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.

Higher symptom burden is associated with lower function in women taking adjuvant endocrine therapy for breast cancer.

OBJECTIVE: To explore the impact of symptoms on physical function in women on adjuvant endocrine therapy for breast cancer. METHODS: Eligible women were postmenopausal, had hormone receptor positive, stage I-IIIA breast cancer, completed surgery, chemotherapy, radiation, and on adjuvant endocrine therapy. At a routine follow-up visit, women (N = 107) completed standardized symptom measures: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy Neurotoxicity scales. Two performance measures assessed function: grip strength (Jamar dynamometer; n = 71) and timed get-up-and-go (TUG; n = 103). Analyses were performed with an overall symptom composite score. Correlations and multiple linear regression analyses were performed to test adverse effects on physical function. RESULTS: The mean age was 64 years (range 45-84), 81% white, 84% on an aromatase inhibitor, and on endocrine therapy for mean 35 months (range 1-130 months). Dominant hand grip strength was inversely correlated with symptom composite scores (r = -0.29, p = .02). Slower TUG was positively correlated with higher Charlson comorbidity level (r = 0.36, p < .001) and higher symptom composite scores (r = 0.24, p = .01). In multivariate analyses, weaker dominant and non-dominant hand grip strength were significantly associated with greater symptom composite scores (ß = -0.27, t = 2.43, p = .02 and ß = -0.36, t = 3.15, p = .003, respectively) and slower TUG was associated with higher symptom composite scores (ß = 0.18, t = 1.97, p = .05). CONCLUSIONS: Higher symptom burden is associated with worse physical function, as measured by hand grip strength and TUG. Further study to determine the impact of endocrine therapy and its side effects on function is warranted.

Health-Related Quality of Life: The Impact on Morbidity and Mortality.

In the age of ever-expanding treatments and precision medicine, the hope for cure remains the ultimate goal for patients and providers. Equally important to many patients is the quality of life achieved during and after treatment. Evidence suggests that overall quality of life is important to patients and plays a role in determining outcomes in patients with cancer. This article examines components of health-related quality of life and cancer treatment, including physical, psychosocial, and financial burden, as well as how these components affect patients' overall wellbeing and survival.