New follow-up data for IMBRUVICA® (ibrutinib) presented at ASH show longer term efficacy in patients with chronic lymphocytic Leukaemia and mantle cell lymphoma

The first set of data detailed a 16-month follow-up study¹ on the Phase 3 RESONATE™ trial, which showed IMBRUVICA significantly improved progression-free survival (PFS) and overall survival (OS) versus ofatumumab in patients with relapsed or refractory (RR) chronic lymphocytic leukaemia (CLL) regardless of baseline cytogenetics, or number of prior therapies. The second longer-term follow-up presentation reported two-year data from the Phase 2 PCYC-1104² study in patients with RR mantle cell lymphoma (MCL).

IMBRUVICA is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics Switzerland GmbH. Janssen affiliates market IMBRUVICA in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the United States, where Janssen Biotech, Inc. and Pharmacyclics, Inc. co-market it. 

In the RESONATE study with a median follow-up of 16-months,¹ the investigator-assessed PFS was significantly longer in patients with RR CLL receiving IMBRUVICA versus ofatumumab (median PFS not reached vs. 8.1 months respectively, an 89.4 percent reduction in the risk of progression or death [HR 0.106, 95 percent CI, 0.073-0.153, P<0.0001]). At 12 months, 84 percent of the IMBRUVICA patients continued progression-free compared to 19 percent in patients randomised to receive ofatumumab. The OS for patients randomised to receive IMBRUVICA was significantly longer than for patients in the ofatumumab arm, with 18-month survival rates of 85 percent versus 78 percent, despite 62 percent of ofatumumab patients crossing over to receive IMBRUVICA. The data were detailed in a poster presentation by Jennifer Brown, M.D., Ph.D., Director, Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute; Associate Professor of Medicine, Harvard Medical School on Sunday, December 7 [Abstract 3331].

“The investigator-assessed, progression-free survival rate in the IMBRUVICA RESONATE follow-up analysis clearly demonstrates the impact this treatment is already having on the lives of patients with relapsed or refractory chronic lymphocytic leukaemia,” said Brown.* “What was compelling about this study was IMBRUVICA improved progression-free survival, versus ofatumumab, regardless of baseline cytogenetics or number of prior therapies.”

In two-year follow-up data² from the PCYC-1104 study, IMBRUVICA was associated with a median PFS of 13 months and median OS of 22.5 months. Almost one-third of RR MCL patients (31 percent) remain progression-free at two years and almost half (47 percent) of the 111 patients in the study remain alive. The data were presented at ASH by Michael Wang, M.D., Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center and lead investigator for the pivotal registration trial PCYC-1104 on Monday, December 8 [Abstract 4453].

“The safety and efficacy over time seen with the use of single-agent IMBRUVICA in people with relapsed or refractory mantle cell lymphoma are very encouraging,” said Wang. † “These data further confirm the longer-term potential of IMBRUVICA as a treatment option, directly making a positive impact on our MCL patients.”

“The sustained responses seen in the longer-term treatment of patients with MCL and CLL are a positive development for people living with these rare and complex blood cancers,” said Thomas Stark Vice President Medical Affairs, Janssen Europe, Middle East and Africa (EMEA). “Janssen continues to work to better understand the full benefit of IMBRUVICA, and is encouraged by these results which demonstrate the potential of IMBRUVICA as an effective treatment option for both of these challenging blood cancers.”

Abstract 3331: Phase 3 RESONATE Follow-up¹

Sixteen-month follow-up data from the randomised, multicentre, open-label Phase 3 RESONATE trial (N=391), showed an investigator-assessed PFS at 12 months of 84 percent. After a median follow-up of 16 months, the investigator-assessed PFS was significantly longer in patients taking IMBRUVICA versus ofatumumab (not reached vs. 8.1 months [HR 0.106, 95 percent CI, 0.073-0.153, P<0.0001]). Treatment with ibrutinib demonstrates an 89.4 percent reduction in the risk of progression or death versus ofatumumab. The median OS in patients receiving IMBRUVICA has not yet been reached; the overall comparison showed OS for patients taking IMBRUVICA was significantly better than for patients in the ofatumumab arm, with 18-month OS rates of 85 percent and 78 percent respectively, despite 62 percent of patients randomised to ofatumumab who crossed over to receive IMBRUVICA and were censored at that time. The overall investigator-assessed response rate was 90 percent in patients taking IMBRUVICA (versus 25 percent in ofatumumab patients; P<0.0001), including eight percent of patients who achieved a partial response with lymphocytosis.

In an exploratory analysis, Brown showed that patients who had received only one versus two or more prior therapies before IMBRUVICA had a higher PFS (94 percent at 12 months versus 82 percent; P=0.01). An additional analysis also showed the rates of ORR and PFS were similar in patients with or without del17p, indicating that the high risk del17p mutation did not confer a worse outcome for patients receiving IMBRUVICA.

Overall, at a median follow-up of 16 months, seventy-six percent of people randomised to IMBRUVICA continued on treatment in the study.

There were no new safety findings with the most common Grade 3 or 4 AEs in the RESONATE trial analysis (occurring in five percent or more of IMBRUVICA patients) were neutropenia (18 percent), pneumonia (9 percent), thrombocytopenia (low platelets in the blood; 6 percent), anaemia (6 percent) and hypertension (6 percent). The most frequently reported AEs of any grade were diarrhoea (37 percent), nausea (24 percent), fatigue (18 percent) and atrial fibrillation (7 percent). Forty-seven people (24 percent) discontinued IMBRUVICA: 17 due to progressive disease (9 percent), 13 due to AEs (7 percent) and 10 (5 percent) due to death. Notably, the incidence of treatment-emergent AEs decreased over time.

Abstract 4453: 2-year follow-up of IMBRUVICA in relapsed/refractory MCL²

Patients in the Phase 2 multicentre, open-label, PCYC-1104 study received 560mg IMBRUVICA once daily until disease progression or unacceptable toxicity, and were eligible to continue on therapy via a long-term extension study (N=111 treated patients). Fifty-one patients (46 percent) were treated for more than one year and 29 patients (26 percent) who continued on treatment and follow-up in the extension study were treated for more than two years. Importantly, two-year (median of 26.7 months) follow-up data from the trial confirmed nearly one-third of patients (31 percent) were still progression-free and almost half of the 111 treated patients (47 percent) remain alive today. The median PFS was 13 months and the median OS was 22.5 months. Investigator-assessed ORR (primary endpoint) was 67 percent, with a complete response (CR) in 22.5 percent of patients. Additionally, the median time to response was 1.9 months.

The most common Grade 3 or greater adverse events (AEs) in the study were infection (28 percent), diarrhoea (5 percent) and bleeding (6 percent). Grade 3 or greater AEs occurred in 81 percent of people and serious AEs (SAEs) of any grade occurred in 63 percent of patients. The most frequently reported (occurring in >30 percent of IMBRUVICA patients) AEs of any grade were infection (78 percent), diarrhoea (54 percent), bleeding (50.5 percent), fatigue (49.5 percent), nausea (33 percent) and dyspnoea (shortness of breath; 32 percent). Treatment discontinuation due to AEs was reported in 11 percent of patients.

1. Brown J et al. ASH abstract 3331: Updated Efficacy Including Genetic and Clinical Subgroup Analysis and Overall Safety in the Phase 3 RESONATE™ Trial of Ibrutinib Versus Ofatumumab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
2. Wang M et al. ASH abstract 4453: Single-Agent Ibrutinib Demonstrates Safety and Durability of Response at 2 Years Follow-up in Patients with Relapsed or Refractory Mantle Cell Lymphoma: Updated Results of an International, Multicenter, Open-Label Phase 2 Study.