Ibrutinib maintenance therapy may improve the efficacy of MCL

According to a press release from ObR Oncology, results from the Phase 2 NU 14H06 study (NCT02242097) demonstrate the efficacy of maintenance therapy with ibrutinib (Imbruvica) following induction chemotherapy in patients with mantle cell lymphoma (MCL).¹

The median follow-up time was 55.7 months, the 3-year progression-free survival (PFS) rate was 94%, and the overall survival (OS) rate was 97%. For people who had previously received autologous stem cell transplantation (ASCT), the 3-year PFS and OS rates were 100% respectively.²

“It is clear that (Bruton’s tyrosine kinase (BTK)) inhibitors targeting mature B cells are effective in (MCL), and most of the data and approvals for various BTK inhibitors are in relapsed/refractory (MCL) Marc Braunstein, MD, a hematologist at NYU Langone Perlmutter Cancer Center (Long Island) and associate professor of medicine at NYU Grossman School of Medicine (Long Island), “The obvious next step is to study whether BTK inhibitors are effective in early production lines, particularly in the first-line and maintenance settings,” said the press release. “

This Phase 2 clinical trial included 36 patients with a mean age of 60 years (range: 46-90 years). Patients were required to have MCL and undergo at least 4 rounds of induction therapy, including rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP), hyperfractionated cyclophosphamide, vincristin Base, doxorubicin, and dexamethasone plus rituximab (R-HyperCVAD) or bendamustine in combination with rituximab (Rituxan), complete response (CR) or partial response to treatment (R-HyperCVAD) PR). Half of the population (n = 18) received ASCT consolidation therapy in first complete remission before starting ibrutinib maintenance therapy.

During the study, patients received maintenance therapy with 560 mg of oral ibrutinib daily for up to 4 years. Patients were evaluated monthly for the first 6 months and then every 3 months until treatment was discontinued. Of note, 47% of patients (n = 17) completed the full course of ibrutinib maintenance therapy with a median of 37.5 cycles (range 2-52). A total of 69% (n = 25) of patients completed at least 2 years of ibrutinib maintenance therapy, and all patients discontinued treatment.

The primary endpoint of this study was to determine the 3-year PFS rate from the start of ibrutinib maintenance therapy. Secondary endpoints were analysis of toxicity and assessment of partial response and CR rates. Of note, the tertiary endpoint was minimal residual disease (MRD) results observed by polymerase chain reaction and measured by PFS and OS responses.

The researchers stated that the frequent adverse events (AEs) were serious. The most common treatment-related AE was infection (86%), which was usually low-grade. Other adverse events included lymphopenia (81%), leukopenia (72%), diarrhea (67%), and thrombocytopenia (64%). Common AEs of grade 3 or higher were hematologic and included lymphopenia (58%) and neutropenia (36%). AEs resulted in temporary dose interruption in 39% (n = 14) of patients and permanent dose reduction in 25% (n = 9) of patients.

Additionally, 42% (n = 15) of patients permanently discontinued ibrutinib maintenance therapy due to adverse events such as pneumonia, myalgia, rash, pericardial effusion, mucositis, transient ischemic attack, and subdural hematoma. Grade 1/2 atrial fibrillation or flutter occurred in 28% (n = 10) of patients.

The researchers said studies evaluating next-generation BTK inhibitors in early-line settings, such as the Phase 3 SHINE (NCT01776840) and Phase 2 WINDOW-01 (NCT02427620) studies, are ongoing to potentially mitigate toxicities in treatment.^3.4

refer to

1. Rddad Y. Maintenance of ibrutinib is associated with overall survival in mantle cell lymphoma. Press Releases. ObR Oncology. November 3, 2023. Accessed 8 November 2023. https://tinyurl.com/4uu9tcc2
2. Karmali R, Abramson JS, Stephens DM, et al. Maintenance therapy with ibrutinib after first-line therapy in patients with mantle cell lymphoma. Blood Advance 2023: Bloody Progress.2023011271. doi:10.1182/bloodadvances.2023011271
3. Wang ML, Jurczak W, Jerkeman M, et al. Ibrutinib combined with bendamustine and rituximab for the treatment of untreated mantle cell lymphoma. New England Journal of Medicine 2022;386(26):2482-2494. doi:10.1056/nejmoa2201817
4. Wang ML, Jain P, Zhao S, et al. Ibrutinib plus rituximab plus R-HCVAD as first-line treatment in young patients (≤65 years) with mantle cell lymphoma (WINDOW-1): a single-arm phase 2 trial. Lancet Oncol. 2022;23(3):406-415. doi:10.1016/s1470-2045(21)00638-0