RESUMEN
Chimeric antigen receptor (CAR) T-cell therapy has shown promise in patients with late-line refractory multiple myeloma, with response rates ranging from 73 to 98%. To date, three products have been approved: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which are approved by the US Food and Drug Administration, the European Medicines Agency, Health Canada (ide-cel only), and Brazil ANVISA (cilta-cel only); and equecabtagene autoleucel (eque-cel), which was approved by the Chinese National Medical Products Administration. CAR T-cell therapy is different from previous anti-myeloma therapeutics with unique toxic effects that require distinct mitigation strategies. Thus, a panel of experts from the International Myeloma Working Group was assembled to provide guidance for clinical use of CAR T-cell therapy in myeloma. This consensus opinion is from experts in the field of haematopoietic cell transplantation, cell therapy, and multiple myeloma therapeutics.
Asunto(s)
Consenso , Inmunoterapia Adoptiva , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Mieloma Múltiple/terapia , Mieloma Múltiple/inmunología , Humanos , Inmunoterapia Adoptiva/efectos adversos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/uso terapéutico , Resultado del Tratamiento , Receptores de Antígenos de Linfocitos T/uso terapéutico , Receptores de Antígenos de Linfocitos T/inmunologíaRESUMEN
Multiple myeloma remains an incurable disease, despite the development of numerous drug classes and combinations that have contributed to improved overall survival. Immunotherapies directed against cancer cell-surface antigens, such as chimeric antigen receptor (CAR) T-cell therapy and T-cell-redirecting bispecific antibodies, have recently received regulatory approvals and shown unprecedented efficacy. However, these immunotherapies have unique mechanisms of action and toxicities that are different to previous treatments for myeloma, so experiences from clinical trials and early access programmes are essential for providing specific recommendations for management of patients, especially as these agents become available across many parts of the world. Here, we provide expert consensus clinical practice guidelines for the use of bispecific antibodies for the treatment of myeloma. The International Myeloma Working Group is also involved in the collection of prospective real-time data of patients treated with such immunotherapies, with the aim of learning continuously and adapting clinical practices to optimise the management of patients receiving immunotherapies.
Asunto(s)
Anticuerpos Biespecíficos , Consenso , Mieloma Múltiple , Linfocitos T , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Inmunoterapia/métodos , Inmunoterapia/normas , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVE: This study aimed to assess the cost-effectiveness of two regimens regarded as the standard of care for the treatment of newly diagnosed, transplant-ineligible multiple myeloma in Singapore: (1) daratumumab, lenalidomide, and dexamethasone and (2) bortezomib, lenalidomide, and dexamethasone. Additionally, it aimed to explore potential strategies to manage decision uncertainty and mitigate financial risk. METHODS: A cost-effectiveness analysis from the healthcare system perspective was conducted using a partitioned survival model to estimate lifetime costs and quality-adjusted life years (QALYs) associated with daratumumab-based treatment and the bortezomib-based regimen. The analysis used data from the MAIA and SWOG S0777 trials and incorporated local real-world data where available. Sensitivity analyses were performed to evaluate the robustness of the findings, and a risk analysis was conducted to analyze various payer strategies in terms of their payer strategy and uncertainty burden (P-SUB), which account for the decision uncertainty and the additional cost of choosing a suboptimal intervention. RESULTS: The incremental cost-effectiveness ratio (ICER) for daratumumab, lenalidomide, and dexamethasone (DRd) compared with bortezomib, lenalidomide, and dexamethasone (VRd) was US $90,364 per QALY gained. The results were sensitive to variations in survival for DRd, postprogression treatment costs, cost of hospice care, and hazard ratio for progression-free survival. The scenarios explored indicated that structural assumptions, such as the time horizon of the analysis, significantly influenced the results due to uncertainties arising from immature trial data and treatment efficacy over time. Among the various payer strategies compared, an upfront price discount for daratumumab emerged as the best approach with the lowest P-SUB at US $14,708. CONCLUSION: In conclusion, this study finds that daratumumab as a first-line treatment for myeloma exceeds the cost-effectiveness threshold considered in this evaluation. An upfront price reduction is the recommended strategy to manage uncertainties and mitigate financial risks. These findings highlight the importance of targeted payer strategies to address specific types and sources of uncertainty.
RESUMEN
Background: Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods: We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B-cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high-dose methotrexate (HD-MTX) containing chemotherapy regimens: MPV/Ara-C (HD-MTX, procarbazine, and vincristine, followed by cytarabine [Ara-C]) (n = 94, 50%), MATRix (HD-MTX, Ara-C, thiotepa, and rituximab) (n = 19, 10%), HD-MTX/Ara-C (n = 31, 16%), HD-MTX monotherapy (n = 35, 18%) and MBVP (HD-MTX, carmustine, teniposide, prednisolone) (n = 11, 6%). Results: Cumulative median HD-MTX and Ara-C doses were 17 g/m2 (range: 1-64 g/m2) and 12 g/m2 (0-32 g/m2) respectively. Using 14 g/m2 as the reference dose, the median HD-MTX relative dose intensity (HD-MTX-RDI) was 1.25 (0.27-4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD-MTX. At a median follow-up of 3.41 years (0.06-9.42), progression-free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara-C cohort (2-year PFS 74%, 2-year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara-C administration and HD-MTX-RDI > 0.75 were associated with longer PFS and OS. Conclusion: Sequential, response-adapted approaches can improve outcomes, even in older patients who are ineligible for a high-intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.
RESUMEN
AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical suspicion to detect unexplained manifestations in the appropriate clinical setting. Early detection and treatment are crucial as the degree of cardiac involvement emerges as a primary prognostic predictor of survival in a patient with AL amyloidosis. Following the diagnosis of AL amyloidosis with appropriate tissue biopsies, prompt treatment with a bortezomib, cyclophosphamide and dexamethasone-based first-line induction with or without daratumumab should be initiated. The goal of treatment is to achieve the best haematologic response possible, ideally with involved free light chain <20 mg/L, as it offers the best chance of organ function improvement. Treatment should be changed if patients do not achieve a partial response within 2 cycles of treatment or very good partial response after 4 cycles or after autologous stem cell transplant, as achievement of profound and prolonged clonal responses translates to better organ response and long-term outcomes. Early involvement of multidisciplinary subspecialists such as renal physicians, cardiologists, neurologists, and gastroenterologists for optimal maintenance and support of involved organs is recommended for optimal management of patients with AL amyloidosis.