Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL

Abstract

BACKGROUND Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy. METHODS Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met. RESULTS A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients with progression-free survival at 2 years was 74% with bendamustine plus rituximab and was higher with ibrutinib alone (87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.26 to 0.58; P<0.001) and with ibrutinib plus rituximab (88%; hazard ratio, 0.38; 95% CI, 0.25 to 0.59; P<0.001). There was no significant difference between the ibrutinib-plus-rituximab group and the ibrutinib group with regard to progression-free survival (hazard ratio, 1.00; 95% CI, 0.62 to 1.62; P=0.49). With a median follow-up of 38 months, there was no significant difference among the three treatment groups with regard to overall survival. The rate of grade 3, 4, or 5 hematologic adverse events was higher with bendamustine plus rituximab (61%) than with ibrutinib or ibrutinib plus rituximab (41% and 39%, respectively), whereas the rate of grade 3, 4, or 5 nonhematologic adverse events was lower with bendamustine plus rituximab (63%) than with the ibrutinib-containing regimens (74% with each regimen). CONCLUSIONS Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression-free survival. There was no significant difference between ibrutinib and ibrutinib plus rituximab with regard to progression-free survival. (Funded by the National Cancer Institute and Pharmacyclics; ClinicalTrials.gov number, NCT01886872.)

The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia

“…While rates of AEs and dose modifications were similar, older patients discontinued therapy more frequently due to toxicity. This is consistent with prior reports with immunochemotherapy and ibrutinib (Maddocks et al, ; Woyach et al, ) where tolerance may be inferior in elderly patients. We speculate that the maximal tolerated dose in the elderly may be lower.…”

Bendamustine for patients with indolent B cell lymphoproliferative malignancies including chronic lymphocytic leukaemia – an updated meta‐analysis

“…Recently chemotherapy‐free regimens were compared to BR. Ibrutinib with or without rituximab compared to BR were shown to improve PFS of elderly patients with CLL in first line setting, while no statistically significant overall survival difference was demonstrated ( P ≥ 0·65) (Woyach et al , ). Patients had a higher grade 3–5 haematological adverse events rate with BR (61%) than with ibrutinib or ibrutinib‐rituximab (about 40%) P < 0·001.…”

Treating Leukemia in the Time of COVID-19

“…Several novel oral targeted therapies are now available, including ibrutinib, acalabrutinib, and venetoclax. The choice of targeted therapy depends on several patient-and disease-related factors [45][46][47][48][49][50]. Ibrutinib and acalabrutinib generally require fewer clinic/laboratory visits at the time of treatment initiation compared with the venetoclax + obinutuzumab regimen.…”