Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells.

The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P<0.001) than patients with low TMTV. Multivariable analyses identified baseline elevated lactate dehydrogenase, DS-5, CAR T cells at M1 for PFS and baseline elevated lactate dehydrogenase, TMTV >80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.

Economic burden in non-Hodgkin lymphoma survivors: The French Lymphoma Study Association SIMONAL cross-sectional study.

BACKGROUND: No study has focused on the economic burden in non-Hodgkin lymphoma (NHL) survivors, even though this knowledge is essential. This study reports on health care resource use and associated health care costs as well as related factors in a series of 1671 French long-term NHL survivors. METHODS: Health care costs were measured from the payer perspective. Only direct medical costs (medical consultations, outpatient treatments, hospitalizations, and medical transport) in the past 12 months were included (reference year 2015). Multiple linear regression was used to search for explanatory factors of health care costs. RESULTS: In total, 1100 survivors (66%) reported having used at least 1 health care resource, and 867 (52%) reported having used at least 1 outpatient treatment. After the authors accounted for missing data, the mean health care cost was estimated at €702 ± €2221. Hospitalizations and outpatient treatments were the main cost drivers. Sensitivity analyses confirmed the robustness of the results. For the 1100 survivors who reported using at least 1 health care resource, the mean health care cost was €1067 ± €2268. Several factors demonstrated statistically significant relationships with health care costs. For instance, cardiovascular disorders increased costs by 66% ± 16%. In contrast, rituximab or autologous stem cell transplantation as initial therapy had no effect on health care costs. CONCLUSIONS: The consideration of economic constraints in health care is now a reality. This retrospective study reports on a better understanding of health care resource use and associated health care costs as well as related factors. It may help health care professionals in their ongoing efforts to design person-centered health care pathways.

Prognostic value of high-sensitivity measurable residual disease assessment after front-line chemoimmunotherapy in chronic lymphocytic leukemia.

Measurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10-5) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD < 0.01% to MRD ≥ 0.01% increased the proportion of cases with positive MRD in blood by 39% and in bone marrow by 27%. Compared to low-level positive MRD < 0.01%, undetectable MRD was associated with significantly longer progression-free survival (PFS) when using blood (72.2 versus 42.7 months; hazard ratio 0.40, p = 0.0003), but not when using bone marrow. Upon further stratification, positive blood MRD at any level, compared to undetectable blood MRD, was associated with shorter PFS irrespective of clinical complete or partial remission, and a lower 5-year PFS rate irrespective of IGHV-mutated or -unmutated status (all p < 0.05). In conclusion, high-sensitivity (0.0007%) MRD assessment in blood yielded additional prognostic information beyond the current standard sensitivity (0.01%). Our approach provides a model for future determination of the optimal MRD investigative strategy for any regimen.

[Conduct of epidemiologic studies in French cancer survivors: Methods, difficulties encountered and solutions provided. Lessons learned from the SIMONAL study on long-term toxicities after non-Hodgkin lymphoma treatment]. / Conduire des études épidémiologiques après cancer en France : modalités, difficultés et propositions de solutions. Les enseignements de l'étude SIMONAL sur les toxicités tardives des traitements du lymphome non Hodgkinien.

INTRODUCTION: Since the introduction of targeted therapies, specific lymphoma mortality has decreased. Possible long-term toxicities, however, are not known yet. This article describes the implementation of the SIMONAL study that investigates the hypothesis of an overconsumption of care after lymphoma treatment with a 10-year follow-up. METHODS: After the mandatory regulatory steps (CCTIRS and CNIL) the vital status and address of 5247 patients treated in 131 French centers were retrieved using a secure web portal, in order to send a quality of life after lymphoma questionnaire. After an additional vital status validation request at the center for epidemiologic research and population health (CESP), the questionnaires were sent. Double data entry was performed on the collected data and a request to access data from France's public health insurance scheme information system (SNIIRAM) was formulated. RESULTS: Retrieval of the addresses via the portal has been slow and multiple reminders were needed. The CESP identified 9.4 % additional deaths not known by the treatment centers. Of the 3391 questionnaires sent, the response rate was 50%. A comparison between the responders and non-responders revealed no demographic differences but showed that the responders were more often treated with targeted drugs as they were included in more recent trials. DISCUSSION: Logistic and information technology (IT) aspects rendered the implementation of the SIMONAL study more complex, time consuming and costly. However, using the collected data, many future research questions will be addressed.

Management of elderly patients with chronic lymphocytic leukemia in the era of targeted therapies.

PURPOSE OF REVIEW: Chronic lymphocytic leukemia (CLL) is frequently diagnosed after 71 years, though median age in published clinical trials with standard chemoimmunotherapy regimens in frontline or relapse setting is mostly below 70 years (58-71 years). Development of oral, less toxic and thus more affordable targeted therapies offers new therapeutic options in those patients deemed unfit for chemotherapy. RECENT FINDINGS: This review will discuss results of these new agents in the therapy of elderly patients. Apart from discussing the impact of chronological age, creatinine clearance and cumulative illness rating scale scores in the clinical outcomes, we will also discuss how individualized treatment decision-making should include more precise geriatric assessment tools to thoroughly assess life expectancy, anticipate tolerability, to avoid deleterious stress precipitating prefrail patients into definitive loss of capacity, with dramatic social and economic costs. SUMMARY: In the era of new targeted agents to fight cancers, we propose concepts to help us understand how elderly dedicated trial designs and geriatric assessment tools (apart from the evaluation of CLL biological risk factors) will undoubtedly revolutionize therapeutic approaches in everyday practice CLL patients.