Phase III GLOW study of Imbruvica + Venclexta shows benefits in chronic lymphocytic leukaemia at 4 years follow-up.- Janssen Pharma

In the study, fixed-duration I+V therapy exhibited robust efficacy in older and/or unfit adults with previously untreated CLL, with a superior and sustained benefit in progression-free survival (PFS) with four years of follow-up. Seventy-five percent of patients treated with the combination were alive and progression-free at 3.5 years. I+V also demonstrated an OS advantage versus Clb+O at this latest study follow-up. Exploratory analyses showed that post-treatment PFS rates were higher for I+V (n=106) than Clb+O (n=105), regardless of minimal residual disease (MRD) status post-treatment.

With a median 46 months of follow-up, I+V reduced the risk of disease progression or death by 79 percent versus Clb+O (Hazard Ratio [HR] 0.214; [95 percent Confidence Interval [CI], 0.138 – 0.334]; p<0.0001). i+v is the first fixed-duration combination to demonstrate an os advantage compared to clb+o in the first-line treatment of cll (hr 0.487; [95 percent ci, 0.262 - 0.907]; nominal p="0.0205)." an estimated 74.6 percent of previously untreated older and or comorbid patients were alive and progression-free at 3.5 years with i+v treatment compared to an estimated 24.8 percent of patients in the clb+o cohort. pfs at 3.5 years was higher for patients in the i+v arm compared to the clb+o arm for both unmutated ighv (uighv) and mutated ighv (mighv) cll. pfs was better sustained in the i+v arm compared to the clb+o arm, regardless of mrd (at least 10-4) status, measured at three months following end of treatment.></0.0001).>

Two years after end of treatment, estimated PFS was at least 90 percent for patients with mIGHV CLL, independent of MRD status, and for the 60 percent of patients with uIGHV CLL who achieved uMRD. uIGHV is a key prognostic and predictive factor associated with high-risk CLL that can help to predict disease outcomes and inform treatment choices. Updated data showed the safety profile of the I+V regimen was consistent with the known safety profiles of ibrutinib and venetoclax.

CLL is the most common form of leukaemia in the Western world and currently has no cure. While the treatment landscape has evolved significantly since the emergence of targeted agents, there is still significant unmet need for novel treatment options, including fixed-duration regimens. These results were highlighted in an oral presentation during the 2022 American Society of Hematology (ASH) Annual Meeting, taking place in New Orleans, U.S.