Combination Therapy Demonstrates Clinical, Economic Benefit in Certain Patients With CLL

Fixed-duration obinutuzumab-chlorambucil (G-CHL) treatment offered a marked clinical and economic benefit in patients with chronic lymphocytic leukemia (CLL) with mutated IGHV genes and those reaching undetectable measurable residual disease, according to study of real-world patients published in Frontiers in Oncology.

“The current frontline therapy of CLL patients can be either a continuous BTK inhibitor or a fixed-duration obinutuzumab-based therapy,” wrote researchers in Italy. “Choosing between the two approaches remains a challenge, since a continuous treatment might offer better disease control for some aggressive subsets of patients … [while] a fixed obinutuzumab-based therapy is administered for a short period, allowing the achievement of deep remission.” 

The retrospective study compared 183 previously untreated CLL patients without TP53 disruption from the Italian campus CLL network who were treated with the continuous BTK inhibitor ibrutinib (IB) or fixed duration G-CHL as first-line therapy. Patients who received G-CHL tended to have more comorbidities and worse renal function, researchers noted.

Overall response was similar for both treatments, although more patients achieved complete remission with G-CHL, according to the study. At follow-up a median 2.5 years later, progression-free survival and time to next treatment were better with IB compared with G-CHL, but overall survival — 91% for G-CHL and 96% for IB — was not. 

“While progression-free survival and time to next treatment were longer with IB than with G-CHL in IGHV unmutated patients (p = 0.0190 and 0.0137), they were superimposable for IGHV mutated patients (p = 0.1900 and 0.1380),” researchers reported.

Among patients treated with G-CHL, depth of response and measurable residual disease affected progression-free survival, the study showed. 

“Continuous treatment with IB provides longer remission in elderly CLL patients unfit for fludarabine-based therapy,” researchers concluded. “However, it is noteworthy that some patients can achieve long-term disease control with a less expensive fixed-duration obinutuzumab-based therapy, which may represent an option for first-line treatment in countries with economic constraints.”

Reference:
Visentin A, Mauro FR, Catania G, et al. Obinutuzumab plus chlorambucil versus ibrutinib in previously untreated chronic lymphocytic leukemia patients without TP53 disruptions: a real-life CLL campus study. Front Oncol. Published online November 21, 2022. doi:10.3389/fonc.2022.1033413