CAR T-Cell Therapy Proves Safe and Effective for Octogenarians with B-Cell Lymphoma
核心洞察
A multicenter retrospective study of 88 patients aged 80 and older demonstrated that CAR T-cell therapy is feasible and effective for treating relapsed/refractory B-cell lymphoma in octogenarians.
Over 70% of evaluable patients achieved complete response, with one-year progression-free survival rates of 57.6% for DLBCL/tFL patients and 45% for mantle cell lymphoma (搜索) patients.
Toxicity profiles were comparable to younger patients, with 77.3% experiencing cytokine release syndrome (搜索) and 58% developing immune effector cell-associated neurotoxicity syndrome (搜索).
A groundbreaking multicenter study has demonstrated that CAR T-cell therapy can be safely and effectively administered to patients aged 80 and older with relapsed/refractory B-cell lymphoma, challenging traditional age-based exclusion criteria for this potentially curative treatment. The research, conducted across 16 cancer centers, provides crucial evidence for treating octogenarians who represent approximately one-third of patients diagnosed with diffuse large B-cell lymphoma (搜索) and follicular lymphoma (搜索).
Study Design and Patient Population
Researchers reviewed patient records from 88 patients aged 80 and older (median age 82 years) who received CD19 (搜索)-directed CAR T-cell therapy between January 2018 and December 2023. The patient population included 68.2% with diffuse large B-cell lymphoma (搜索) (DLBCL), 18.2% with transformed follicular lymphoma (搜索) (tFL), and 10.2% with mantle cell lymphoma (搜索) (MCL). Twenty-four percent of patients had double-hit lymphoma (搜索).
Nearly half of the patients (46.6%) received axicabtagene ciloleucel (axi-cel), with the remaining patients receiving brexucabtagene (搜索), lisocabtagene maraleucel (liso-cel), or tisagenlecleucel (CTL019).
Efficacy Outcomes
The study revealed encouraging efficacy results comparable to those observed in younger patient populations. More than 70% of evaluable patients achieved a complete response, while 17.9% achieved a partial response. The one-year progression-free survival rate was 57.6% for patients with DLBCL or tFL, and 45% for patients with MCL. The one-year overall survival rate reached 61.2% for patients with DLBCL or transformed follicular lymphoma (搜索).
"The study demonstrated that CAR T-cell therapy is feasible in patients 80 and older," stated Dr. Deepa Jagadeesh, a staff physician in the Hematology and Medical Oncology department at Cleveland Clinic Cancer Institute (搜索). "The one-year progression-free survival was close to 50%, which is very encouraging. This is a reminder to physicians not to use age as a single exclusion criterion."
Safety Profile and Toxicity Management
The toxicity profile in octogenarians proved comparable to that observed in younger patients. Cytokine release syndrome (搜索) (CRS) of any grade occurred in 77.3% of patients, with only 7.4% experiencing grades 3-4 severity and a median symptom duration of three days. Immune effector cell-associated neurotoxicity syndrome (搜索) (ICANS) developed in 58% of patients, with 31.4% experiencing grade 3-4 severity and a median symptom duration of six days.
The majority of patients with CRS received tocilizumab, while those experiencing ICANS received dexamethasone. "It's reassuring to see that more physicians are aware of the potential toxicities and are being proactive in treating them," noted Dr. Jagadeesh.
Nearly a quarter of patients required readmission to the hospital within the first 100 days after CAR T-cell therapy administration. Reasons for readmission included recurrence of CRS or ICANS, failure to thrive, atrial fibrillation, or infection. The non-relapse mortality rate at one year was 11.6%, with a relapse rate of 40.8%.
Clinical Implications and Recommendations
The study highlighted several important clinical considerations for treating elderly patients with CAR T-cell therapy. The researchers emphasized the importance of incorporating frailty assessment tools to identify appropriate octogenarian candidates for treatment.
Timing emerged as a crucial factor, with swift initiation of second- or third-line therapy being essential for many patients. "It's important for community physicians to reach out to refer patients for CAR T-cell therapy evaluation early," Dr. Jagadeesh emphasized. "Earlier referral would allow CAR T-cell centers to evaluate if the patient is eligible for such therapy, as it offers the potential for a cure."
The study also underscored the critical role of multidisciplinary care for patients with comorbidities. While comorbidities don't necessarily disqualify patients from CAR T-cell therapy, they require additional supportive measures. For instance, patients with heart conditions should have cardiology consultation upfront, as CRS treatment with fluids can exacerbate preexisting heart failure. Similarly, patients with diabetes may need endocrinology involvement to manage blood sugar levels during steroid treatment for ICANS.
Addressing Treatment Gaps
The research highlighted ongoing gaps in access to CAR T-cell therapy for elderly patients. "In most cases, older patients were excluded from CAR T-cell therapy trials due to medical comorbidities or suboptimal functional status," Dr. Jagadeesh explained. "We wanted to understand how these patients fared on this emerging treatment."
Currently, older patients with refractory disease are often prescribed chemotherapy, polatuzumab vedotin in the second-line setting, or bispecific antibodies in the third-line setting. However, none of these options are curative, making CAR T-cell therapy the only potentially curative option for refractory B-cell lymphoma.
As CAR T-cell therapy becomes available at more locations and increasingly used on an outpatient basis, barriers to access may be reduced. "There has been an explosion of new treatments for diffuse large B-cell lymphoma (搜索)," Dr. Jagadeesh noted. "We need to be considering each of these at the correct time, and ensure all patients who are eligible have access to appropriate treatment."
The researchers acknowledged the need for larger databases and longer-term outcomes to build on these findings, as well as better understanding of barriers patients face in receiving CAR T-cell therapy.