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At approximately 5 years of follow-up, findings from the phase 3 ELEVATE-TN study show that treatment outcomes are more favorable with acalabrutinib with or without obinutuzumab compared with obinutuzumab and chlorambucil in treatment-naïve chronic lymphocytic leukemia.
Patients with treatment-naïve chronic lymphocytic leukemia (CLL) who received treatment with acalabrutinib (Calquence) either as a single-agent or in combination with obinutuzumab (Gazyva) elicited a prolonged benefit compared with those who received obinutuzumab plus chlorambucil, according to results of an approximately 60-month follow-up of the phase 3 ELEVATE-TN study (NCT02475681) presented at the 2022 ASCO Annual Meeting.1
Measuring progression-free survival (PFS) was the primary end point of ELEVATE-TN. At the 58.2-month mark (range: 0.0-72.0 months), 59.8% and 64.8% of patients in the acalabrutinib single-agent and acalabrutinib plus obinutuzumab arms remained on treatment, respectively. Moreover, 72 patients who started the trial in the chemoimmunotherapy arm have crossed over to receive single-agent acalabrutinib. Since crossing over, 25% of patients have discontinued single-agent treatment — 10% of discontinuations were due to adverse effects (AEs).
Jeff Sharman, MD, director of research, Willamette Valley Cancer Institute, medical director of hematology research, The US Oncology Network, presented the updated findings.
Enrolled patients (n = 535) were aged 65 years and older, or between 18 to 65 years with certain comorbidities.
Patients (median age, 70 years) were randomized to receive either single-agent acalabrutinib (n = 179), acalabrutinib with obinutuzumab (n = 179) or the chemoimmunotherapy combination (n = 177). Patients enrolled into the chemoimmunotherapy arm were permitted to crossover to the acalabrutinib single-agent arm once study authors confirmed disease progression.
As of this reporting, PFS outcomes favor single-agent acalabrutinib (72%) and acalabrutinib plus obinutuzumab (84%) versus the chemoimmunotherapy regimen (21%). Moreover, a median PFS has not yet been reached for either acalabrutinib arm whereas it is 27.8 months in the chemoimmunotherapy arm.
The findings also demonstrated that the PFS benefit translated to patients who had del(17p) and/or mutated TP53. In this patient population, both the acalabrutinib only and acalabrutinib plus obinutuzumab arm have a PFS rate of 71%. The PFS rate drops significantly to 18% in the chemoimmunotherapy arm.
Overall response rate was also significantly higher in both the acalabrutinib plus obinutuzumab (96.1%; P < .0001) and acalabrutinib only (89.9%; P = .0499) arms compared with the chemoimmunotherapy combo (83.1%). Complete responses also occurred more frequently in the acalabrutinib-containing arms — 32.4% and 14.5% in the acalabrutinib combination and single-agent arm, respectively. Whereas 13.6% of patients in the chemoimmunotherapy arm achieved a complete response.
“The proportion of patients who achieved a complete response, including those with incomplete blood count recovery, were higher in the acalabrutinib-containing arms,” Sharman said during a pre-recorded presentation of the data. “Minimal residual disease was completed only for those patients who achieved complete response.”
Forty-two percent of the patients who achieved a complete response with acalabrutinib plus obinutuzumab had undetectable minimal residual disease (MRD), versus 9% of patients in the chemoimmunotherapy arm.
A median overall survival (OS) has not yet been reached in any of the treatment arms, according to Sharman. However, he said, the authors have observed longer OS in the acalabrutinib plus obinutuzumab arm versus the chemoimmunotherapy arm.
In terms of AEs, Sharman said they remained similar to past analyses of the findings. Cardiac events, bleeding and infections were significantly more likely to occur in both acalabrutinib treatment arms versus the chemoimmunotherapy arm. However, Sharman noted these were also consistent with what has been previously shown.
“We conclude that acalabrutinib demonstrates durability, tolerability, and flexibility to tailor treatment as monotherapy or in combination with obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia,” he said of the findings.
Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: five-year follow-up of ELEVATE-TN. J Clin Oncol. 2022;40(suppl 16):7539. doi: 10.1200/JCO.2022.40.16_suppl.7539