Hematologic Malignancies: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective: Ciltacabtagene Autoleucel, a BCMA-Directed CAR T-Cell Therapy, in Relapsed/Refractory Multiple Myeloma: Updated Results From CARTITUDE-1, By JADPRO Staff

Donna Catamero

摘要

A single infusion of ciltacabtagene autoleucel (cilta-cel) yielded early, deep, and durable responses in heavily pre-treated patients with multiple myeloma (MM), with a manageable safety profile, according to results of the phase Ib/2 CARTITUDE-1 study presented at the 2021 ASCO Annual Meeting. Cilta-cel is a chimeric antigen receptor (CAR) T-cell therapy with two B-cell maturation antigen (BCMA)-targeting single-domain antibodies. Updated results were presented at the meeting in patients with a longer duration (median 12.4 months) of follow-up. The Advanced Practitioner Perspective: For the most part, multiple myeloma (MM) remains an incurable disease. Relapse is expected, and with each relapse it becomes increasingly challenging to manage patients, as responses tend not to be as deep and durable as in earlier lines of therapy. Cilta-cel is a unique CAR-T construct that has two BCMA bind domains, which can potentially lead to a higher affinity to binding to the BCMA antigen that is predominately found on MM cells. This phase Ib/2 clinical trial enrolled heavily pretreated patients with six median prior lines of therapy of which the majority of patients were triple-class refractory and refractory to their last line of treatment. We know historically that these patient have poor clinical outcomes. After a one-time infusion of cilta-cel with prior lymphodepleting chemotherapy, 98% of patients responded to therapy, and of those patients who did respond, an overwhelming majority achieved a stringent complete response (80%). The longer follow-up showed the progression-free survival at 18 months was 66%, demonstrating durable remissions. Benefits in response rate were seen across different patient populations (risk status, number of prior lines, and refractoriness). These are truly remarkable results for a patient population that historically does not achieve deep and durable remissions, especially in those patients with high-risk characteristics. From a safety perspective, with longer follow-up, there were no new safety signals seen. In the study, high-grade cytopenias were common. In practice, we can often manage cytopenias with supportive care (blood transfusions and growth factors). It is important as advanced practitioners that we frequently monitor patients immediately post CAR T-cell therapy to manage these adverse events. The majority of patients developed cytokine release syndrome (CRS). It was mostly limited to grade 1 and 2 with a median duration of 4 days. Low-grade CRS can be adequately managed with supportive care and administration of interleukin antagonists. Median time to onset of CRS was 7 days. Given the delayed onset of CRS, there is a potential of administering cilta-cel in the outpatient setting and thus avoiding prolonged hospital admissions. Neurotoxicity (NT) was seen in 20% of patients, half of which were a grade 3 or higher. A deeper dive in patients who had NT showed that patients who had two or more of the following risk factors were at higher risk for developing NT: high tumor burden, grade 2 or higher CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), or high CAR T-cell expansion and persistence. Mitigation strategies for patients who are at high risk for developing NT are to undergo an effective bridging therapy, implement early and aggressive management for CRS and ICANS, and monitoring handwriting as part of patient assessment. These mitigation strategies prevented or reduced NT in the extended cilta-cel clinical trial platform. Cilta-cel has demonstrated deep and durable remissions in a heavily pretreated patient population which in practice has limited treatment options and poor outcomes. This therapy could potentially offer patients prolonged disease-free intervals with a one-time dose of cilta-cel. The safety profile is manageable with frequent monitoring and early interventions with supportive care.

Hematologic Malignancies: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective: Ciltacabtagene Autoleucel, a BCMA-Directed CAR T-Cell Therapy, in Relapsed/Refractory Multiple Myeloma: Updated Results From CARTITUDE-1, By JADPRO Staff

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