KEY TAKEAWAYS
- Three clinical studies (RESONATE-2, ECOG1912 and iLLUMINATE) evaluated the efficacy of Ibrutinib (Ibr) monotherapy or combination therapy in patients with untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).
- Pooled data from 603 Ibr-treated patients showed a significantly improved OS rate compared to 424 patients who received chemotherapy and chemoimmunotherapy (CT/CIT) with 3- and 5-year OS rates of 93% and 88%, respectively, versus 85% and 75% for CT/CIT.
- An analysis of 201 Ibr-treated patients aged ≥ 65 at initial CLL diagnosis reported an 8-year OS rate of 78% (95% CI, 71-84) compared to 77% (95% CI, 70-82) for an age-matched general population.
- These results suggest that initiating treatment with 1L Ibr improves OS versus traditional CT/CIT regardless of age or fitness.
Over the past two decades, survival outcomes for patients with chronic lymphocytic leukaemia (CLL) have improved with chemotherapy and chemoimmunotherapy (CT/CIT). In particular, the advent of the novel agent Ibr has been associated with improved outcomes across a range of first-line patient populations, as demonstrated in multiple pivotal trials. Recently presented 8-year follow-up data from the first pivotal trial for Ibr showed that more than half of first-line unfit patients remain progression-free.
Given this, we sought to compare the pooled overall survival (OS) of previously untreated CLL patients treated with Ibr to that of the available age-matched general population and to compare the pooled characteristics and OS results with Ibr versus CT/CIT across three Phase 3 trials. Data were pooled from the RESONATE-2 (NCT01722487), ECOG1912 (NCT02048813), and iLLUMINATE (NCT02264574) clinical studies, which evaluated Ibr alone and in combination with other agents in patients with previously untreated CLL/SLL. Our analysis included 603 patients with previously untreated CLL/SLL who received Ibr treatment across the three pooled studies.
Among those treated with Ibr, 58.7% received Ibr + rituximab, 22.6% received single agent Ibr, and 18.7% received Ibr + obinutuzumab, with a median age of 63 years (range 31-89). We compared the OS of 201 patients aged ≥65 at the time of initial CLL diagnosis to a simulated age-matched OS data cohort from the general population (CDC life table for the total US population in 2019). Overall survival estimates at eight years for Ibr-treated patients aged ≥65 years from the time of CLL diagnosis was 78% (95% CI, 71-84) compared to 77% (95% CI, 70-82) in the age-matched general population [HR, Ibr over the general population, 0.97; 95% CI, 0.63-1.51; p=0.90].
Additionally, pooled data from 603 Ibr-treated patients were compared to data from patients who received CT/CIT (N=424 patients) across the three pooled studies. Among patients who received CT/CIT, 41.3% received fludarabine + cyclophosphamide + rituximab, 31.4% received chlorambucil, and 27.4% received chlorambucil + obinutuzumab, with a median age of 66.5 years (range, 28-90).
Overall survival estimates were significantly improved with Ibr: 3- and 5-year rates were 93% (95% CI, 91-95) and 88% (95% CI, 83-91), respectively, for patients who received Ibr and 85% (95% CI, 81-89) and 75% (95% CI, 68-81), respectively, for patients treated with CT/CIT [HR, Ibr over CT/CIT, 0.46; 95% CI, 0.33-0.66); p<0.0001]. In conclusion, this pooled analysis suggests that initiating therapy with first-line Ibr improves OS compared to traditional CT/CIT, regardless of age or fitness. It is also the first demonstration that patients who start Ibr over an 8-year follow-up have similar survival estimates as age-matched patients in the general population.
Sources:https://ash.confex.com/ash/2022/webprogram/Paper163257.html
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02264574
Paolo Ghia, MD, PhD1, Carolyn Owen, MD2, Jacqueline C. Barrientos, MD, MS3, Paul M. Barr, MD4, Anthony R. Mato, MD, MSCE5, Chunxue Shi, MSc6*, Anita Szoke, MD7*, Chris Abbazio, PharmD7*, Gabriel S. Krigsfeld, PhD7* and Jan A. Burger, MD, PhD8
