In the phase 3 DUO clinical trial, treatment with duvelisib improved health-related quality of life in patients with relapsed or refractory chronic lymphocytic leukemia compared with ofatumumab.
Duvelisib (Copiktra) treatment led to better health-related quality of life (QoL) outcomes in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) compared with ofatumumab (Arzerra), according to an analysis of the phase 3 DUO trial (NCT02004522).
Patient-reported outcomes (PROs) for the analysis were categorized as physical well-being, social/family well-being, emotional well-being, and functional well-being. A score of all categories combined was compiled into 1 functional assessment of chronic: general (FACT-G) score. Investigators led by Pier Luigi Zinzani also had a functional assessment of chronic illness therapy-fatigue (FACIT-F) score. All PRO analyses were carried out on day 1 of cycles 3, 5, 7, 11, 15, and 19, until disease progression, patients withdrawal, or the initiation of additional anticancer therapy.
Regarding the mean PRO scores, all favored duvelisib over ofatumumab. The FACT-G total difference in means was 2.3 and the differences in medians was 5.2 (P = .0109), in the previously treated population. In the intent-to-treat population, the FACT-G Total difference in means was 1.55 and the difference in medians was 2.59 (P =.0534). FACIT-Fatigue was had a 1.7 differences in means and a 1.3 difference in medians among previously treated patients (P =.0657). For intent-to-treat patients, the FACIT-Fatigue difference in means was 0.52 and the difference in medians was -0.43 (P = .2197).
The FACIT-F trial outcomes index score showed a 3.6 difference in means and a 4.8 difference in medians (P = .0123), in the previously treated population. The FACIT-F differences in means for the intent-to-treat (ITT) population was 1.04 and the difference in medians was 3.07 (P = .2692). Finally, the FACIT-F Total score demonstrated a 4.1 difference in means and a 6.1 difference in medians (P = .0052) among previously treated patients. There was a difference in means of 2.1 and a difference in medians of 2.87 (P =.0486) in the ITT population.
The difference observed between duvelisib and ofatumumab with the mean PRO scores over time was statistically significant in 6 out of 10 scales. In addition, there was a clinically meaningful difference as measured by the EuroQuol 5-D (EQ-5D).
Change in PROs from baseline was also evaluated during the analysis. The categories for change included better, same, or worse.
In the patients with 2 or more lines of prior therapy, according to the EQ-5D index, worsening PROs were observed in 11% of patients who received duvelisib compared with 21% of those who received ofatumumab. The difference was -9% (CI -16% to -3%; P =.005). On the EQ-5D VAS scale, 4% of patients in the duvelisib arm had worsening PROs compared with 15% of the ofatumumab arm, which had a difference of -11% (CI, -16% to 6%; P =.0001).
Regarding patient-reported well-being, there was difference no between the duvelisib arm and the ofatumumab arm on the FACT Emotional Well-Being scale. On the FACT Functional Well-Being scale, the worsening rate was 15% versus 18% (CI, -9% to 4%; P =.4061). The FACT Physical Well-Being scale showed a worsening rate of 6% in the duvelisib group versus 10% in the ofatumumab group (CI, -9% to 0%; P =.0715). The remaining well-being PRO was social and family well-being, which, according to the FACT scale, favored the duvelisib group at 13% worsening versus 17% (CI, -10% to 3%; P =.2717).
The FACT-G Total worsening rate among patients who received duvelisib was 13% versus 19% among those who received ofatumumab (CI, -12 to 1%; P =.0826). Per the FACIT-Fatigue scale, worsening PROs occurred in 4% of the duvelisib arm versus 9% of the ofatumumab arm (CI, -9% to -1%; P = .0149).
The ITT population had similar change analysis results to the population of patients with 2 or prior lines of therapy. According to the EQ-5D index scale, the worsening rate was 13% with duvelisib versus 17% with ofatumumab (CI, -9% to 1%, P =.1325). On the EQ-5D VAS scale, the difference in the PRO worsening rate in the duvelisib arm versus the ofatumumab arm was 7% versus 10% (CI, -7% to 0%, P = .0912).
Well-being in the ITT population varied with some changes favoring duvelisib-treated patients and others favoring ofatumumab-treated patients. Per the FACT Emotional Well-Being scale, the PRO worsening rate was 8% in the duvelisib group versus 2% in the ofatumumab group (CI, -2% to 5%, P = .3734). On the FACT Functional Well-Being scale, the difference is worsening PROs in the duvelisib arm versus the ofatumumab arm was 17% versus 16% (CI, -4% to 6%, P = .6481). In terms of physical well-being, the FACT scale showed a worsening rate of 8% with duvelisib compared with 9% in the ofatumumab arm (CI, -5 to 2%; P = .5368). In terms of social and family well-being, the FACT scale showed a 17% worsening rate in the duvelisib arm compared with 16% in the ofatumumab arm (CI, -4% to 6%; P = .7081).
The FACT-G Total scale revealed a worsening rate of 18% with duvelisib versus 2% with ofatumumab (CI, -3% to 8%; P =.3476). According to the FACIT-Fatigue scale, the difference in PRO worsening between the duvelisib and ofatumumab arms was 6% versus 8%, respectively (CI, -5% to 2%; P =.3533). Finally, the FACIT-F Trial Outcome Index scale showed a 4% worsening rate in the duvelisib arm compared with 3% in the ofatumumab arm (CI, -1% to 3%; P = .3318).
Improvements in PROs from baseline in all patients were measured. The time to response was similar between the 2 agents, but the probability of response was higher in the duvelisib treatment arm, except as measured by the FACIT-F Total scale. On the other hand, the probability of failure was estimated to be higher in the ofatumumab treatment arm.
Overall, Zinzani et al found that duvelisib was consistently better than ofatumumab in terms of PROs among the subset of patients who received 2 or more prior lines of treatment. However, the ITT population demonstrated smaller magnitudes of difference between treatment with duvelisib and ofatumumab, which usually meant they lacked any statistical significance.
The results imply that the use of duvelisib as treatment of patients with relapsed/refractory CLL or SLL does not damage functioning compared with ofatumumab. This holds true even when exposure duvelisib is longer than ofatumumab.
Duvelisib monotherapy was administered at a dose of 25 mg twice daily in the DUO study. There was a total of 94 patients in the duvelisib arm who had 2 more prior lines of treatment and 156 who were in the ITT population. The control arm had 97 patients in the arm of 2 or more prior treatments and 146 in the ITT group.
The overall efficacy results of the study were previously announced, demonstrating a significant improvement in the primary end points progression-free survival (PFS), as well as, the overall response rate. In the ITT population, the median PFS was 13.3 compared with 9.9 months in the control arm (HR, 0.52; P <.0001).
Patients were exposed to duvelisib for a median of 11.6 months, which was higher than the control drug, which patients were exposed to for a median of 5.3 months.
The safety profile observed with duvelisib in DUO was manageable and consistent with previous reports. Some interventions like dose modifications were necessary.
Duvelisib is approved by the FDA for the treatment of patients with R/R CLL and SLL who had at least 2 prior lines of therapy, which was granted based on the phase 2 DYNAMO study (NCT01882803). The agent is also FDA-approved for the treatment of patients with follicular lymphoma who have had at least 2 prior lines of therapy.
Zinzani PL, Jager U, Lustgarten S, et al. Patient-reported outcomes and quality of life in duo: a randomized trial of duvelisib vs. ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Presented at: 2020 European Hematology Association Virtual Congress; June 11-21, 2020. Accessed June 29, 2020. https://bit.ly/2YJX0NZ