Maintenance Ibrutinib Improves Efficacy in MCL

The primary end point for this study was to determine the 3-year PFS rate from the beginning of ibrutinib maintenance treatment. Secondary end points were to analyze toxicity, and assess partial response and CR rates.

Results from the phase 2 NU 14H06 study (NCT02242097) demonstrated efficacy in using ibrutinib (Imbruvica) maintenance for patients with mantle cell lymphoma (MCL) after induction chemotherapy, according to a press release from ObR Oncology.¹ 

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

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

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

During the study, patients received 560 mg of oral ibrutinib maintenance therapy daily for up to 4 years. Patients were evaluated monthly for the first 6 months and then every 3 months until termination of treatment. It was noted that 47% of patients (n = 17) completed full course ibrutinib maintenance at 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 treatment, and all patients have discontinued treatment.

The primary end point for this study was to determine the 3-year PFS rate from the beginning of ibrutinib maintenance treatment. Secondary end points were to analyze toxicity, and assess partial response and CR rates. Of note, the tertiary end point was to look at minimal residual disease (MRD) results by a polymerase chain reaction and measure with PFS and OS response.

Frequent adverse effects (AEs) were significant, according to the researchers. The most common treatment-related AE was infection (86%), which was typically low-grade. Other AEs included lymphopenia (81%), leukopenia (72%), diarrhea (67%), and thrombocytopenia (64%). Common AEs that were grade 3 or above were hematologic and included lymphopenia (58%) and neutropenia (36%). AEs caused temporary dose interruptions in 39% (n = 14) of patients and permanent dose reductions in 25% (n = 9) of patients.

Additionally, 42% (n = 15) of patients permanently discontinued ibrutinib maintenance treatment due to AEs, 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.

Studies assessing next-generation BTK inhibitors in early-line settings, such as the phase 3 SHINE (NCT01776840) and phase 2 WINDOW-01 (NCT02427620) studies, are being researched in order to potentially mitigate toxicity within treatment, according to researchers.^3,4

References

1. Rddad Y. Maintenance ibrutinib tied to overall survival in mantle cell lymphoma. News release. ObR Oncology. November 3, 2023. Accessed November 8, 2023. https://tinyurl.com/4uu9tcc2
2. Karmali R, Abramson JS, Stephens DM, et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023:bloodadvances.2023011271. doi:10.1182/bloodadvances.2023011271
3. Wang ML, Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. 2022;386(26):2482-2494. doi:10.1056/nejmoa2201817
4. Wang ML, Jain P, Zhao S, et al. Ibrutinib–rituximab followed by R-HCVAD as frontline treatment for 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