Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM) with Renal Impairment: Real World Experience

Sidana, Surbhi; Peres, Lauren C.; Hashmi, Hamza; Hosoya, Hitomi; Ferreri, Christopher J.; Atrash, Shebli; Khouri, Jack; Voorhees, Peter M.; Dima, Danai; Simmons, Gary; Kalariya, Nilesh; Hovanky, Vanna; Bharadwaj, Sushma; Arai, Sally; Miklos, David B.; Wagner, Charlotte; Davis, James A.; Sborov, Douglas W.; Nishihori, Taiga; Alsina, Melissa; Locke, Frederick L.; Gonzalez, Rebecca; Kocoglu, Mehmet H.; Sannareddy, Aishwarya; Afrough, Aimaz; McGuirk, Joseph P.; Shune, Leyla; Patel, Krina; Hansen, Doris K.

doi:10.1016/s2666-6367(23)00111-2

Cited by 5 publications

(4 citation statements)

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“…Exclusion of less than four previous lines showed similar results for the comparison of both cohorts (Data Supplement, Fig S13). Despite these limitations, outcome in our study was comparable with recently reported real-world results, 22 , 46 with the important addition of comparability between regions and products. Future studies should prospectively validate the prediction model.…”

Section: Discussionsupporting

confidence: 88%

“…Efficacy results in our study were in line with previous retrospective reports and prospective trial populations. 4,22,23 In addition, we described the difference in patient and treatment characteristics between Europe and the United States (such as the number of previous lines of therapy, time to CAR-T infusion, performance status) and showed similar response rates and PFS/OS results in both the European and US cohorts. Furthermore, it has been widely acknowledged that the expansion of CAR-T across indications and treatment lines might impose a significant burden to health care systems and might limit its broad access for all patients 24 because of its complex production and subsequent high costs.…”

Section: Discussionmentioning

confidence: 94%

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Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

Gagelmann,

Dima,

Merz

et al. 2024

JCO

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PURPOSE Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T. PATIENTS AND METHODS This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti–B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133). Independent predictors of relapse/progression built a simple prediction model (Myeloma CAR-T Relapse [MyCARe] model) in the training cohort (Europe), which was externally validated (US cohort) and tested within patient- and treatment-specific subgroups. RESULTS The overall response rate was 87% and comparable between both cohorts, and complete responses were seen in 48% (Europe) and 49% (the United States). The median time to relapse was 5 months, and early relapse <5 months from infusion showed poor survival across cohorts, with the 12-month overall survival of 30% (Europe) and 14% (the United States). The presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. Each factor received one point, forming the three-tiered MyCARe model: scores 0-1 (low risk), scores 2-3 (intermediate risk), and a score of 4 (high risk). The MyCARe model was significantly associated with distinct 5-month incidence of relapse/progression ( P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. The model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups. CONCLUSION Outcomes of patients with RRMM after CAR-T are comparable between Europe and the United States. The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 94%

Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

Gagelmann,

Dima,

Merz

et al. 2024

JCO

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“…A recent study by Sidana et al. compared outcomes of patients who received SOC ide‐cel with or without renal impairment and found that most safety aspects including CRS, neurotoxicity and cytopenias, by 3 months following infusion were similar between the two groups 11 . Importantly, renal function did not worsen after CAR T in patients with pre‐existing renal impairment 11 …”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of idecabtagene vicleucel in patients with relapsed–refractory multiple myeloma not meeting the KarMMa‐1 trial eligibility criteria: A real‐world multicentre study

Dima,

Rashid,

Davis

et al. 2024

Br J Haematol

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SummaryIde‐cel received approval for relapsed–refractory multiple myeloma based on the results of the KarMMa‐1 trial. However, patients with significant comorbidities, aggressive disease and prior B‐cell maturation antigen‐directed therapy (BCMA‐DT) were excluded. This retrospective study evaluated real‐world outcomes of patients who did not meet the KarMMa‐1 eligibility criteria and were treated with standard of care (SOC) ide‐cel. A total of 69 patients from three US centres who did not meet the KarMMa‐1 criteria underwent ide‐cel infusion. The main reasons for trial ineligibility included baseline grade 3–4 cytopenia (39%), prior BCMA‐DT (26%), renal impairment (19%) and Eastern Cooperative Oncology Group performance status ≥2 (14.5%). Cytokine‐release syndrome occurred in 81% vs. 84%, and immune effector cell‐associated neurotoxicity syndrome occurred in 28% vs. 18% of SOC versus KarMMa‐1 patients, respectively. Early infection (≤8 weeks post‐infusion) and severe infection rates were 42% vs. 49% and 30% vs. 22% for the SOC versus KarMMa‐1 cohorts, respectively. Grade 3–4 cytopenias for SOC versus KarMMa‐1 cohorts were: neutropenia (87% vs. 89%), anaemia (51% vs. 60%) and thrombocytopenia (65% vs. 52%). Overall response rate was higher for the SOC cohort (93% vs. 73%), as was the complete response or better rate (48% vs. 33%). However, median progression‐free survival and overall survival were comparable between the two groups. Our findings support broadening the inclusion criteria of future trials evaluating ide‐cel.

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“…For patients requiring dialysis, regardless of the dose adjustment or route of administration, plasma-cell directed agents should be given after dialysis. A recent real-world multicenter experience of ide-cel in 28 patients with renal impairment reported comparable efficacy and safety to patients without renal dysfunction [ 209 , 210 ]. This is critical given that major CAR-T trials excluded patients with renal insufficiency.…”

Section: How To Approach Therapy Selectionmentioning

confidence: 99%

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Dima

Ullah

Mazzoni

et al. 2023

Cancers

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Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

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Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM) with Renal Impairment: Real World Experience

Cited by 5 publications

References 0 publications

Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

Efficacy and safety of idecabtagene vicleucel in patients with relapsed–refractory multiple myeloma not meeting the KarMMa‐1 trial eligibility criteria: A real‐world multicentre study

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

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