u003cli\u003eA median overall survival of 26.5 months (over 2 years)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003ePerhaps most importantly, 66.7% of the older patients in this study were classified as frail, and 77.3% would not have qualified for the KarMMa clinical trial. Yet they still achieved outcomes that were as good as — if not better than — the results seen in the pivotal trial. This suggests that strict clinical trial eligibility criteria may be unnecessarily excluding patients who could genuinely benefit from this therapy.\u003c\/p\u003e\n\n\u003cp\u003eThe study also highlights several practical points for clinicians:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003eAge alone should not determine eligibility for ide-cel therapy\u003c\/li\u003e\n  \u003cli\u003ePrior BCMA-directed therapy was associated with a 5-fold higher risk of disease progression in older patients (HR 5.1; 95% CI 1.1-22.7; P=.034), suggesting that the timing of CAR T-cell therapy relative to other treatments may matter\u003c\/li\u003e\n  \u003cli\u003ePoor ECOG performance status (≥2) at lymphodepletion was associated with inferior overall survival in older patients (HR 2.7; 95% CI 1.1-6.3; P=.026), highlighting the importance of assessing functional status\u003c\/li\u003e\n  \u003cli\u003eCardiac conditions, especially arrhythmias and congestive heart failure, were common in older patients and contributed to some non-relapse deaths — cardiac monitoring is essential\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eThis is, to the best of the authors' knowledge, the first multicenter study that evaluated safety and efficacy along with frailty and geriatric characteristics in real-world older patients with multiple myeloma who received ide-cel. It fills an important knowledge gap, since older patients are often underrepresented in clinical trials despite being the majority of the myeloma patient population.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations: What This Study Couldn't Prove\u003c\/h2\u003e\n\n\u003cp\u003eAs with all research, this study has limitations that should be considered when interpreting the results:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRetrospective design:\u003c\/strong\u003e Because this was a retrospective study (looking back at data already collected), it cannot establish cause-and-effect relationships with the same confidence as a prospective, randomized controlled trial.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSelection bias:\u003c\/strong\u003e The patients in this study were selected to receive ide-cel based on their physicians' judgment, creating a selection bias. The outcomes may differ for patients who were considered for ide-cel but did not receive it (indeed, 8 patients did not make it to infusion — 6 died before infusion and 2 had manufacturing failures).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMissing confirmatory testing:\u003c\/strong\u003e Confirmation of complete response for patients with extramedullary disease (cancer outside the bone marrow) was not mandated because of the retrospective study design, which could affect response rate accuracy.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMissing data:\u003c\/strong\u003e Frailty data were missing for 19 patients, and some other data elements were also incomplete (e.g., cytogenetic status was unknown for some patients).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSample size:\u003c\/strong\u003e While 156 patients is a reasonably large real-world cohort, subgroup analyses (such as the analysis of patients aged ≥70) involved smaller numbers of patients, making statistical comparisons less robust.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNo control group:\u003c\/strong\u003e The study did not compare ide-cel to other treatments in older patients, so it cannot determine whether ide-cel is superior to other options in this population.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMedication details:\u003c\/strong\u003e The study captured data on polypharmacy (number of medications) but did not analyze specific medication interactions, which may be relevant in older patients.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNon-relapse mortality:\u003c\/strong\u003e The rates of non-relapse mortality from cardiac causes and infections in older patients (29.4%) highlight that comorbidities can still contribute to deaths even when the myeloma itself is controlled.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations: Advice for Patients and Caregivers\u003c\/h2\u003e\n\n\u003cp\u003eBased on this study's findings, here are practical recommendations for older patients with multiple myeloma who may be considering CAR T-cell therapy, along with advice for their caregivers and families:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDon't let age alone discourage you:\u003c\/strong\u003e If your doctor recommends CAR T-cell therapy, age by itself should not be a reason to decline or be denied treatment. This study shows that patients aged 65 and older — including those aged 80 and above — can achieve excellent outcomes.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss your frailty and functional status openly:\u003c\/strong\u003e Your doctor will likely assess your frailty, comorbidities, and ability to perform daily activities. Be honest about your physical limitations so your care team can plan appropriate support.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about cardiac monitoring:\u003c\/strong\u003e Heart conditions were relatively common in older patients in this study (16% had arrhythmias, 6.6% had congestive heart failure), and cardiac issues contributed to some deaths. Ask your care team about cardiac evaluations before, during, and after CAR T-cell therapy.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eExpect a CAR T-cell \"time out\":\u003c\/strong\u003e The median hospitalization stay in this study was 9 days, with about 4% of older patients requiring ICU care. Plan for this period and ensure you have a caregiver available.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBe aware of infection risk:\u003c\/strong\u003e One-quarter (24%) of older patients experienced viral infections. Ask your doctor about preventive measures, including vaccination (especially COVID-19) and immunoglobulin infusions (IVIG) to boost your immune system.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKnow that clinical trial eligibility differs from real-world success:\u003c\/strong\u003e The majority of older patients in this study (77.3%) would not have qualified for the pivotal KarMMa clinical trial, yet they still achieved excellent outcomes. Don't be discouraged if you don't meet clinical trial criteria — real-world treatment can still work well.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMonitor blood counts after infusion:\u003c\/strong\u003e Low blood counts are common and may require growth factor support, blood transfusions, or platelet transfusions for up to 90 days or longer. These supportive measures were used frequently in both age groups.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss the timing of therapy:\u003c\/strong\u003e The study found that prior BCMA-directed therapy was associated with a higher risk of disease progression in older patients. Discuss with your doctor the optimal timing of CAR T-cell therapy in your treatment sequence.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eConsider performance status carefully:\u003c\/strong\u003e A poor ECOG performance status (≥2) before lymphodepletion was associated with shorter overall survival. Work with your care team to optimize your physical function before starting treatment if possible.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKeep perspective:\u003c\/strong\u003e The median overall survival for older patients was 26.5 months (over 2 years) even in a heavily pretreated population (median of 6 prior lines of therapy). For many patients, this represents a substantial extension of life with meaningful quality time.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eI'm 72 and was told I'm too old for CAR T-cell therapy. Is that true?\u003c\/h3\u003e\n\u003cp\u003eIn a real-world study of 156 patients, those aged 65 and older who received ide-cel had an 86.7% response rate and side effects similar to younger patients, despite more frailty and other conditions. The researchers concluded that age alone should not disqualify older patients from this therapy. Discuss your individual situation with your care team.\u003c\/p\u003e\n\u003ch3\u003eWhat can I do to prepare for CAR T-cell therapy?\u003c\/h3\u003e\n\u003cp\u003eThe study authors suggest discussing your frailty and functional status openly, asking about cardiac monitoring before and after treatment, and planning for a hospital stay of about 9 days with a caregiver. Ask about vaccinations and immunoglobulin infusions to reduce infection risk. Work with your care team to optimize your physical function before treatment if possible.\u003c\/p\u003e\n\u003ch3\u003eI have multiple myeloma and I'm over 65 — should I get a second opinion before starting CAR T-cell therapy with ide-cel?\u003c\/h3\u003e\n\u003cp\u003eAge alone should not disqualify you from ide-cel. In 156 real-world patients, those aged 65 and older had an 86.7% overall response rate, median overall survival of 26.5 months, and side effects similar to younger patients, even though 66.7% were frail and 77.3% would not have qualified for the pivotal trial. A second opinion can help confirm whether ide-cel is appropriate given your frailty, heart health, kidney function, prior BCMA-directed therapy, and performance status. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003eThis patient-friendly article is based on the following peer-reviewed research:\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal Article Title:\u003c\/strong\u003e Clinical outcomes after idecabtagene vicleucel in older patients with multiple myeloma- a multicenter real-world experience\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Nilesh M. Kalariya, Michelle A.T. Hildebrandt, Doris K. Hansen, Surbhi Sidana, Jack Khouri, Christopher J. Ferreri, William N. Doyle, Omar Castaneda-Puglianini, Ciara L. Freeman, Vanna Hovanky, Hitomi Hosoya, Leyla O. Shune, and Krina K. Patel\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eJournal:\u003c\/strong\u003e Blood Advances, Volume 8, Number 17, September 10, 2024, pages 4679-4684\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication Details:\u003c\/strong\u003e Submitted May 1, 2024; accepted July 12, 2024; prepublished online on Blood Advances First Edition July 23, 2024. DOI: https:\/\/doi.org\/10.1182\/bloodadvances.2024013540\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eParticipating Institutions:\u003c\/strong\u003e The University of Texas MD Anderson Cancer Center (Houston, TX); H. Lee Moffitt Cancer Center and Research Institute (Tampa, FL); Stanford University School of Medicine (Stanford, CA); Cleveland Clinic Taussig Cancer Center (Cleveland, OH); Atrium Health\/Wake Forest University School of Medicine, Levine Cancer Institute (Charlotte, NC); and The University of Kansas Medical Center (Kansas City, KS).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\/Disclosures:\u003c\/strong\u003e The study was a collaborative real-world analysis. N.M.K. and M.A.T.H. are joint first authors and contributed equally. L.O.S. and K.K.P. are joint senior authors.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eNote:\u003c\/strong\u003e This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace individualized medical advice. Always consult with your oncology care team about your specific treatment plan and options.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47699375358108,"sku":null,"price":0.0,"currency_code":"KRW","in_stock":true}],"url":"https:\/\/diagnosticdetectives.kr\/products\/car-t-cell-therapy-ide-cel-works-well-in-older-adults-with-multiple-myeloma-a-multicenter-real-world-study","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}