Assessment of Healthcare Resource Utilization and Hospitalization Costs in Patients With Relapsed or Refractory Follicular Lymphoma Undergoing CAR-T Cell Therapy With Tisagenlecleucel: Results From the ELARA Study.

Follicular lymphoma (FL) is generally considered an indolent disease, although patients with relapsing FL experience progressively shorter durations of response to second or later lines of therapy. The ongoing ELARA trial in adult patients with relapsed/refractory (r/r) FL treated with tisagenlecleucel demonstrated an overall response rate of 86.2% and a complete response rate of 69.1%, with no treatment-related deaths. Tisagenlecleucel was administered in the outpatient setting in 18% of patients in ELARA; however, there is limited knowledge concerning the impact of inpatient versus outpatient tisagenlecleucel administration on healthcare resource utilization (HCRU) among patients with r/r FL. Here, we present the first HCRU analysis among patients with r/r FL who received tisagenlecleucel in the Phase II, single-arm, multicenter ELARA trial. HCRU was characterized using hospitalization data from day 1 to month 2 after tisagenlecleucel infusion. Information on length of stay, facility use, and discharge was assessed in patients who received tisagenlecleucel in the outpatient or inpatient setting. All costs were inflated to 2020 US dollars. As of August 3, 2021 (20-month median follow-up), 17/97 (18%) r/r FL patients were infused in an outpatient setting. Patients infused in the outpatient setting generally had favorable Eastern Cooperative Oncology Group performance status and Follicular Lymphoma International Prognostic Index scores, and less bulky disease at baseline. However, the outpatients had higher proportions of patients with grade 3A FL, primary refractory disease, and >5 lines of prior therapy compared with inpatients. Forty-one percent of patients treated in the outpatient setting did not require hospitalization within 30 days after infusion, and outpatients who did require hospitalization had a shorter average length of stay compared with inpatients (5 versus 13 days). No outpatients required intensive care unit (ICU) admission, whereas 9% of inpatients were admitted to the ICU. The mean postinfusion hospitalization costs were $7477 and $40,054 in the outpatient and inpatient settings, respectively. Efficacy between both groups was similar. Tisagenlecleucel can be safely administered to some patients in the outpatient setting, which may reduce HCRU for patients with r/r FL.

Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK Inhibition as an Effective Strategy.

PURPOSE: Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood. EXPERIMENTAL DESIGN: To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies]. RESULTS: We identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n = 130), and 81% were idelalisib naïve (n = 263). ORR to BTKi was 84% (n = 44) in BTKi-naïve patients versus 54% (n = 30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons. CONCLUSIONS: For BTKi-naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.See related commentary by Rogers, p. 3501.

Determinants of the optimal first-line therapy for follicular lymphoma: a decision analysis.

Combination immunochemotherapy is the most common approach for initial therapy of patients with advanced-stage follicular lymphoma, but no consensus exists as to the optimal selection or sequence of available regimens. We undertook this decision analysis to systematically evaluate the parameters affecting the choice of early therapy in patients with this disease. We designed a Markov model incorporating the three most commonly utilized regimens (RCVP, RCHOP, and RFlu) in combinations of first- and second-line therapies, with the endpoint of number of quality-adjusted life years (QALYs) until disease progression. Data sources included Phase II and Phase III trials and literature estimates of long-term toxicities and health state utilities. Meta-analytic methods were used to derive the values and ranges of regimen-related parameters. Based on our model, the strategy associated with the greatest number of expected quality-adjusted life years was treatment with RCHOP in first-line therapy followed by treatment with RFlu in second-line therapy (9.00 QALYs). Strategies containing RCVP either in first- or second-line therapy resulted in the lowest number of QALYs (range 6.24-7.71). Sensitivity analysis used to determine the relative contribution of each model parameter identified PFS after first-line therapy and not short-term QOL as the most important factor in prolonging overall quality-adjusted life years. Our results suggest that regimens associated with a longer PFS provide a greater number of total QALYs, despite their short-term toxicities. For patients without contraindications to any of these regimens, use of a more active regimen may maximize overall quality of life.