Time-limited therapy with the mix of acalabrutinib (Calquence) and obinutuzumab (Gazyva) led to responses in sufferers with treatment-naive persistent lymphocytic leukemia, in keeping with information from a section 2 trial (NCT04505254) introduced on the 2024 EHA Congress.1
Findings confirmed the general response fee (ORR) was 100% in efficacy-evaluable sufferers at 8 months (n = 21), 14 months (n = 15), and 24 months (n = 12). At 24 months, 67% of sufferers achieved a whole response (CR). Within the 12 sufferers who accomplished 24 cycles, 75% of sufferers remained in remission at a median follow-up of seven months following therapy discontinuation. Three of those sufferers skilled illness development, together with 1 who required retreatment.
“Ongoing correlative research and longer follow-up will outline which affected person traits are related to lengthy remissions after time-limited remedy with acalabrutinib plus obinutuzumab. This may increasingly assist outline for whom this remedy method may change into a substitute for present advice for steady remedy with BTK inhibitors,” lead research creator Jan A. Burger, MD, PhD, and colleagues, wrote in a poster presentation of the info.
Burger is a tenured professor within the Division of Leukemia, Division of Most cancers Drugs, at The College of Texas MD Anderson Most cancers Heart in Houston. He’s additionally the Privatdozent lecturer in inside medication on the Albert-Ludwigs College Faculty of Drugs in Freiberg, Germany.
The section 2, open-label, single-arm, single-center trial being performed at MD Anderson enrolled sufferers not less than 18 years of age with treatment-naive CLL or small lymphocytic lymphoma who had been indicated for therapy per 2018 Worldwide Workshop on CLL Standards. Sufferers had been required to have an ECOG efficiency standing of 0 to 2 and enough renal and hepatic operate.2
All enrolled sufferers (n = 28) obtained 100 mg of acalabrutinib twice per day beginning on day 1 of the primary 28-day cycle and continued for as much as 24 cycles. Obinutuzumab was given as a once-per-month infusion beginning in cycle 3 and continued for six cycles. Sufferers who achieved a CR after cycle 8 continued acalabrutinib monotherapy, and people with a partial response or steady illness obtained 6 further cycles of mixture remedy. Acalabrutinib was given as monotherapy after cycle 14 in all sufferers. All sufferers discontinued therapy after 24 cycles, and in sufferers who skilled illness development after discontinuing remedy, retreatment was allowed.1
The research’s major finish level was the sturdiness of treatment-free remissions following 24 cycles of remedy. Secondary finish factors embody evaluating the efficacy of retreatment and figuring out components related to extended remission.
The median affected person age of all enrolled sufferers was 65 years (vary, 40–83), and nearly all of sufferers had been male (61%). Per the Rai staging system, 4% of sufferers had low-risk illness, 39% had intermediate-risk illness, and 57% had high-risk illness. Fifty-seven % of sufferers harbored IGHV mutations. Different cytogenetics included 17p deletions (4%), 11q deletions (7%), trisomy 12 (25%), and 13q deletions (50%). Fourteen % of sufferers had regular cytogenetics. The median beta-2 microglobulin was 3.9 mg/L (vary, 2.2-9.6), and the median absolute lymphocyte depend was 35.9 Okay/µL (vary, 3.6-188.4).
At a median follow-up of 21 months, 25 sufferers (89%) remained on the research. One affected person died from bacterial pneumonia at cycle 3, and two others withdrew as a consequence of recurrent infections. The estimated two-year progression-free survival (PFS) and general survival (OS) charges had been 95.8%.
Bone marrow infiltration by CLL cells considerably decreased from a median of 84.2% at baseline to 0.1% after 24 cycles of remedy, and 4 sufferers achieved undetectable minimal residual illness.
References
- J. Burger, Kim E, Lopez W, et al. A section II research of time-limited therapy with acalabrutinib plus obinutuzumab in sufferers with treatment-naïve persistent lymphocytic leukemia. Introduced at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Summary P1841.
- Acalabrutinib and obinutuzumab for the therapy of persistent lymphocytic leukemia. ClinicalTrials.gov. Up to date April 2, 2024. Accessed July 24, 2024. https://clinicaltrials.gov/research/NCT04505254
