denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III
Hematology Disease Topics & Pathways:
Technology and Procedures, imaging, molecular testing
Methods: NDTEMM patients ≤ 65 years were randomized to receive carfilzomib, lenalidomide, dexamethasone (KRD) induction – autologous stem cell transplantation (ASCT) intensification-KRd consolidation (arm A); KRd12 (arm B) and carfilzomib, cyclophosphamide, dexamethasone (KCd) induction-ASCT intensification-KCd consolidation (arm C). Thereafter, patients were randomized to maintenance with lenalidomide alone or plus carfilzomib. PET/CT scans were performed locally at baseline (B) and prior to the start of maintenance (PM). DS were applied both in the BM and FLs, as previously described (Zamagni E, EHA 2020). CMR was defined as DS < 4 both in the FLs and BM. MRD evaluation was performed by 8-color second-generation flow cytometry (sensitivity 10-5) in patients who achieved at least VGPR before maintenance (Gay F, ASCO 2019). The impact of each parameter on outcomes was evaluated by landmark analyses at PM. A multivariable Cox regression analysis was adopted to identify independent predictors for PFS and OS.
Results: 182 out of the 474 global patients enrolled in the trial had a pre- and post-treatment PET/CT evaluation available and were included in this analysis. Patients’ baseline characteristics were: median age 57 years, ISS and R-ISS stage III 18% and 10%, respectively, high-risk cytogenetics (t(4;14) ± del(17p) ± t(14;16), detected by FISH) 26%, reflecting baseline clinical features of the entire FORTE population.
At B, 93% of patients had FLs, with a median maximum standardized uptake value (SUVmax) of 5.7 [IQR: 4.1-8.1], 7% presented extra-medullary lesions and nearly all patients had increased BM uptake, with a median SUVmax of 3.4 [IQR: 2.8-4.3]. FS and BMS ≥ 4 were present in 87% and 57% of patients, respectively. At PM, PET/CT negativity according to DS < 4, was present in 80% in the FLs and 85% in the BM, respectively. 63% showed CMR. 92% and 61% of patients achieved ≥ VGPR and CR as best response, respectively, while 73% of them achieved MFC MRD negativity. The achievement of a best CR significantly correlated with BMS < 4 at PM (P= 0.003).
In univariate analysis, at Landmark time PM, FS <4 significantly influenced both PFS and OS (survival probability at 36 mos 78% vs 68%, HR 0.32, CI 0.15-0.68, P= 0.003; 94% vs 80%, HR 0.28, CI 0.09-0.93, P= 0.038, respectively). Achievement of CMR was a strong predictor for prolonged PFS (survival probability at 36 mos 79% vs 58%, HR 0.38, CI 0.18-0.81, P= 0.012), with a trend on OS (survival probability at 36 mos 92% vs 87%, HR 0.34, CI 0.10-1.22, P= 0.099) (fig.1). Patients achieving both PET/CT CMR and MFC negativity at PM showed significantly extended PFS and OS (survival probability at 36 mos 86% vs 55%, HR 0.21, CI 0.09-0.49, P<0.001; 96% vs 76%, HR 0.17, CI 0.04-0.78, P= 0.023, respectively) compared to all the others (fig.2). In Cox multivariable analysis achievement of CMR and MFC MRD negativity were independent predictors of both PFS and OS (HR 0.17, CI 0.07-0.42, P< 0.001 and HR 0.21, CI 0.04-0.97, P= 0.046, respectively for PFS and OS).
Conclusion: In conclusion, the present analysis confirms the applicability and validity of DS criteria to define PET/CT CMR in an independent prospective series of NDTEMM patients. CMR significantly and independently correlated in uni- and multivariable analysis with patient’s outcomes in terms of PFS and OS and was complementary to the MFC MRD negativity.
Disclosures: Zamagni: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau; Takeda: Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau. Gay: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. D'Agostino: GSK: Membership on an entity's Board of Directors or advisory committees. Galli: Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria; BMS: Honoraria. Zambello: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Rivolti: Celgene: Membership on an entity's Board of Directors or advisory committees. Tacchetti: Bristol-Myers Squibb: Honoraria; AbbVie: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Oncopeptides: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Fanti: Bayer, Astellas, GE Healthcare, ANMI, Janssen: Membership on an entity's Board of Directors or advisory committees; Bayer, Astellas, GE Healthcare, Sanofi, AAA: Honoraria. Boccadoro: Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Cavo: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria. Musto: Amgen: Honoraria; Celgene: Honoraria. Oliva: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria.