With the development of cutting-edge drugs like Ibr, the treatment landscape for CLL/SLL has swiftly changed. The biggest US-based prospective, observational registry of patients (pts) beginning FDA-approved therapy for CLL/SLL in the period following Ibr approval was the informCLL registry. For a study, researchers sought to provide real-world (RW) results from the informCLL final analysis in patients with CLL/SLL undergoing first-line (1L) treatment, including a comparison of 1L Ibr versus CIT.
Patients with CLL/SLL who began FDA-approved therapy (within ±45 days of enrolment) between October 2015 and June 2019 were included in the study. Patients were predominantly enrolled through practices in the community (93% of locations). Data about baseline characteristics, treatment trends, and safety were gathered. Time to next treatment (TTNT) estimates were made using the Kaplan-Meier technique and Cox proportional hazards regression analysis in weighted cohorts to compare outcomes between 1L Ibr and CIT. To balance baseline characteristics across cohorts, inverse probability of treatment weighting (IPTW) was used. Adverse events (AEs) were assessed using overall incidence and exposure-adjusted incidence rates (EAIRs).
About 854 of the 1,459 eligible patients that were recruited and treated received 1L care, or 59% of the total. In the entire 1L cohort, the median age was 70 years (≥75 years in 33%); 90% had an ECOG performance status of 0/1; 47% had Rai stage III/IV (among the n=547 with Rai staging); the median Charlson Comorbidity Index (CCI) score was 1 (range 0-12); CCI ≥3 in 16%, and the median time from the initial diagnosis to 1L treatment was 19 mo. In the 1L cohort, 57% of patients had FISH testing results available; 12% of these patients had del (17p). Ibr (45%; single-agent Ibr in 43% of all 1L therapies) and CIT (43%; most frequently BR, 24%) were the most popular 1L treatments, followed by immunotherapy (11%), chemotherapy (0.9%), and other new drugs (0.7%). In the 1L cohort, median TTNT was not reached (NR) at 31.8 months; the estimated proportions of patients without next-line treatment (NLT) were 79% at 24 months, 71% at 36 months, and 64% at 48 months. With a median follow-up of 31.4 months for the Ibr cohort and 34.3 months for the CIT cohort, the 1L cohort included 383 patients treated with Ibr and 363 patients treated with CIT. Patients in the Ibr cohort were older, had a longer interval between diagnosis and therapy, had a history of previous malignancies, and were more likely to have del(17p) or TP53 mutations than those in the CIT group. The weighted cohorts’ baseline attributes were evenly distributed. Ibr enhanced TTNT compared to CIT in the IPTW-adjusted groups, with a median TTNT of NR and 56.5 mo, respectively (hazard ratio: 0.744; 95% CI: 0.563-0.981). Estimated percentages of the weighted Ibr cohort who were free of NLT at 36 and 48 months were 75% and 69%, respectively, whereas rates for the weighted CIT cohort were 66% and 57%. The median length of the index therapy was 4.7 months for CIT and 24.0 months for 1L Ibr. In the Ibr cohort (n=383), major AEs occurred in 144 patients (38%), most often (≥3% of patients) pneumonia (n=23; 6%) and atrial fibrillation (n=21; 5%); AEs resulted in Ibr cessation in 135 patients (35%), most frequently due to weariness (n=12; 3%) and Afib (n=19; 5%). Around 85 patients (23%) in the CIT cohort (n=363) experienced significant adverse events (AEs). The most prevalent AEs were febrile neutropenia (n=13; 4%) and pneumonia (n=11; 3%). A total of 61 patients (17%) discontinued CIT due to AEs, and only ≥3% of patients (2% of whom had anemia) discontinued due to a single AE term. Serious AEs had EAIRs per 100 points per month of 1.93 with Ibr and 4.55 with CIT. EAIRs for AEs that resulted in discontinuation were 1.53 with Ibr and 3.09 with CIT per 100 pt-mo.
Results from IPTW-adjusted analysis in this sizable RW registry of patients with CLL/SLL revealed that 1L Ibr was linked with a longer TTNT than CIT, with a sustained benefit up to 4 years of follow-up. In comparison to patients receiving CIT, patients getting 1L Ibr treatment tended to be older, more likely to have a history of another cancer, and more likely to have high-risk genetic characteristics (such as del(17p) or TP53 mutation). Data from clinical studies and other RW studies appeared to be consistent with the range and frequency of AEs seen with these 1L regimens. Rates of serious AEs and AEs leading to discontinuation were lower with Ibr than CIT when exposure was taken into account. Future studies evaluating how age, comorbidities, and race affect RW outcomes in patients with CLL/SLL were necessary to advance the knowledge of these outcomes.