NICE Recommends Ibrutinib for Relapsed/Refractory MCL

The United Kingdom's National Institute for Health Care and Excellence (NICE) has published new guidelines recommending ibrutinib (Imbruvica) as treatment for patients with relapsed/refractory mantle cell lymphoma (MCL).

The BTK inhibitor is approved for patients who have undergone 1 previous line of therapy, and if Janssen Biotech, the drug’s manufacturer, provides ibrutinib “with the discount agreed in the commercial access agreement with NHS England.” The amount of the discount was not released.

Pharmacyclics LLC, an AbbVie company, and Janssen Biotech jointly developed and commercialized ibrutinib.

NICE concluded that the incremental cost-effectiveness ratios (ICERs) associated with ibrutinib for patients with relapsed/refractory MCL are above the range normally considered a cost-effective use of NHS resources of £20,000-£30,000, or $26,631-$39,947, per quality-adjusted life year (QALY) gained.

Earlier this year, NICE said it could not recommend routine use of ibrutinib in MCL because it did not meet NHS requirements for value per QALY. Ibrutinib is currently available through the Cancer Drugs Fund (CDF).

NICE is now recommending routine use of ibrutinib in the second-line setting, and has concluded that ibrutinib can be considered for end-of-life situations and estimates that its cost effectiveness is likely to be less than £49,848 ($66,376) per QALY gained.

Ibrutinib has been indicated for MCL in the United States since 2013.

AbbVie released data from a pooled analysis suggesting that ibrutinib can extend progression-free survival (PFS) in this patient population earlier this month at the 2017 ASH Annual Meeting. Overall, 53% (95% CI, 0.47-0.58) of patients treated with ibrutinib were alive at 2 years, 45% (95% CI, 0.39-0.50) were alive at 3 years, and 37% (95% CI, 0.25-0.49) were alive at 5 years. Median OS was 26.7 months.

Investigators examined data collected from the phase II SPARK and PCYC-114 studies, the phase III RAY trial, and the ongoing phase IIIb extension study CAN3001 (N = 370). Patients enrolled in SPARK, RAY, and PCYC-1104 received once-daily oral 560 mg of ibrutinib until progressive disease or unacceptable toxicity.

Patients in the SPARK, PCYC-1104, and RAY trials were required to have received at least 1 prior therapy for MCL and be chemotherapy-free for at least 3 weeks. Patients in SPARK were required to have already received rituximab (Rituxan) and bortezomib (Velcade), and patients in RAY were required to have already received rituximab. Patients who continued to benefit from ibrutinib therapy at the end of the studies were eligible to enroll in CAN3001.

At 41 months of follow-up, 36% (95% CI, 0.31-0.42) of patients assigned to ibrutinib were progression free at 2 years and 26% (95% CI, 0.20-0.32) were progression free at 3 years. Median PFS was 13 months. The median PFS in patients with 1 prior line of therapy was 33.6 months (range, 19.4-42.1).

More than one-quarter of patients (26.5%) achieved complete response (CR) while on treatment with ibrutinib. The median period for patients achieving CR was 46.2 months (range, 42.1-not estimable).

In the pooled analysis, the median duration of follow-up was 41.1 months (95% CI, 37.3-42.5) and median exposure to ibrutinib was 11.1 months (range, 0.03-72.1). Eighty-three patients were treated with ibrutinib for 3 or more years, and 40 patients were treated with ibrutinib for 4 or more years. Fifty-four of 87 patients (62.1%) enrolled in CAN3001 remain on ibrutinib.

Eight in 10 patients experienced grade ≥3 treatment-emergent adverse events (TEAEs). The most common grade ≥3 TEAEs were neutropenia (17.0%), thrombocytopenia (12.2%), pneumonia (11.9%), anemia (9.5%), atrial fibrillation (5.9%) and hypertension (5.1%). Most of these AEs were more common during the first year of ibrutinib treatment. Six in 10 patients experienced serious TEAEs. Cumulative incidence of any major hemorrhage was 7.3%. In all cases, incidence of TEAEs decreased after the first year.

“Imbruvica continues to provide a beneficial treatment option for patients with relapsed/refractory mantle cell lymphoma," Thorsten Graef, MD, PhD, head of clinical development, Pharmacyclics, said in a news release. “Prior to the discovery and introduction of Imbruvica, people diagnosed with MCL had limited treatment options. This long-term data analysis adds to our growing understanding of Imbruvica's potential treatment benefits for previously treated MCL patients.”

Rule S, Dreyling M, Goy A, et al. Median 3.5-year follow-up of ibrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: a pooled analysis. In: Proceedings from the 59th ASH Annual Meeting and Exposition; December 9-12, 2017; Atlanta, Georgia. Abstract 151.