PURPOSE: Treatment options for @entity1 with relapsed or refractory chronic @entity2214 (R/R CLL) are limited. Until recently, few effective treatment options existed, and even with the advent of new agents, studies evaluating comparative efficacy are scarce. In the @entity6490 Versus Ofatumumab in @entity1 With Relapsed or Refractory @entity1072 (RESONATE) Phase III study, @entity6490 , an oral, once-a-day, first-in-class covalent Bruton @entity4149 kinase inhibitor, improved progression-free survival (PFS) and @entity1349 ( @entity1349 ) compared with ofatumumab (PFS hazard ratio [HR] = 0.106 and @entity1349 HR = 0.369 [adjusted for crossover] at a median of 16 months' follow-up). We sought to establish the relative efficacy of @entity6490 versus other treatment options for @entity1 with R/R CLL using indirect comparison methods. METHODS: A systematic literature review was conducted to identify clinical trials sharing a common treatment arm with the RESONATE Phase III trial such that a network meta-analysis or indirect treatment comparisons (ITCs) could be conducted. Two trials were identified, each using the same comparator (ofatumumab) as the RESONATE study. Two pairwise ITCs were conducted using the Bucher method to establish the relative treatment efficacy of @entity6490 versus (1) idelalisib plus ofatumumab in the first study and (2) physician's choice, defined as a mix of therapies commonly used in R/R CLL, in the second study. Odds ratios for these ITCs were calculated for overall response rate (ORR) and HRs for PFS and @entity1349 . FINDINGS: A strong and consistent trend of superiority for @entity6490 was observed via these ITC models with idelalisib plus ofatumumab and physician's choice for ORR, PFS, and @entity1349 . @entity6490 revealed prolonged PFS and @entity1349 versus comparators (PFS HR = 0.06; 95% CI, 0.04-0.11; and @entity1349 HR = 0.25; 95% CI, 0.12-0.54), physician's choice (PFS HR = 0.41; 95% CI, 0.25-0.66; and @entity1349 HR = 0.50; 95% CI, 0.23-1.08), and idelalisib plus ofatumumab. These findings were robust and continued to favor @entity6490 when adjusting (where appropriate) for underlying differences in @entity1 population between the trials. Some trial differences were not accounted for in the models and thus some limitations remain; however, consistency of results supports the overall findings. IMPLICATIONS: In a randomized Phase III study, @entity6490 significantly improved ORR, PFS, and @entity1349 in @entity1 with R/R CLL versus ofatumumab. In ITC models that used ofatumumab as the common comparator, @entity6490 appears to have higher ORR and longer PFS and @entity1349 versus both idelalisib plus ofatumumab and physician's choice. In the absence of head-to-head studies and taking into consideration inherent limitations of ITCs, these models provide useful estimates of comparative efficacy.

Indirect Treatment Comparisons of @entity6490 Versus Physician's Choice and Idelalisib Plus Ofatumumab in @entity1 With Previously Treated XXXX .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'patient'] @entity2214 :: ('MESH:D007945', 'Disease') :: ['lymphocytic leukemia'] @entity1072 :: ('MESH:D015451', 'Disease') :: ['Chronic Lymphocytic Leukemia'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'overall survival'] @entity6490 :: ('MESH:C551803', 'Chemical') :: ['Ibrutinib', 'ibrutinib']
@entity1072 :: (MESH:D015451,Disease) :: ['Chronic Lymphocytic Leukemia']
