Page 173 - Haematologica Vol. 109 - July 2024

ARTICLE - ASCT in refractory or early relapsed DLBCL
A.M. Tun et al.
new standard of care in the second-line setting.15-17 However, there are still significant challenges and barriers to timely delivery of CAR-T therapy in routine clinical practice. CAR-T therapy, to date, is mainly offered in major referral centers, and patients often need to travel long distances for evaluation for such therapy. Patients also need to spend weeks to months for eligibility and fitness assessment, in- surance approval, CAR-T manufacturing, and other logistical planning.18,19 A substantial number of patients experience symptomatic, life-threatening progressive disease before receiving CAR-T therapy and often require urgent systemic chemotherapy in the form of a salvage or bridging therapy.19 Moreover, clinical activities of CAR-T therapy remain modest in the second-line setting, with the median event-free sur- vival being only 8.3 months with axicabtagene ciloleucel in ZUMA-7 and 10.1 months with lisocabtagene maraleucel in TRANSFORM; the majority of patients treated with CAR-T in both studies experienced a relapse.15,17 Furthermore, CAR-T therapy is associated with significant morbidities such as cytokine release syndrome, neurotoxicity, and cytopenia, and its long-term complications remain a major concern.19 Given the challenges and barriers as well as the modest clinical activities of CAR-T therapy, there is a need to explore alternative strategies and identify patients who can truly benefit from HDT and ASCT. It is well understood that ASCT (or rescue) enables the use of HDT, in patients with proven chemosensitive disease, to eradicate residual lymphoma cells that have evaded ST.20 Autologous CAR-T therapy uti- lizes genetically modified patient’s T cells, directed against CD19 antigen on lymphoma cells, for its therapeutic effect.15,17 Accordingly, fit patients with chemosensitive disease can benefit from consolidation with HDT and ASCT, unlike those with chemoresistant disease.11,21 We, therefore, hypothesized that HDT and ASCT would be beneficial and preferable in patients with proven chemosensitive disease after one line of ST, and those with a later relapse 6-12 months after completing frontline immunochemotherapy. To verify this hypothesis, we conducted a retrospective study of patients with refractory disease or relapse within 12 months of com- pleting frontline immunochemotherapy, using information from the Mayo Clinic and the University of Iowa lymphoma and transplant databases.
Methods
Patients
ing physician), and clinical outcome data were extracted by chart reviews.
For this study, eligible patients were those who were treated with frontline R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CHOP-like im- munochemotherapy, had refractory disease (i.e., disease progression during frontline immunochemotherapy or per- sistent disease after completion of frontline therapy) or an early relapse occurring within 12 months of completing frontline immunochemotherapy, and underwent ST and ASCT. Patients whose response to ST was assessed by pos- itron emission tomography and computed tomography scan and achieved a complete response (CR) or partial response (PR), as determined by treating physicians, were included. DLBCL was classified as per hematopathologists in the Mayo Clinic and the University of Iowa. Patients with MYC and BCL2 and/or BCL6 rearrangements (i.e., double-hit or triple-hit lymphoma) and transformed indolent lymphoma at diagnosis were also included, unless previously treated with immunochemotherapy. Patients who did not receive frontline rituximab and those who underwent hematopoi- etic stem cell transplant in the frontline (after achieving complete remission to frontline immunochemotherapy) were excluded.
Statistical analysis
Descriptive statistics are used to report baseline charac- teristics, treatment information, and response status. The reverse Kaplan-Meier method was used to estimate median follow-up time.22,23 Duration of response (DOR) was defined as time from initial response after ASCT to disease progression, relapse, or death. Post-ASCT progression-free survival (PFS) was defined as time from ASCT until progression, relapse, or death from any cause. Post-ASCT overall survival (OS) was defined as time from ASCT to death from any cause. Post-ASCT PFS and OS were plotted using the Kaplan-Meier method. Log-rank tests and Cox proportional hazards mod- els were used to evaluate the impact of clinico-pathological characteristics, treatment variables, and response status on PFS and OS. P values <0.05 were considered statistically significant. Cumulative incidences of relapse and non-re- lapse mortality as well as causes of death were analyzed with competing risk models.24 Causes of death were cate- gorized as a result of lymphoma progression, as a result of treatment-related toxicities, non-lymphoma-related causes (other causes), and unknown causes. Statistical analyses were performed in JMP v16 and XLSTAT v2021.2.
Results
Clinicopathological characteristics of the study population and treatment
A total of 230 eligible patients were included in the study (Online Supplementary Figure S1). The baseline charac-
The institutional review boards at the Mayo Clinic and the University of Iowa approved this study. Data were abstract- ed on consecutive adult patients who underwent ASCT for DLBCL between July 2000 and December 2017 at the Mayo Clinic or between April 2003 and April 2020 at the University of Iowa. Clinical, pathological, molecular characteristics, cell of origin by Hans algorithm, as well as treatment course, clinical response to treatment (as determined by the treat-
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