Background: Optimal consolidation for young patients with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase 3 FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) to ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance (RM). Patients and methods: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1:1 to ASCT or RIT before CD34+ collection, and all received post-consolidation RM. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group). Results: During Aug 2012-Sept 2019, of 164 screened patients, 159 were enrolled (median age 57 [49-62] years, 55% male, 57% stage IV, 20% bulky disease). The study was closed prematurely because of low accrual. Data were analyzed on June 8, 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. Estimated 3-yrs PFS in both groups was 62% (HR 1.11, 95% CI 0.69-1.80, P = 0.6662). Three-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT vs 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% vs 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189). Conclusion: Even if prematurely discontinued, our study did not demonstrate superiority of ASCT vs RIT. ASCT was more toxic and demanding for patients and health service. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.
Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapse/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase 3 trial
Ladetto, M;Tavarozzi, R;Gaidano, G;
In corso di stampa
Abstract
Background: Optimal consolidation for young patients with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase 3 FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) to ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance (RM). Patients and methods: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1:1 to ASCT or RIT before CD34+ collection, and all received post-consolidation RM. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group). Results: During Aug 2012-Sept 2019, of 164 screened patients, 159 were enrolled (median age 57 [49-62] years, 55% male, 57% stage IV, 20% bulky disease). The study was closed prematurely because of low accrual. Data were analyzed on June 8, 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. Estimated 3-yrs PFS in both groups was 62% (HR 1.11, 95% CI 0.69-1.80, P = 0.6662). Three-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT vs 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% vs 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189). Conclusion: Even if prematurely discontinued, our study did not demonstrate superiority of ASCT vs RIT. ASCT was more toxic and demanding for patients and health service. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
