Article type
Abstract
"BACKGROUND:
Chimeric-antigen receptor T-cell therapies (CART) are autologus reingeneered lymphocytes campable of targeting neoplasic lymphoid cells and achieve a high rate of response in refractory/relapsed (R/R) large B-cell lymphomas (LBL) and mantle cell lymphomas (MCL). The economic and safety drawbacks of CARTs impose a careful selection of patients, however, no randomized clinical trial compared CART to standard of care therapies (SOC), therefore direct evidence is missing. The Italian Ministry of Health invited the national scientific societies to develop GRADE-based clinical pratice guidelines (CPG) for the most relevant clinical issues. The CPG undergo a revision process and are finally published.
OBJECTIVES: The Italian Society of Hematology planned to develop GRADE-based recommendations for CARTs in the setting of R/R LBL and MCL. Satellite scientific societies (GITMO, SIDEM) were invited to contribute to the process.
METHODS: An Expert Panel (EP) of 7 hematologist, 1 transplant nurse, one neurologist and one intentive care physician was conveyed. A methodologist leaded the process. An external panel of 7 members revised the final manuscript. Overall 27 clinical questions were developed and transplanted from narrative to PICO format. Critical outcomes for eligibility PICOs were selected: overall survival (OS), progression-free survival (PFS), quality of life (QOL), cytokine release syndrome grade 3-4 (CRS), neurotoxicity any garde (ICANS). Systematic literature review was conducted for each question (Marchetti, Blood 2022). The process was based on the GRADE-based Methodology Manual by the Italian National Guideline System.
RESULTS: The EP developed 2 strong positive evidence-based recommendations based on the below PICO: ""Is CD19 CAR-T therapy recommended for adult patients with R/R (2 prior treatment lines) LBL/MCL in order to mazimize the ratio between desirable effects (OS, PFS, QOL) and undesirable effects (CRS, ICANS)?"" The EP reckoned the poor quality of evidence for QOL. Considerations of CAR-T-driven healthcare resource use was based on available country-specific HTAs. Moreover, the EP developed 23 Good Practice Recommendations, included an innovative recommendation to the use of Anakinra form managing CART-related toxicities. The full report of the CPG was published (https://www.iss.it/-/terapia-cart-anti-cd19-nei-linfomi-b-aggressivi) and disseminated.
CONCUSIONS: Evidence-based recommendations for CAR-Ts were developed, but the quality evidence for QOL needs an improvement.
"
Chimeric-antigen receptor T-cell therapies (CART) are autologus reingeneered lymphocytes campable of targeting neoplasic lymphoid cells and achieve a high rate of response in refractory/relapsed (R/R) large B-cell lymphomas (LBL) and mantle cell lymphomas (MCL). The economic and safety drawbacks of CARTs impose a careful selection of patients, however, no randomized clinical trial compared CART to standard of care therapies (SOC), therefore direct evidence is missing. The Italian Ministry of Health invited the national scientific societies to develop GRADE-based clinical pratice guidelines (CPG) for the most relevant clinical issues. The CPG undergo a revision process and are finally published.
OBJECTIVES: The Italian Society of Hematology planned to develop GRADE-based recommendations for CARTs in the setting of R/R LBL and MCL. Satellite scientific societies (GITMO, SIDEM) were invited to contribute to the process.
METHODS: An Expert Panel (EP) of 7 hematologist, 1 transplant nurse, one neurologist and one intentive care physician was conveyed. A methodologist leaded the process. An external panel of 7 members revised the final manuscript. Overall 27 clinical questions were developed and transplanted from narrative to PICO format. Critical outcomes for eligibility PICOs were selected: overall survival (OS), progression-free survival (PFS), quality of life (QOL), cytokine release syndrome grade 3-4 (CRS), neurotoxicity any garde (ICANS). Systematic literature review was conducted for each question (Marchetti, Blood 2022). The process was based on the GRADE-based Methodology Manual by the Italian National Guideline System.
RESULTS: The EP developed 2 strong positive evidence-based recommendations based on the below PICO: ""Is CD19 CAR-T therapy recommended for adult patients with R/R (2 prior treatment lines) LBL/MCL in order to mazimize the ratio between desirable effects (OS, PFS, QOL) and undesirable effects (CRS, ICANS)?"" The EP reckoned the poor quality of evidence for QOL. Considerations of CAR-T-driven healthcare resource use was based on available country-specific HTAs. Moreover, the EP developed 23 Good Practice Recommendations, included an innovative recommendation to the use of Anakinra form managing CART-related toxicities. The full report of the CPG was published (https://www.iss.it/-/terapia-cart-anti-cd19-nei-linfomi-b-aggressivi) and disseminated.
CONCUSIONS: Evidence-based recommendations for CAR-Ts were developed, but the quality evidence for QOL needs an improvement.
"